Patent Application
20140128784
Various aspects of the present invention are generally directed to isometric exercise and a system, method, and apparatus for isometric exercise, and more specifically to the use of the system, method, and apparatus for isometric exercise to treat various conditions.
This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present invention, which are described and/or claimed below. This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of various aspects of the present invention. Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.
The use of isometric exercise, as opposed to rhythmic exercise, in the general field of athletic strength development, as well as a therapy for strength recovery, has been the subject of somewhat controversial discourse over the past decades. In general, isometric exercise has been considered to promote coronary risk factors (among other deleterious effects) [See generally: Vecht R J, Graham G W S, Sever P S. “Plasma Noradrenaline Concentrations During Isometric Exercise.” Brit Heart J. 1978; 40:1216-20; and Chrysant S G. “Hemodynamic Effects of Isometric Exercise in Normotensive Hypertensive Subjects”: Hypertension. Angiology 1978:29(5):379-85].
Because isometric exercise was thought to promote coronary risk factors, it was generally not considered useful in treating conditions such as hypertension and other conditions that may include a condition of the circulatory system, such as erectile dysfunction, type II diabetes, obesity, etc. Indeed, in many of these cases, isometric exercise was thought of as being contraindicated.
Hypertension (also known as high blood pressure) is a chronic medical condition in which the blood pressure in the arteries is elevated, thereby causing the heart to work harder than normal to circulate blood through the body. Hypertension is associated with an increased risk of a wide range of disease and disorder, including stroke, organ failure, and cardiopathy. Risk factors for hypertension include obesity, genetic factors, smoking, diet, and inactivity.
Erectile dysfunction (ED) is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis. Stimulation of penile shaft by the nervous system leads to the relaxation of smooth muscles of corpora cavernosa (the main erectile tissue of penis) and the inflow of blood to that tissue, which results in penile erection. Impotence may develop due to a lack of adequate penile blood supply, and so there may be various circulatory causes of ED. For example, restriction of blood flow can arise from impaired endothelial function due to the usual causes associated with coronary artery disease. Diabetes may be another cause of ED.
Diabetes mellitus type 2 (“type 2 diabetes,” also known as non-insulin-dependent diabetes mellitus or adult-onset diabetes) is a metabolic disorder that is characterized by high blood glucose, insulin resistance, and relative insulin deficiency. Obesity is thought to be one primary cause of type 2 diabetes in people who are genetically predisposed to the disease.
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems. Body mass index (BMI), a measurement which compares weight and height, presently defines people as overweight (pre-obese) if their BMI is between 25 and 30 kg/m2, and obese when it is greater than 30 kg/m2. Obesity increases the likelihood of various diseases, such as heart disease and type 2 diabetes. Obesity is most commonly caused by a combination of excessive food energy intake, lack of physical activity, and genetic susceptibility.
Hypertension, hypercholesterolemia, atherosclerosis and cardiovascular disease are interrelated in their causes, treatment and effect on the body (and, as can be seen from the discussion above, ED, diabetes, and obesity may also have interrelated causes—or be the cause of one another, as well as with hypertension). The class of drugs known as HMG-CoA reductase inhibitors or statins is widely prescribed for treatment of hypercholesterolemia and associated cardiovascular disease, including the debilitating effects of progressive atherosclerosis. Various statins that have been clinically utilized include atovastatin, cerivastatin, fluvastatin, ovastatin simvastatin among others. The statin drugs were initially prescribed to relieve hypercholesterolemia, and to reduce the blood concentrations of low-density lipoprotein (LDL) and triglycerides. It has become apparent that the statin drugs apparently have additional therapeutic benefits that are independent and or interrelated with the effects of reduction in blood cholesterol concentration. The effect of statin drugs thus includes a reduction in vascular inflammation, and a protection of the heart against ischemic disorders. [For more information on the pleiotropic effects of the statin drugs see generally: Davignon J., Beneficial cardiovascular pleiotropic effects of statins, Circulation, 109 (23 Suppl 1):11139-43 (2004); Elrod J W, Lefer D J The effects of statins on endothelium, inflammation and cardioprotection, Drug News Perspect, 18(4):229-36 (2005, May); Assanasen C, et al., Cholesterol binding, efflux, and a PDZ-interacting domain of scavenger receptor-BI mediate HDL-initiated signaling, J Clin Invest., 115(4):969-77 (2005 April).]
Although the exact mechanism of statin drug action for cardioprotection is not fully known, it is widely believed that statin drugs stimulate nitric oxide synthase activity in vascular endothelium, and presumably in other tissues. Disorders of the vascular endothelium related to nitric oxide metabolism are believed to play a crucial role in the pathogenesis of atherosclerosis in hypercholesterolemia. Thus, certain cardioprotective effects of statin drugs can be mimicked in part by other physiological stimuli that induce nitric oxide synthase and increase nitric oxide availability. Moreover, nitric oxide metabolism is interconnected with the metabolism and regulation of LDL, cholesterol and triglycerides, and with the progress of atherosclerosis. As one example of this interrelationship, changes in nitric oxide levels have been inversely correlated with changes in LDL-cholesterol concentrations.
Nitric oxide (NO) has been identified as a signaling molecule in mammalian and other systems. NO, is a labile, endogenously produced gas that is enzymatically synthesized, can rapidly diffuse, and quickly disappear. NO is known to be a potent regulator of blood pressure due to its activity as a vasodilator, but has a diverse action on a wide variety of organ systems. Endothelial nitric oxide synthase (eNOS) is induced to synthesize NO by blood vessel wall shear stress. Upon the activation of eNOS and induction of NO synthesis, NO is released by endothelial cells. Based on the position of endothelial cells lining the inner surface of blood vessels, NO can be released into the blood stream, where it can act both locally and systemically. NO induces vasodilation by a reduction in the contraction of smooth muscle cells lining blood vessels. NO acts as a negative feedback for mean arterial pressure, since as arterial pressure increases, wall shear stress increases, inducing eNOS and increasing the NO concentration. As NO concentration increases, smooth muscle contraction is decreased, blood vessel lumen diameter increases, arteriole resistance decreases and arterial pressure decreases. The modulating action of wall shear stress on eNOS activity and NO production serves to maintain wall shear stress at a constant level. A diagram highlighting some of the interactions between NO, local metabolites, wall shear stress and smooth muscle contraction is shown in
Prolonged elevation of wall shear stress, in addition to activation of eNOS, leads to the transcriptional activation of the eNOS gene in endothelial cells. After several hours, eNOS enzyme levels increase due to the induced transcription of the eNOS gene. Increased levels of eNOS enzyme in endothelial cells increases those cells ability to release NO following induction of eNOS activity. It is thus expected that those cells which have experienced prolonged elevation of wall shear stress will have an increased ability to synthesize NO, and the same levels of wall shear stress will result in a greater synthesis of NO. One effect of increased eNOS levels is a reduction in the amount of wall shear stress that is required to induce biologically significant NO levels. Blood vessels that have been entrained by prolonged elevation of wall shear stress will release more NO relative to shear stress, and the vasodilation effect of NO will be increased, Higher relative NO concentration leads to reduced smooth muscle contraction, increased blood vessel lumen diameter and decreased arteriole resistance. Assuming that the cardiac output of the heart does not change, the net effect of a lower “set point” for responding to wall shear stress is a reduction in total peripheral resistance in blood vessels and a reduction in mean arterial pressure.
Similar to the effects of the statin drugs, an improvement in endothelial function is interconnected with LDL and cholesterol blood levels and NO bioavailability. LDL and cholesterol have been shown to prevent the down-regulation of eNOS. In turn, down-regulation of eNOS is apparently mediated by the stimulation of levels of caveolin-1 by LDL. Caveolin-1 is an important inhibitor of eNOS catalytic activity. Modulation of NO is expected to affect the interrelated blood lipid concentrations of VHDL, HDL, LDL, and cholesterol. To the extent that the pleiotropic activity of the cholesterol lowering statin drugs is modulated by NO levels, stimulation of NO bioavailability is expected to affect blood lipid composition. For additional background on the interrelationship between LDL and NO, see generally: Martinez-Gonzalez, J., et al., Arterioscler. Thromb. Vasc. Biol. 21: 804-809 (2001).
As described above, it has been known for some time that exercise can provide relief from hypertension in certain individuals. As the modulation of nitric oxide levels is part of a feedback system that responds in part to the stretching and extensibility of blood vessels of the body, it is hypothesized that exercise in general plays a role in stimulating cycles of NO release, and effectively providing some of the benefits of statin drugs, including improvement in endothelial function, increased nitric oxide bioavailability, anti-oxidant effects, anti-inflammatory protection, and stabilization of atherosclerotic plaques. Notwithstanding the effects of the modulation of NO bioavailability, exercise is known to modulate blood cholesterol and blood lipid composition.
However, as also stated above, previous conventional wisdom would suggest that isometric exercise would be ineffective in treating such conditions (as opposed to rhythmic or dynamic exercise), due to the belief that isometric exercise promotes coronary risk factors (among other deleterious effects). And so, rhythmic or dynamic exercise is primarily used as a therapy for various conditions (rather than isometric exercise).
Certain exemplary aspects of the invention are set forth below. It should be understood that these aspects are presented merely to provide the reader with a brief summary of certain forms the invention might take and that these aspects are not intended to limit the scope of the invention. Indeed, the invention may encompass a variety of aspects that may not be explicitly set forth below.
One aspect of the present invention includes a system and method of using isometric exercise to treat various conditions, including erectile dysfunction, type 2 diabetes, and obesity. In general, the system includes applying a force to an isometric exercising mechanism via an elected exercisable muscle group of the musculature of a user. The mechanism is responsive to the force applied, and the application of force increases shear stress on a blood vessel wall of the user. This induces the synthesis of endothelial nitric oxide synthase, which results in synthesis of NO in the user, thereby increasing the amount of bioavailable NO in the user. In certain embodiments, through the selection of the particular muscle group used, or through the particular exercise protocol, or any combination, a therapy for a particular condition (e.g., ED, obesity, or diabetes) may be provided.
Another aspect of the present invention provides an apparatus for carrying out a controlled isometric regimen by a user. In one exemplary embodiment, the apparatus may include a handgrip-based dynamometer. Being microprocessor driven, the instrument is programmed to carry out established diagnostic as well as newly developed grip-based isometric regimens. When employed for carrying out a diagnostic maximum grip test, the diagnostician selects configuration parameters and the instrument provides both visual and audible prompts and cues throughout the procedure. Maximum grip forces for each of the sequence of trials of this procedure are selected typically by the diagnostician and when so selected are recorded in instrument memory along with calendar data, and processor computed values for average grip force, standard deviation of the force values throughout a sequence of tests and corresponding coefficients of variation. At the termination of the diagnostic procedure, memory recorded test data are displayable to the diagnostician and may be downloaded through a communications port to a computer facility.
When used for a therapeutic purpose, use of the apparatus begins with a determination of the maximal isometric force which can be exerted by a patient with any given muscle (e.g., skeletal muscle or group of muscles) of such patient. The determined maximal isometric force is recorded. The patient, then, is periodically permitted to intermittently engage in isometric contraction of the given muscle at a fractional level of the maximal force determined for a given contraction duration followed by a given resting duration. A perceptible indicia correlative to the isometric force exerted by the given muscle is displayed to the patient so that the patient can sustain the given fractional level of maximal force.
As described above, it has been known for some time that exercise can provide relief from hypertension in certain individuals. As the modulation of nitric oxide levels is part of a feedback system that responds in part to the stretching and extensibility of blood vessels of the body, it is hypothesized that exercise in general plays a role in stimulating cycles of NO release, and effectively providing some of the benefits of statin drugs, including improvement in endothelial function, increased nitric oxide bioavailability, anti-oxidant effects, anti-inflammatory protection, and stabilization of atherosclerotic plaques. Notwithstanding the effects of the modulation of NO bioavailability, exercise is known to modulate blood cholesterol and blood lipid composition.
However, as also stated above, previous conventional wisdom would suggest that isometric exercise would be ineffective in treating such conditions (as opposed to rhythmic or dynamic exercise), due to the belief that isometric exercise promotes coronary risk factors.
In addition to the coronary risk factors believed to be promoted by isometric exercise, early subjects or trainees undergoing isometric exercise stressed the involved musculature to their full or maximum capability (Kiveloff, et al., “Brief Maximal Isometric Exercise in Hypertension”, J. Am. Geriatr. Soc., 9:1006-1012, 1971) or at some submaximal force as long as it could be sustained, in either case only terminating with the onset of unendurable fatigue. Such approaches often have incurred somewhat deleterious results as evidenced by the injuries sustained in consequence of improper weightlifting procedures. Weightlifting procedures or endeavors exhibit a significant isometric factor. See generally: Lind A R. “Cardiovascular Responses to Static Exercise” (Isometrics, Anyone?) Circulation 1970:41(2):173-176; and Mitchell J H, Wildenthal K. “Static (Isometric) Exercise and the Heart: Physiological and Clinical Considerations”. Ann Rev Med 1974; 25:369-81.
However, as such attitudes persisted, some investigators commenced to observe contradictions to these generally accepted beliefs. See for, example, the following publications: Buck, et al., “Isometric Occupational Exercise and the Incidence of Hypertension”, J. Occup. Med., 27:370-372, 1985; Choquette. et al., “Blood Pressure Reduction in ‘Borderline’ Hypertensives Following Physical Training” Can. Med. Assoc. J. 1108:699-703, 1973; Clark, et al., “The Duration of Sustained Contractions of the Human Forearm of Different Muscle Temperatures”, J. Physiol., 143:454-473, 1958; Gilders, et al., “Endurance Training and Blood Pressure in Normotensive and Hypertensive Adults”, Med. Sci. Sports Exerc. 21:629-636, 1989; Hagberg, et al., “Effect of Weight Training on Blood Pressure and Hemodynamics in Hypertensive Adolescents”, J. Pediatr. 1104:147-151, 1984; Harris, et al., “Physiological Response to Circuit Weight Training in Borderline Hypertensive Subjects”, Med. Sci. Sports Exerc., 19:246-252, 1987; Hurley, et al., “Resistive Training Can Induce Coronary Risk Factors Without Altering Vo.sub.2 max or Percent Body Fat” Med. Sci. Sports Exerc. 20:150-154, 1988; Hypertension Detection and Follow-up Program Cooperative Group, “The Effect of Treatment on Mortality in ‘Mild’ Hypertension”, N. Engl. J. Med., 307:976-980, 1982; Kiveloff, et al., “Brief Maximal Isometric Exercise in Hypertension”, J. Am. Geriatr. Soc., 9:1006-1012, 1971; Merideth et al., “Exercise Training Lowers Resting Renal but not Cardiac Sympathetic Activity n Humans”, Hypertension, 18:575-582, 1991; Seals and Hagberg, “The Effect of Exercise Training on Human Hypertension: A Review”, Med. Sci. Sports Exerc. 16:207-215, 1984; and Hanson P. Nagle F. “Isometric Exercise: Cardiovascular Responses in Normal and Cardiac Populations.” Cardiology Clinics 1987; 5(2): 157-70. Such speculation on the part of these early observers was confirmed by Wiley, and was taken further by Wiley in the 1990s as a possible treatment for hypertension, as described in U.S. Pat. No. 5,398,696 entitled “Isometric Exercise Method for Lowering Resting Blood Pressure and Grip Dynamometer Useful Therefore”, issued Mar. 21, 1995 and as described in the following publication: Wiley, et al., “Isometric Exercise Training Lowers Resting Blood Pressure”, Med. Sci. Sports Exerc. 29:749-754, 1992 incorporated by reference herein in its entirety.
With the approach of protocol developed by Wiley, the isometric regimen is closely controlled both in terms of exerted force and in the timing of trials or exertions. The system and method described by Wiley are known to be useful for treating hypertension. Hypertension is associated with an increased risk of a wide range of disease and disorder, including stroke, organ failure, and particularly cardiopathy. The exact causes of hypertension are rarely known with certainty, but risk factors for hypertension include obesity, genetic factors, smoking, diet and inactivity. As Wiley has shown, not all forms of exercise provide equivalent therapeutic benefit to the cardiovascular system and for the treatment of hypercholesterolemia, with a protocol for brief maximal isometric exercise providing a clear benefit.
In about 1998, the above-noted Wiley protocols as described in connection with Merideth et al., “Exercise Training Lowers Resting Renal but not Cardiac Sympathetic Activity n Humans”, Hypertension, 18:575-582, 1991, were incorporated in a compact, lightweight isometric device. This device was a hand-held dynamometer. The diagnosis of patient hand-arm strength using isometric-based testing has been employed by physiologists, physical therapists and medical personnel for over three decades. These procedures function to evaluate hand-arm trauma or dysfunction and involve the patient use of a handgrip-based dynamometer. The dynamometer is grasped by the patient and squeezed to a maximum capability under the verbal instruction of an attending therapist or diagnostician. The hand dynamometer most widely used for these evaluations incorporates a grip serving to apply force through closed circuit hydraulics to a force readout provided by an analog meter facing outwardly so as to be practitioner readable. Adjustment of the size of the grip of the dynamometer is provided by inward or outward positioning of a forwardly disposed grip component. The dynamometers currently are marketed under the trade designation: “Jamar Hydraulic Hand Dynamometer” by Sammons Preston of Bolingbrook, Ill. An extended history of use of these dynamometers has resulted in what may be deemed a “standardization” of testing protocols. For instance, three of the above-noted grip length adjustments are employed in a standardized approach and verbal instructions on the part of the testing attendant, as well as the treatment of force data read from the analog meter are now matters of accepted protocol. In the latter regard, multiple maximum strength values are recorded whereupon average strengths, standard deviations and coefficients of variation are computed by the practitioner. In one test, the instrument is alternately passed between the patient's right and left hands to derive a maximum strength output reading each 1.5 seconds or 2.5 seconds. Reading and hand recording strength values for such protocols has remained problematic. The protocols, for example, have been the subject of recommendations by the American Society of Hand Therapist (ASHT) and have been discussed in a variety of publications including the following: Mathiowetz V., Federman S., Wiemer D. “Grip and Pinch Strength: Norms for 6 to 19 Year Olds.” The American Journal of Occupational Therapy 40:705-11, 1986; Mathiowetz V., Donohoe L., Renells C. “Effect of Elbow Position on Grip and Key Pinch Strength.” The Journal of Hand Surgery 10A;694-7, 1985; Mathiowetz V., Dove M., Kashman N., Rogers S., Volland G., Weber K. “Grip and Pinch Strength: Normative Data for Adults.” Arch Phys Med Rehabilitation 66:69-72, 1985; and Mathiowetz V., Volland G., Kashman N., “Reliability and Validity of Grip and Pinch Strength Evaluations.” The Journal of Hand Surgery 9A:22-6, 1984.
Described in detail in U.S. Pat. No. 5,904,639 entitled “Apparatus, System, and Method for Carrying Out Protocol-Based Isometric Exercise Regimens” by Smyser, et al., the hand-held dynamometer has a hand grip which incorporates a load cell assembly. Extending from the hand grip is a liquid crystal display and two user actuated control switches or switch buttons. The display is mounted in sloping fashion with respect to the grip such that the user can observe important visual cues or prompts while carrying out a controlled exercise regimen specifically structured in terms of force values and timing in accordance with the Wiley protocols. This device is therapeutic as opposed to diagnostic in nature and is microprocessor driven with archival memory. External communication with the battery powered instrument is made available through a communications port such that the device may be configured by programming and, additional data, such as blood pressure values and the like may be inserted into its memory from an external device. Visual and audible cueing not only guides the user through a multi-step protocol but also aids the user in maintaining pre-computed target level grip compression levels.
This described apparatus, incorporating the protocol of Wiley, provided a system for treating hypertension. However, while Wiley has previously shown the possible benefits of isometric exercise in the treatment of hypertension, there still is lacking a similar treatment for afflictions such as ED, diabetes, and obesity.
To that end, there is widespread discourse on the relative benefits of particular forms of exercise, and there is an ongoing need for patients suffering from hypertension, hypercholesteremia, atherosclerosis, and other cardiovascular and cardiopulmonary diseases, as well as ED, diabetes, and obesity to be provided a therapeutic treatment, and to obtain the maximum benefit from the exercise utilized. Patients who are suffering from severe cardiovascular disease may be unable to engage in intense exercise, and many patients may be unable to engage in other forms of exercise due to limitations in time or facility availability. The invention disclosed herein provides for a device, system and method of exercise that can be optimized to provide an improved benefit to the patient in stimulating endothelial function, overall blood vessel health, and cardiovascular benefit while at the same time limiting the dangerous side effects of intensive exercise. Thus, aspects of the present invention provide for the treatment of hypertension via isometric exercise. Aspects of the present invention also provide for treatment of ED, diabetes, and obesity via isometric exercise (which was heretofore nonexistent).
Of course, it will be beneficial to incorporate improved diagnostic features for hand-arm evaluation techniques with therapist or practitioner designed therapeutic protocols specifically tailored to the condition of a given patient and which provide a control over such therapies clearly establishing such therapies as beneficial to strength development and recovery. One particular diagnostic and therapeutic feature that would be beneficial to incorporate is protocol that modulates wall shear stress of blood vessels so as to increase the bioavailability of nitric oxide and foster a reduction in total peripheral resistance in blood vessels and a reduction in mean arterial pressure, along with the other physiologic benefits associated with stimulation of NO signaling pathways, including reduction in LDL and cholesterol concentrations and an increase in arterial flexibility. Such a device could also be used with protocols designed to treat other conditions, such as ED, obesity, and diabetes.
For each of the diagnostic procedures, the widthwise extent of the instrument grip may be both varied in standard ½ inch increments from a minimum width. The grip is further configured such that the visually perceptible readout of the instrument may be viewed only by the diagnostician where deemed appropriate.
An important aspect of the therapeutic method associated with the instrument of the invention resides in the limiting of user performance to carry out the regimen of trials. In this regard, the instrument is programmed to perform only within predetermined and mandated test limits. Each therapeutic regimen is based upon an initial evaluation of the maximum gripping force capability of the user. Under that limitation, target load factors, hold on target load intervals, intervening rest intervals and trial repetition numbers may be elected only from pre-established and mandated memory retained ranges. The program also nominates rest intervals and hold on target intervals in correspondence with user elected target force factors. Thus, valuable strength recovery and development may be achieved but only within safe limits.
During each of the above therapeutic regimens, an audible warning is elicited whenever the user grip force value exceeds a computed upper limit. During each timed interval wherein the user is prompted to grip at a target force value computed with respect to the pre-tested maximum grip force, a dynamic bar graph and center point display is provided as a visual cue related to desired grip performance. Additionally, a rapid succession of score values are computed and the average thereof recorded at the end of each trial of a given regimen. These scores permit a therapist to access the quality of the performance of the user. In general, trial data is recorded in conjunction with calendar data and, as before, may be downloaded to a computer facility from an instrument contained communications port.
An additional aspect of the invention is to influence biological parameters of the user by selecting target loads that stimulate particular biological pathways. In one target force mode, the invention allows stimulation of nitric oxide bioavailability, which directly influences resting blood pressure and overall cardiovascular health. In other instances, the target force mode can be directed to maximize the exercise benefit for modulating blood lipid composition, including reducing low density lipoprotein (LDL) and cholesterol in the blood. The system, method, and apparatus described herein also provide for treatment of various other conditions, such as erectile dysfunction, obesity, and type II diabetes.
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with the general description of the invention given above and the detailed description of the embodiments given below, serve to explain the principles of the present invention.
One or more specific embodiments of the present invention will be described below. In an effort to provide a concise description of these embodiments, all features of an actual implementation may not be described in the specification. It should be appreciated that in the development of any such actual implementation, as in any engineering or design project, numerous implementation-specific decisions must be made to achieve the developers' specific goals, such as compliance with system-related and business-related constraints, which may vary from one implementation to another. Moreover, it should be appreciated that such a development effort might be complex and time consuming, but would nevertheless be a routine undertaking of design, fabrication, and manufacture for those of ordinary skill having the benefit of this disclosure.
One aspect of the present invention includes a system and method of using isometric exercise to treat various conditions, including erectile dysfunction, type 2 diabetes, and obesity. In general, the system includes applying a force to an isometric exercising mechanism via an elected exercisable muscle group of the musculature of a user. The mechanism is responsive to the force applied, and the application of force increases shear stress on a blood vessel wall of the user. This induces the immediate release of increased amounts of NO, and the increased synthesis of endothelial nitric oxide synthase, which results in longer term increased synthesis of NO in the user, thereby increasing the amount of bioavailable NO in the user. In certain embodiments, through the selection of the particular muscle group used, or through the particular exercise protocol, or any combination, a therapy for a particular condition (e.g., ED, obesity, or diabetes) may be provided.
Another aspect of the present invention provides an apparatus for carrying out a controlled isometric regimen by a user. In one exemplary embodiment, the apparatus may include a handgrip-based dynamometer. Being microprocessor driven, the instrument is programmed to carry out established diagnostic as well as newly developed grip-based isometric regimens. When employed for carrying out a diagnostic maximum grip test, the diagnostician selects configuration parameters and the instrument provides both visual and audible prompts and cues throughout the procedure. Maximum grip forces for each of the sequence of trials of this procedure are selected typically by the diagnostician and when so selected are recorded in instrument memory along with calendar data, and processor computed values for average grip force, standard deviation of the force values throughout a sequence of tests and corresponding coefficients of variation. At the termination of the diagnostic procedure, memory recorded test data are displayable to the diagnostician and may be downloaded through a communications port to a computer facility.
The isometric exercise apparatus under which the methodology of the invention may be carried out is lightweight, portable, battery powered and sufficiently rugged to withstand the compressive pressures which it necessarily endures during use. The instrument is programmable such that it may be utilized by a therapeutic practitioner for diagnostic purposes employing established grip test modalities. Strength measurements carried out during these modes are compiled in memory and the practitioner is afforded calculated values for average grip force, standard deviation and coefficient of variation with respect to grip force trials. Furthermore, individual strength measurements compiled in these averages, whether taken rapidly or slowly, are stored in memory and may be reviewed by the therapist.
Additionally, the instrument is employable as a therapeutic device. First a protocol is nominated by prescribing nominal parameters of the effort. Each isometric regimen is controlled initially by requiring that a maximum grip strength be established for each individual patient or user. Then, the practitioner may elect parameters of grip force and timing under mandated memory contained parameter limits. Accordingly, the user will be unable to carry out strength enhancement therapies which would otherwise constitute an excessive grip force regimen. For carrying out the noted diagnostic procedures as well as therapy activities, the grip widthwise extent is variable from 1.875 inches to 2.875 inches, such variation being adjustable in ½ inch increments. This is in keeping with standardized diagnostic practices. Further with respect to diagnostic procedures, the display or readout of the instrument can be adjusted with respect to the grip structuring such that only the practitioner or therapist may observe the data which is being developed during a diagnostic protocol.
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Referring to
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Disposed centrally within the cavity defined by gripping portion sides 52 and 54 is a steel thrust plate 82 having a thickness and rigidity elected to withstand compressive gripping forces which may range, for example, up to about 205 pounds. Plate 82 is configured with two holes 81 and 83 which are used to restrain the plate from disengaging from the assembly when fitted over respective posts 53 and 55. Elongate side 84 of thrust plate 82 is configured for insertion within an elongate groove 86 of a base grip component 88. Grip component 88 is formed of a rigid plastic and includes an outwardly disposed base grasping surface 90 upwardly located in adjacency with the grasping surface 90 is one component of a base connector assembly represented generally at 92 and which is seen to be integrally molded with the grip component 88 and incorporates a slot or opening 94 in conjunction with a tab receiving trough 96. A tab component (not shown) of the base connector assembly feature of the base grip component 88 will be seen to extend from the end thereof opposite connector assembly component 92.
Two oppositely disposed edge extensions 98 and 100 of the trust plate 82 are configured for operative association with a load cell assembly represented generally at 102. Load cell assembly 102 includes an elongate steel base 104 incorporating two slots for receiving extensions 98 and 100, one such slot being revealed at 106. Connection between the base 104 and thrust plate 82 is provided by pins (not shown) which extend through mated bores 108 and 110 and 112 and 114. The load cell assembly 102 further includes an elongate outer force component 116. Two field plate-form load cells 118 and 120 are mounted from load cell mount structures shown, respectively at 122 and 124 formed within base 104. Such mounting is in cantilever fashion, the load cell 118 being attached to mount 122 by a screw and mounting plate assembly 126. Similarly, load cell 120 is attached in cantilever fashion to mount structure 124 by a screw and mounting plate assembly 128. Outer force component 116 is seen to have a centrally disposed rectangular post portion 120 which is attached by a connector plate assembly to the mutually inwardly extending ends of the load cells 118 and 120. the attachment plate assembly for this union is seen in general at 132. Assembly 132 is seen to be formed of two plate components 132a and 132b coupled, in turn, to load cells 120 and 118. Screws are used to effect the attachment.
The base grip component positioned oppositely of base grip component 88 is shown at 134. In similar fashion as component 88, the base grip component 134 is configured with a base connector assembly having one component at 136 which incorporates a slot and trough (not shown) in similar fashion as described at 92 in connection with component 88. a tab protrusion of generally cylindrical configuration shown at 138 is disposed oppositely from connector assembly component 136. The rigid plastic base component 134 is attached to elongate outer force component 116 of the load cell assembly 102. This attachment is provided by the insertion and crimping of two posts 134a and 134b (
Auxiliary grip component 34 is shown in the figure in spaced adjacency with respect to the base grip component 134. Auxiliary component 34 is configured with an outwardly disposed auxiliary grasping surface of generally half cylindrical cross section with a grasping surface profile curved concavely outwardly, for example, at region 140. This curvature is provided for enhancing grip contact with the palm of the user hand and for applying force centrally to the load cell assembly. Component 34 is formed with an auxiliary connector assembly which includes a flexible engaging tab 150 configured for insertion within the connector component 136 of base grip component 134. Connection at the opposite end is provided by a curved slot (not shown) which receives the tab protrusion 138 of base grip component 134. The connector assemblies are universal such that each of the auxiliary grip components may be mounted upon either of the base grip components 88 or 134. In this regard, not that a similar flexible engaging tab 152 is positioned upwardly upon auxiliary grip component 36. Similarly, the component 36 is configured having a curved slot 154 at its opposite end which receives tabs, for example, as at 138. The mounting of either auxiliary grip component 36 or 34 will increase the widthwise extent of the grip by one half inch. Accordingly, with both auxiliary grip components installed, the widthwise extent of the grip is increased to 27/8 inches.
Interacting region 16 also includes a top cover 156. Formed, as the other components, of ABS plastic, the cover 156 includes a rectangular bezel opening 158 within which the LCD 18 is positioned. Integrally formed with top cover 156 is a downwardly depending switch cover 160 through which two rectangular openings 162 and 164 are provided. The switching function 20 is mounted upon a separate circuit board 166 which is seen to carry two push actuated switches as earlier described at 22 and 24 and identified by the same numeration in the instant figure. Located over the switches 22 and 24 is a flexible polymeric cover 168 formed of a flexible polymeric material such as Santoprene, a thermoplastic elastomer marketed by General Polymers of Charlotte, N.C. Circuit board 166 is supported between two slots formed in the interior of side components 56 and 58, one of these slots is seen at 170. The LCD 18 is mounted upon a circuit board 172 supported in turn, from interactive components 56 and 58. A bus-type wiring harness electrically associates the switching function 20, LCS 18, load cell assembly 102, the battery within compartment 74 and the circuitry carried by circuit board 76.
A sectional view of the instrument 10 is provided at
In
Turning to
Load cells 118 and 120 are represented with that numeration in
Each of the instruments 10 is calibrated using nineteen combinations of six standard weights. A best fit is determined and the instrument is called upon to have a root mean square error (RMS) of 0.1 pounds or less to pass calibration requirements. Once the calibration constants has been determined, the system is loaded with two redundant copies of the calibration constants. The zero point of the load cell is monitored at all times during the use of the instrument 10. If a drift is found, then a warning is shown at the LCD display 18. If any lead wire to the load cell becomes disconnected, then the built-in monitoring detects this occurrence, shows an error message, and disables further use of instrument 10 until the power is reset. These features insure that the force reading shown is accurate and true. Absolute values of the outputs of load cells 118 and 120 are summed to provide a force output signal. In general, the load measurement accuracy of instrument 10 is better than 0.1 pound or 0.1% of applied force whichever is greater.
In the discourse to follow, the sequences of the program protocol carried out by instrument 10 are represented in flow chart fashion. In general, these flow charts commence with a configuration sequence if desired and then look to two diagnostic protocols followed by two therapeutic protocols.
Turning to
With the publication of the screen as represented at block 246, then as represented at line 252 and block 254 the practitioner or user is called upon to determine whether to enter a configuration sequence or to progress to a diagnostic grip test. To enter the latter diagnostic grip test sequence, as represented at line 256 and block 258 by pressing switch 24 display 18 will prompt the user to press the select switch 24 to commence a diagnostic grip test sequence. Where the select switch 24 is actuated, then the program enters the diagnostic grip test sequence as represented at line 260 and node A.
Where a determination on the part of the practitioner or user is made to enter a configuration sequence, then as represented at line 262 and block 264 the configuration sequence is entered by actuating switch 22. As represented at line 266 and block 268 the initial configuration looks to units. Recall from block 246 that the instrument 10 defaults to a units evaluated in pounds. As represented at line 270 and block 272 by actuating select switch 24 the units parameter can be converted to kilograms instead of pounds. The program then continues upon depressing or actuating menu switch 22 as represented at either lines 274 or 276 leading to block 278. As represented at block 278, the user then is given the opportunity to delete the audible tone. In this regard, by actuating select switch 24, as represented at line 280 and block 282, the tone is deleted, display 18 showing the term “tone” in connection with the letter N.
The configuration sequence then continues as represented at either lines 283 or 284 with the actuation of menu switch 22. This actuation of switch 22 provides for the establishing of a rapid exchange diagnostic test cycle time change. As set forth at block 286 the default cycle time is 1.5 seconds. However, by actuation of select switch 24, as represented at line 288 and block 290 the operator may change the cycle time to 2.5 seconds. The program then continues by actuating the menu switch 22 as represented at either of lines 292 or 294. These lines lead to the configuration alteration represented at block 296. Recall from block 246 that the default number of exchanges for the rapid exchange diagnostic procedure is 10.
However, as represented at line 298 and block 300 the operator may change the number of exchanges from 10 to 20 by actuation of select switch 24. The program then returns to line 244 by actuation of the menu switch 22 as represented at lines 302 and 304. As described in connection with block 258, line 260 and node A, the operator may elect to proceed with a diagnostic grip test.
Referring to
Returning to block 316, the maximum strength grip test can be carried out with 10 maximum squeezing force trials. At the conclusion of a given number of such trials, the practitioner actuates select switch 24, whereupon computations are carried out. Accordingly, as represented at line 320 and block 322 the user is prompted with the message “squeeze hard!!!” at the readout 18. The program will elect the highest force applied during such squeezing activity, whereupon the user releases the grip force as represented at line 324 and block 326. Then instrument 10 will publish the maximum force applied by the user as represented at line 328 and block 330, a first maximum grip evaluation being shown as an example as 64.4 pounds. Block 330 also indicates that the user is prompted to either actuate the select switch 24 to accept the published maximum squeeze evaluation as set forth at block 330 or to squeeze the grip 14 again. Such squeezing again will provide a substitute maximum grip force evaluation. Then, as represented at line 332 and block 334 the query is posed as to whether the select switch 24 has been actuated. In the event that it has not, then the program loops as represented at line 336 extending to line 320, whereupon a maximum grip effort again is undertaken. Where the operator elects the maximum first trial grip force evaluation, then as represented at line 338 and block 340, the program will compute an average of force values, standard deviation and coefficient variation, albeit it for one trial at this junction in the procedure.
The program then continues as represented at line 342 and block 344 to display computed values which, as noted above, for the first trial are irrelevant. However, as the number of trials increases, those computed values gain significance. Next, as represented at line 346 and block 348 the program commences to carry out a next maximum grip test by providing a prompt at readout 18 which advises the user to “squeeze hard!!!” and indicates that this is a second trial as represented by the terms: “MAX 2”. Following a squeezing of the grip region 14, as represented at line 350 and block 352 the user releases the grip force and, as represented at line 354 and block 356 the maximum force asserted by the user is published, for example, showing 60 pounds for a “MAX 2” trial. This prompt further advises the user to actuate select switch 24 to elect the published grip force value or to squeeze again to carry out a next trial. The program then continues as represented at line 360 and block 362 to determine whether or not select switch 24 had been actuated. In the event that it had not been actuated then the program loops as represented at lines 364 and 346 whereupon the user again may carry out the second maximum grip trial. Where switch 24 has been actuated, then as represented at line 366 and block 368, the program carries out a computation of the average of the maximum forces asserted and computes standard deviation and coefficient of variation which are submitted to memory. The program then continues as represented at line 370 and block 372 whereupon the values computed in connection with block 368 are published at display 18. The above maximum grip test trials may be reiterated for 10 trials. Accordingly, as represented at line 374 and block 376 the maximum test trials are reiterated for a total of N tests (10 maximum) and the computed values of average force, standard deviation and coefficient of variation are both submitted to memory and published at display 18. As represented at line 378 and block 380 the user may restart this max test sequence following the Nth trial by actuating select switch 24, whereupon the program returns as represented at line 382 to 310 (
Returning to
Looking back to the query posed at block 334, where the menu switch 22 is actuated as opposed to electing a maximum grip value, then as represented at line 410 and block 412 the program will reconfigure for restarting the grip test mode. Once at this point in the program as represented at block 412, by again actuating select switch 24, the program reverts as represented at line 414 to line 320 to carry out another maximum grip trial. On the other hand, where menu switch 22 is actuated, as represented at line 416 and block 418 an indication will be given to the operator that to elect previous menu, select switch 24 is to be actuated. As represented at line 419, the program then reverts to node C. Node C again appears in
Looking again to
The diagnostic performance mode of the instrument 10 also provides for the carrying out of a rapid exchange (RE) test. With the rapid exchange test, the user may grip instrument 10 in the manner shown in
As represented at line 458 and block 460 the user will have squeezed the grip region 14 and the maximum hand force value evolved will be submitted to memory. Then as represented at line 462 and block 464 a determination is made as to whether the menu switch 22 has been actuated. In the event that it has not, as represented at line 466 and block 468 the program determines whether the Nth, i.e., 10th or 20th trial has been completed. In the event that it has not, then as represented at line 470 and block 472 the rapid exchange test has not been completed and an audible tone cue (time hack) is provided indicating that the instrument should be switched to the opposite hand. A short dwell occurs as represented at line 474 and block 476 wherein the instrument determines whether or not a squeeze force has been asserted. In the event that it has not, then the program loops as represented at line 478. Where the user has imparted a squeezing force to the instrument, the program continues or loops as represented at line 480 extending to line 458 leading to a next trial in an alternate hand.
Returning to block 464 where menu switch 22 is actuated in the course of carrying out rapid exchange trials, an affirmative determination will be made with respect to the query posed at that block. Accordingly, as represented at line 482 and block 484 the user is prompted to restart the rapid exchange test by actuating select switch 24. Where select switch 24 is actuated, then as represented at line 486 the program reverts to line 444 and block 446. On the other hand, where menu switch 22 is actuated, then as represented at line 488 and block 490 the user is prompted to revert to the previous menu by actuating select switch 24. Where select switch 24 is so actuated, then the program reverts to node C as represented at line 492. Note, additionally, that if menu switch 22 is actuated in conjunction with the prompt provided at block 442, then as represented at line 494 the program reverts to line 488. Returning to block 490, where menu switch 22 is actuated then as represented at line 496 and block 498 the program computes and displays the overall average of the maximum trial values, standard deviation and coefficient of variation for the N trials. That data is submitted to memory. Should menu switch 22 be actuated at this juncture, then as represented at lines 500 and 482, the program returns to block 484. Where the select switch 24 is actuated, however, as represented at line 502 and block 504 the maximum force value for trial N and the average SE and CD for all trials is displayed. On the other hand, where the menu switch 22 is actuated, then as represented at lines 506 and 482, the program reverts to block 484.
Where the select switch 24 is actuated repetitively, then as represented at line 508 and block 510 the succession of trials 1 through N is displayed. Additionally, the unchanging average for all those trials is displayed for convenience. Further, a query is posed as to whether the Nth trial has been displayed. Where it has not, then the display program loops as represented at line 512 extending to line 502. On the other hand, where the Nth trial has been displayed, then as represented at line 514, the program loops to line 502 to repeat the succession of displays.
It may be recalled that in conjunction with block 398 in
Following the target load computation, as represented at line 572 and block 573 the program displays the newly computed target force value at readout 18 along with the default values for number of repetitions (which defaults at 4), and the nominated hold on target interval and the rest interval (Table 1). As a prompt, the readout “4 REP” blinks to indicate that adjustment is available to the user. The program then continues as represented at line 574 which reappears in
Turning momentarily to
Returning to
Looking momentarily to
Returning to
Node G reappears in conjunction with line 708 (
Referring to
The number of steps elected adjusts the percentage of maximum grip force factor in accordance with a preordained schedule. That schedule is provided in Table 2 below. For example, if only one step is elected, that target grip factor will be 20%. On the other hand if five steps are elected, the first trial will be at 100% of maximum grip force. The second step will be at 80% of maximum grip force and so forth. On the other hand, if four steps are elected, the initial trial will be in conjunction with an 80% maximum grip force factor; the second step will be at 60% and so forth as set forth in Table 2. For each of these percentages as set forth in Table 2, the corresponding hold on target or effort interval and rest intervals will follow the values given above in Table 1.
The step value is elected by actuation of select switch 24 and the program continues as represented at line 758 and block 760. Block 760 replicates a display at readout 18 which prompts the user by indicating that the maximum elected gripping force selected was 90 pounds and that A steps were selected and a further prompt is provided showing blinking or intermittent display of “4 REPS”. Then, as represented at line 762 and block 764 the operator may adjust the number of repetitions of the program to a value within a preordained number of 1 through 10 by actuating menu switch 22. The elected number of repetitions then is selected by actuation of switch 24 and, as represented at line 766 and block 768 the system displays the now selected parameters of a maximum grip force, for example, 90 pounds, an election of A steps in the regimen and an election of “B” repetitions. Next, as represented at line 770 and block 772 the stepped exercise therapy is entered. Upon entry into this stepped exercise trial mode, target values are computed based upon the number of steps elected and the hold on target and rest intervals will be acquired, such data with respect to target factors being set forth in Table 2 and the latter hold on target and rest intervals being set forth in Table 1. This function is represented in block 776. Line 778 reappears in
Returning to block 780, where switch 24 has been actuated, then as represented at line 798 and block 800 the user is prompted to hold the grip force at the computed target level for 100%. Additionally, the prompt term “SQUEEZE” is provided within the readout 18. Next, as represented at line 802 and block 804 a determination is made as to whether the grip force exerted by the user is within 10% of the computed target value. Where it is not, then the system dwells as represented at loop line 806 and the display represented at block 800 continues. Where the asserted grip force is within 10% of the target load, then as represented at line 808 and block 810 the mandated hold on target interval timeout set forth in Table 1 commences and, as represented at line 812 and block 814 a dynamic comparison value is derived for dynamic bar graph cueing. Next, as represented at line 814 and block 816 a computation then is made as to whether the instantaneous grip force is at or above 125% of the target value. Where that is the case, then as represented at line 820 and block 822 an audible warning cue is sounded. The program then continues as represented at lines 824 and 826 when the excessive force has been lessened. Line 826 is directed to block 828 which provides for carrying out a computation of a score value as a percentage of target for a sequence of time increments. Computation of this score has been discussed in connection with
Line 830 reappears in
Following the generation of this audible cue, as represented at line 870 and block 872 the program reiterates the trial sequence following the mandates of Tables 1 and 2 and the elected parameters. As represented at line 874 and block 876, a query then is made as to whether the repetitions and associated efforts are complete. This value is the product of the elected number of steps A multiplied by the elected number of repetitions, B. Where that number of reiterations has not occurred, then the program continues as represented by look line 878 extending to line 870. Where the number of repetitions is completed, then as represented at line 880 and block 882 a final score is computed and submitted to memory with calendar and force data. Next, as represented at line 884 and block 886 the program selects a message to the user which will be based upon the final score. For example, the user may be advised to consult a therapist or the program directions in the event of the low score and is congratulated in the event of a good score. As represented at line 888 and block 890 those messages are selected. Where the user actuates select switch 24, the program continues as represented at line 892 and node H.
Turning again to
The user has the option of powering down instrument 10 by pressing select switch 24 for an interval of at least 2 seconds. This power off sequence is represented in the flow chart of
The protocol based isometric exercise approach of the invention has applicability to a broad range of muscle groups of the user. By employing the protocol which, inter alia, involves the evaluation of maximum muscle group strength as a precondition to then applying a factor related protocol, one of those factors may apply to the measured maximum strength value. The remaining factors which involve, for example, variations of target loads, hold times, rest intervals and exercise regimen planning in terms of calendar days achieves a safe and effective utilization of isometric activities. The exercisable anatomical features to be strengthened are generally identifiable as muscle groups of the human anatomy which may include but are not limited: jaw muscles, neck muscles, shoulder muscles, upper arm muscles, lower arm muscles, hand muscles, finger muscles, diaphragm muscles, abdominal muscles, lower back muscles, upper leg muscles, lower leg muscles, ankle muscles, foot muscles, and toe muscles.
Looking to
Through use of the invention, cardiac function and a variety of physiologic effects are produced, including effects on the endothelium and the release of biological active signaling molecules, including nitric oxide.
The following studies demonstrate the measureable biochemical and biophysical effect of utilization of the system, method, and apparatus of the invention.
Use of Isometric Exercise to Treat Hypertension
Among many other factors, both hypertension and arterial distensibility are independent risk factors for cardiovascular disease. The research of Wiley et al. (1992) and Taylor et al. (2003) demonstrated that isometric training is effective for reducing resting blood pressure (RBP). NO is a potent vasodilator, and crucial component of the regulation of vascular tension (See
As NO is a rapidly diffusible gas, release of NO in the blood vessels of the arms or other muscle groups, in response to isometric training, is expected to have both a local and systemic effect on vasodilation, arterial distensibility and resting blood pressure. Thus an increase of arterial distensibility in response to isometric exercise may contribute to reduction in RBP and increased NO bioavailability. A wide variety of muscle groups such as from exercisable regions of the musculature of the user including jaw muscles, neck muscles, shoulder muscles, upper arm muscles, lower arm muscles, hand muscles, finger muscles, diaphragm muscles, abdominal muscles, lower back muscles, upper leg muscles, lower leg muscles, ankle muscles, foot muscles, and toe muscles may provide a therapeutic benefit by utilization of the isometric exercise protocols of the invention.
To demonstrate the systemic effect of practicing the system and method of the invention, the impact of isometric arm and leg exercise on RBP and central and peripheral arterial distensibility was tested in patients being medicated for hypertension. Resting blood pressure was measured by brachial oscillometry, and arterial distensibility, as measured by Doppler ultrasound and applanation tonometry in the carotid, brachial and femoral arteries. Study participants were directed to perform isometric handgrip (IHG) exercise (n=10), or isometric leg press (ILP) exercise (n=6) according to the method of the invention three times per week for eight weeks. Exercise intensity was maintained at 30% of maximal voluntary contraction.
Following eight weeks of IHG exercise, systolic blood pressure decreased significantly (from 140.2 mmHg+/−3.82 to 132.3 mmHg+/−3.97), while no decrease was observed after isometric leg press exercise. Diastolic blood pressure did not change after either IHG or ILP exercise. Measurement of carotid arterial distensibility showed a significant improvement following IHG exercise (from 0.1105 mmHg−/−1.times.10.sup.-2 0.0093 to 0.1669 mmHg+/−1.times.10.sup.-2 0.0221), while no such changes occurred in the ILP exercise group. Peripheral arterial distensibility did not change following either IHG or ILP exercise. These studies demonstrate that the isometric handgrip exercise according to the invention improves resting systolic blood pressure and carotid arterial distensibility. As arterial tension is under the direct control of the NO/LDL-cholesterol signaling system, the system and method of the invention allows modulation of NO and indirectly of the LDL-cholesterol components.
As described previously, hypertension is associated with endothelial dysfunction, reduced NO bioavailability, and the development of coronary artery disease among other effects on the body of the patient. The isometric hand grip exercise protocol of the invention further reduces blood pressure even in patients already medicated for hypertension. In order to demonstrate the mechanisms of IHG affect on hypertension, endothelial function was studied in patients practicing the system and method of the invention. Study participants (n=8, 62+/−3.5 years) performed 4 sets of 2-minute isometric contractions at 30% of their maximal voluntary contraction. Ulnar reactivity was assessed in alternate hands, 3×/week for 8 weeks. Resting blood pressure was measured using automated brachial oscillometry. Vascular reactivity was measured in both arms using ultrasound imaging to determine brachial artery flow-mediated dilation (FMD). Following utilization of the IHG protocol of the invention, systolic blood pressure decreased (137 mm Hg+/−5.3 to 121.7 mm Hg=/−4.8 mmHg, p=0.03). Relative FMD increased (1.6%+/−0.3 to 4.5%+/−0.5 and normalized to average shear rate, 0.007%+/−0.001 to 0.02+/−0.004%/s−1). Reactive hyperemic flow decreased (peak, 344.3+/−36.5 to 258.2+/−27.2 ml/min and average, 301.6+/−33.1 to 239.0+/−28.4 ml/min). Average resting blood vessel diameter and resting flow rates remained unchanged.
As systemic shear stress is known to induce the activity of NO as a vasodilator, the IHG training apparently causes the release of NO, as shown by an increase in flow mediated arterial dilation. The IHG exercise protocol produced a reduced reactive hyperemic flow, accompanied by improvements in normalized FMD, and a heightened vasoreactive sensitivity to the reactive hyperemic stimulus. The IHG protocol by providing an improved cardiovascular function, demonstrates a modification of the wall shear stress setpoint for the activation of eNOS to produce biologically active levels of NO.
The statin class of drugs used in the treatment of hypercholesterolemia surprisingly has a pleiotropic effect on a variety of other systems of the body, including on the bioavailability of NO. Thus, by down-modulating cholesterol biosynthesis, statin drugs affect systems that are controlled by NO dependent signaling systems. The method and apparatus of the invention, surprisingly, by stimulating changes in the structure of the vasculature, and by creating increased wall shear stress in the blood vessels experiencing the effects of the inventive protocol, also induces broad effects on signaling systems including those that regulate the bioavailability of NO and serum cholesterol and LDL-cholesterol levels.
The above-described studies demonstrate use of the system and apparatus described herein to dilate blood vessels (e.g., arteries, arterioles) by causing the increased secretion of NO by inducing shear stress on blood vessel walls, resulting in positive effects on reducing hypertension. Thus, the system and apparatus described herein is also beneficial in treating other afflictions which may have their cause rooted in problems with the circulatory system (or which may be treated via improvement to the circulatory system of an affected individual). As described below, such afflictions may include ED, type 2 diabetes, and obesity.
Use of Isometric Exercise to Treat Erectile Dysfunction in Males
As described above, the system and method of the present invention may be used to dilate blood vessels by causing the increased secretion of NO by inducing shear stress on blood vessel walls. As ED is known to often have a circulatory component to its cause, and as the NO pathway plays an important role in the process of penile erection, the system and apparatus described herein is also beneficial in treating ED.
Mechanism of Penile Erection
As is known, penile erection may be achieved via two different mechanisms. The first is the reflex erection, which is achieved by a direct touching of the penile shaft. The second is the psychogenic erection, which is achieved by erotic or emotional stimuli. In general, stimulation of the penile shaft by the nervous system leads to the secretion of nitric oxide (NO), which causes the relaxation of smooth muscles of corpora cavernosa (the main erectile tissue of penis). If viewed in cross section, the penis consists of three tube-like projections of spongy tissue, the corpus spongiosum, located ventrally and the paired corpi cavernosi located dorsally. In each of the latter is the deep artery of the penis which carries blood over the length of the penis into the open channels that make up the corpus cavernosum. The blood carried out of the corpi cavernosi empties into the dorsal vein of the penis which then returns the blood to the body. The level of rigidity of the penis is due to the relationship between arterial inflow and venous outflow in the penis. This means that the larger the diameter of the arteries, the more blood enters the corpus cavernosum and enlarges the penis.
In the process of penile erection, NO is released with sexual stimulation from nerve endings and endothelial cells in the corpus cavernosum of the penis. NO activates soluble guanylate cyclase, enhancing production of guanosine 3′,5′-cyclic monophosphate (cGMP), by converting guanosine triphosphate (GTP) into cGMP. cGMP causes the smooth muscle to relax, which causes an inflow of blood, which then leads to an erection. cGMP is then hydrolyzed back to the inactive GMP by phosphodiesterase type 5 (PDE5).
Impotence may develop due to lack of adequate penile blood supply. For example, restriction of blood flow can arise from impaired endothelial function. This may be due to causes associated with coronary artery disease. Other conditions, such as diabetes and/or obesity may contribute to ED.
Medications to Treat ED
As is known to those of ordinary skill in the art, various medications may be taken to treat ED. The most common of these medications are phosphodiesterase type 5 inhibitors (PDE-5 inhibitors). The PDE-5 inhibitors sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) are prescription drugs which are taken orally. They work by blocking the action of PDE5, which causes cGMP to degrade (cGMP being necessary to a successful erection, as described above, by causing smooth muscle to relax, thereby causing inflow of blood to the penis; if cGMP is degraded, there is less smooth muscle relaxation, less inflow of blood, and no or weak erection).
The levels of cGMP are therefore controlled by the activation of cyclic nucleotide cyclase and the breakdown by PDE5. It is the latter that sildenafil acts upon. Men who suffer from erectile dysfunction often produce too little amounts of NO. This means that the small amount of cGMP they produce is broken down at the same rate and therefore doesn't have the time to accumulate and cause a prolonged vasodilation effect. Sildenafil works by inhibiting the enzyme PDE-5 by occupying its active site. This means that cGMP is not hydrolyzed as fast and this allows the smooth muscle to relax.
Use of Isometric Exercise with Individuals Suffering from ED
In view of the discussion above, it is clear that the NO pathway has an important role in achieving and maintaining an erection. It is also clear that, currently, expensive medications are the main treatment prescribed to those suffering from ED. However, with the principles of the method, system, and apparatus of the present invention, one may treat ED, and achieve and maintain erection, without the use of such medications, but rather through the use of isometric exercise.
Thus, like the method of the present invention for lowering the resting systolic and diastolic blood pressures of patients (described above), another aspect of the present invention includes a method for treating ED via isometric exercise (to stimulate increase of NO, and thus arterial dilation). In one embodiment, this method may begin by determining the maximal isometric force which can be exerted by a patient with any given muscle (e.g., skeletal muscle or group of muscles). The determined maximal isometric force is recorded, and the patient is periodically permitted to intermittently engage in isometric contraction of the given muscle at a fractional level of the maximal force determined for a given contraction duration followed by a given resting duration. When using a apparatus, (such as one described above), a perceptible indicia correlative to the isometric force exerted by the given muscle may be displayed to the patient so that the patient can sustain the given fractional level of maximal force.
A representative procedure for a patient to follow includes the patient exerting a force with a selected muscle or muscle group to about 50%.+−.5% of the previously determined maximal isometric force (of that muscle or muscle group) and holding that 50% force for 45 seconds; resting for one minute; and then repeating multiple times. The particular muscle or muscle group may be selected based upon the treatment desired. For example, the method may include exerting a squeezing force with either hand equal to about 50%.+−.5% of the previously determined maximal isometric force and holding that 50% force for 45 seconds; resting for one minute; exerting a force with the other hand equal to 50% of the maximum for 45 seconds; resting one minute; exerting a force of 50% of maximum for 45 seconds again with the first hand; resting one minute; and exerting a force of 50% for 45 seconds again with the second hand. This completes the isometric exercise for that day. The same procedure may be followed by the patient multiple days (e.g., at least five days per week). It will be recognized by those of ordinary skill in the art that the use of “hand” for the muscle group is exemplary. It will also be recognized by those of ordinary skill in the art that the protocol may be adapted based on the patient, the muscle group, the affliction, or other factors.
Thus, the isometric component of exercise alone can be used to stimulate NO production to increase arterial diameter and treat ED (via subsequent increased blood flow into the penis), by following a simple, yet effective, regimen that includes exerting fractional isometric force by any given muscle (for present purposes, “muscle” includes any skeletal muscle or group of muscles) for a given duration followed by a given duration of resting. This sequence is repeated several times (say, from about 3 to 6 times) and the entire regimen is repeated several times per week (say, from about 3 to 7 times per week). Since the regimen takes only several minutes per day to complete, it is believed that patients will be better able to stay with the program and, thus, receive long term benefits in treating ED. Moreover, since the patient exerts only a fraction of the maximal force of the given muscle, the patient's blood pressure during the exercise protocol does not rise to unacceptably high values whereat the patient's health would be at risk.
Another aspect of the therapeutic method associated with the instrument of the invention resides in the limiting of user performance to carry out the regimen of trials. In this regard, the instrument is programmed to perform only within predetermined and mandated test limits. Each therapeutic regimen is based upon an initial evaluation of the maximum gripping force capability of the user. Under that limitation, target load factors, hold on target load intervals, intervening rest intervals and trial repetition numbers may be elected only from pre-established and mandated memory retained ranges. The program also nominates rest intervals and hold on target intervals in correspondence with user elected target force factors. Thus, valuable strength recovery and development may be achieved but only within safe limits.
Additionally, the instrument is employable as a therapeutic device. First a protocol is nominated by prescribing nominal parameters of the effort. Each isometric regimen is controlled initially by requiring that a maximum grip strength be established for each individual patient or user. Then, the practitioner may elect parameters of grip force and timing under mandated memory contained parameter limits. Accordingly, the user will be unable to carry out strength enhancement therapies which would otherwise constitute an excessive grip force regimen. For carrying out the noted diagnostic procedures as well as therapy activities, the grip widthwise extent is variable from 1⅞ inches to 2⅞ inches, such variation being adjustable in ½ inch increments. This is in keeping with standardized diagnostic practices. Further with respect to diagnostic procedures, the display or readout of the instrument can be adjusted with respect to the grip structuring such that only the practitioner or therapist may observe the data which is being developed during a diagnostic protocol.
More particular description of examples of protocols are shown in
Use of Isometric Exercise to Enhance Sexual Stimulation in Females
Apart from the use of isometric exercise to treat sexual dysfunction (e.g., erectile dysfunction) in males, another aspect of the present invention also contemplates use of isometric exercise to enhance sexual function in females, particularly by enhancing clitoral sensitivity.
To that end, as described above, it is known that sildenafil (and other medications; PDE5 inhibitors) are effective treatments for male ED. Recent studies, however, have also shown that sildenafil can improve uterine circulation and clitoral artery blood flow, and that this occurs due to the same NO pathway as in penile erection.
For example, Alatas E, Yagci A B., The effect of sildenafil citrate on uterine and clitoral arterial blood flow in postmenopausal women, MedGenMed. 2004 Oct. 13; 6(4):51, incorporated by reference herein in its entirety, determined the effect of sildenafil on uterine circulation and clitoral artery blood flow in postmenopausal women using color Doppler sonography. After sildenafil administration, the mean resistance and pulsatility indexes of uterine artery were significantly lower (0.73±0.08 vs 0.80±0.07, P<0.001 and 1.66±0.50 vs 2.08±0.52, P<0.001, respectively) in comparison to baseline values, and the mean peak systolic velocity of clitoral artery was significantly higher (17.9±8.6 cm/sec vs 12.9±5.8 cm/sec, P<0.001). Sildenafil did not cause any significant change in the mean resistance and pulsatility indexes of the clitoral artery (P=0.683 and P=0.714, respectively). Thus, it was determined that sildenafil improves the clitoral and uterine blood flow in healthy postmenopausal women without any erotic stimulus. As a result, the NO pathway may be a candidate target for drug therapy for female sexual dysfunction.
Further studies have revealed that the neurovascular mechanism of this clitoral stimulation is NO-dependent. In one such study [Ferrante, S. G., et al., The neurovascular mechanism of clitoral erection: nitric oxide and cGMP-stimulated activation of BKCa channels, The FASEB Journal. 2004; 18:1382-1391, incorporated by reference herein in its entirety], the investigators hypothesized that rat clitorises relax by a similar mechanism as seen in penile erection (i.e., via the NO pathway). Rat clitorises express components of the proposed pathway: neuronal and endothelial NO synthases, soluble guanylyl cyclase (sGC), type 5 phosphodiesterase (PDE-5), and BKCa channels. The NO donor diethylamine NONOate (DEANO), the PKG activator 8-pCPT-cGMP, and the PDE-5 inhibitor sildenafil, cause dose-dependent clitoral relaxation that is inhibited by antagonists of PKG (Rp-8-Br-cGMPS) or BKCa channels (iberiotoxin). Electrical field stimulation induces tetrodotoxin-sensitive NO release and relaxation that is inhibited by the Na+ channel blocker tetrodotoxin or sGC inhibitor 1H-(1,2,4)oxadiozolo(4,3-a)quinoxalin-1-one. Human BKCa channels, transferred to Chinese hamster ovary cells via an adenoviral vector, and endogenous rat clitoral smooth muscle K+ current are activated by this PKG-dependent mechanism. Laser confocal microscopy reveals protein expression of BKCa channels on clitoral smooth muscle cells; these cells exhibit BKCa channel activity that is activated by both DEANO and sildenafil. Thus, the investigators concluded that neurovascular derived NO causes clitoral relaxation via a PKG-dependent activation of BKCa channels.
Further, as described previously, various PDE-5 inhibitors have been developed for human use (including sildenafil, vardenafil, and tadalafil) and they inhibit PDE-5 in cultured clitoral corpus cavernosal smooth muscle cells, relax the corpus cavernosum of the rabbit clitoris, and increase blood flow to the genitalia of the female dog. Thus, the present inventors conclude that use of such treatments for female mammals would be indicated across species, and thus would include humans (i.e., medications such as sildenafil would be useful for female sexual dysfunction in humans).
Berman J R, et al., Effect of sildenafil on subjective and physiologic parameters of the female sexual response in women with sexual arousal disorder, J Sex Marital Ther. 2001 October-December; 27(5):411-20, incorporated by reference herein in its entirety, supports this conclusion. Berman notes that sexual dysfunction is a complaint of 30-50% of American women and, aside from hormone replacement therapy, there currently are no FDA-approved medical treatments for female sexual complaints. The goal of the Berman study was to determine safety and efficacy of sildenafil for use in women with sexual arousal disorder (SAD). Following administration of sildenafil, poststimulation physiologic measurements improved significantly compared to baseline. Baseline subjective sexual function complaints, including low arousal, low desire, low sexual satisfaction, difficulty achieving orgasm, decreased vaginal lubrication, and dyspareunia [painful intercourse] also improved significantly following 6 weeks home use of sildenafil. Thus, Berman concluded that sildenafil significantly improves both subjective and physiologic parameters of the female sexual response. A follow-up study by Berman, [Berman J R, et al., Safety and efficacy of sildenafil citrate for the treatment of female sexual arousal disorder: a double-blind, placebo controlled study, J Urol. 2003 December; 170(6 Pt 1):2333-8, incorporated by reference herein in its entirety], also supported these conclusions.
For males, sildenafil may overcome the lack of penile erection, which disallowed intercourse. In females, this suggests that sildenafil may allow or enhance engorgement of the clitoris, which may enhance the pleasure of intercourse.
However, as with the drawbacks to drug therapies for male ED, similar issues exist with treatments for female sexual dysfunction, and so an aspect of the present invention provides a method, system, and apparatus for isometric exercise to improve clitoral artery blood flow for treatment of female sexual dysfunction, thereby obviating the need for drug-based treatment (such as with sildenafil or other drug compositions). Due to the studies showing potential use of sildenafil in females, the present invention also contemplates use of isometric exercise to allow or enhance engorgement of the clitoris, which may enhance the pleasure of intercourse. And so an aspect of the present invention provides a method, system, and apparatus for isometric exercise to improve clitoral artery blood flow for treatment of female sexual dysfunction.
Thus, like the method of the present invention for lowering the resting systolic and diastolic blood pressures of patients (described above), another aspect of the present invention includes a method for treating female sexual dysfunction via isometric exercise (to stimulate increase of NO, and thus arterial dilation). This method may begin with a determination of the maximal isometric force which can be exerted by a patient with any given muscle (e.g., skeletal muscle or group of muscles) of such patient. The determined maximal isometric force is recorded. The patient, then, is periodically permitted to intermittently engage in isometric contraction of the given muscle at a fractional level of the maximal force determined for a given contraction duration followed by a given resting duration. A perceptible indicia correlative to the isometric force exerted by the given muscle is displayed to the patient so that the patient can sustain the given fractional level of maximal force.
A representative procedure for a patient to follow includes the patient exerting a force with a selected muscle or muscle group to about 50%.+−.5% of the previously determined maximal isometric force (of that muscle or muscle group) and holding that 50% force for 45 seconds; resting for one minute; and then repeating multiple times. The particular muscle or muscle group may be selected based upon the treatment desired. For example, the method may include exerting a squeezing force with either hand equal to about 50%.+−.5% of the previously determined maximal isometric force and holding that 50% force for 45 seconds; resting for one minute; exerting a force with the other hand equal to 50% of the maximum for 45 seconds; resting one minute; exerting a force of 50% of maximum for 45 seconds again with the first hand; resting one minute; and exerting a force of 50% for 45 seconds again with the second hand. This completes the isometric exercise for that day. The same procedure may be followed by the patient multiple days (e.g., at least five days per week). It will be recognized by those of ordinary skill in the art that the use of “hand” for the muscle group is exemplary.
Thus, the isometric component of exercise alone can be used to stimulate NO production to increase arterial diameter and treat female sexual dysfunction, by following a simple, yet effective, regimen that includes exerting fractional isometric force by any given muscle (for present purposes, “muscle” includes any skeletal muscle or group of muscles) for a given duration followed by a given duration of resting. This sequence is repeated several times (say, from about 3 to 6 times) and the entire regimen is repeated several times per week (say, from about 3 to 7 times per week). Since the regimen takes only several minutes per day to complete, it is believed that patients will be better able to stay with the program and, thus, receive long term benefits in treating female sexual dysfunction. Moreover, since the patient exerts only a fraction of the maximal force of the given muscle, the patient's blood pressure during the exercise protocol does not rise to unacceptably high values whereat the patient's health would be at risk.
An important aspect of the therapeutic method associated with the instrument of the invention resides in the limiting of user performance to carry out the regimen of trials. In this regard, the instrument is programmed to perform only within predetermined and mandated test limits. Each therapeutic regimen is based upon an initial evaluation of the maximum gripping force capability of the user. Under that limitation, target load factors, hold on target load intervals, intervening rest intervals and trial repetition numbers may be elected only from pre-established and mandated memory retained ranges. The program also nominates rest intervals and hold on target intervals in correspondence with user elected target force factors. Thus, valuable strength recovery and development may be achieved but only within safe limits.
Additionally, the instrument is employable as a therapeutic device. First a protocol is nominated by prescribing nominal parameters of the effort. Each isometric regimen is controlled initially by requiring that a maximum grip strength be established for each individual patient or user. Then, the practitioner may elect parameters of grip force and timing under mandated memory contained parameter limits. Accordingly, the user will be unable to carry out strength enhancement therapies which would otherwise constitute an excessive grip force regimen. For carrying out the noted diagnostic procedures as well as therapy activities, the grip widthwise extent is variable from 1⅞ inches to 2⅞ inches, such variation being adjustable in ½ inch increments. This is in keeping with standardized diagnostic practices. Further with respect to diagnostic procedures, the display or readout of the instrument can be adjusted with respect to the grip structuring such that only the practitioner or therapist may observe the data which is being developed during a diagnostic protocol.
More particular description of examples of protocols are shown in
Use of Isometric Exercise to Treat Obesity
As described above, obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems. Obesity increases the likelihood of various diseases, such as heart disease and type 2 diabetes. And obesity is most commonly caused by a combination of excessive food energy intake, lack of physical activity, and genetic susceptibility.
Persons who are obese have increased, and often tremendous, amounts of fat stored in their bodies. The primary cells that make up these fat stores are white adipocytes (which make up the white adipose tissue). Apart from white adipose tissue, brown adipose tissue (BAT), or brown fat, is another type of fat. BAT is especially abundant in newborns and in hibernating mammals. Its primary function is to generate body heat in animals or newborns that do not shiver. In contrast to white adipocytes (fat cells), which contain a single lipid droplet, brown adipocytes contain numerous smaller droplets and a much higher number of mitochondria (these are involved in the metabolism of fat molecules, which release energy and heat, and get rid of the fat). Brown fat also contains more capillaries than white fat, since it has a greater need for oxygen than most tissues.
Recent studies using Positron Emission Tomography scanning of adult humans have shown that brown fat is present in adults in the upper chest and neck, though not to the extent it is present as a percentage of fat in newborns. These remaining deposits become more metabolically active with cold exposure, and less metabolically active if an adrenergic beta blocker is given before the scan. This could suggest a new method of weight loss, since brown fat takes calories from normal fat and burns it.
And indeed, more recently, it has been determined that by activating brown fat, one can burn white fat. For example, Cederberg A, et al., FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance, Cell. 2001 Sep. 7; 106(5):563-73 (incorporated by reference herein in its entirety), identified the human winged helix/forkhead transcription factor gene FOXC2 as a key regulator of adipocyte metabolism. Increased FOXC2 expression, in adipocytes, has a pleiotropic effect on gene expression, which leads to a lean and insulin sensitive phenotype. FOXC2 affects adipocyte metabolism by increasing the sensitivity of the beta-adrenergic-cAMP-protein kinase A (PKA) signaling pathway through alteration of adipocyte PKA holoenzyme composition.
Further, Boström, P., et al., A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis, Nature, Volume 481, pp. 463-468, Jan. 26, 2012, incorporated by reference herein in its entirety, demonstrated mechanisms by which exercise can improve metabolic status in obesity and type 2 diabetes.
As noted by Boström et al., exercise increases whole body energy expenditure beyond the calories used in the actual work performed. Because transgenic mice expressing PGC1-α selectively in muscle showed a remarkable resistance to age-related obesity and diabetes, Boström et al. sought factors secreted from muscle under the control of this co-activator that might increase whole body energy expenditure, and ultimately described a new polypeptide hormone, irisin (a cleaved and secreted portion of FNDC5), which is regulated by PGC1-α, secreted from muscle into blood, and activates thermogenic function in adipose tissues. Irisin has powerful effects on the browning of certain white adipose tissues, both in culture and in vivo. Nanomolar levels of this protein increase UCP1 in cultures of primary white fat cells by 50 fold or more, resulting in increased respiration. Further, viral delivery of irisin that causes only a moderate increase (˜3 fold) in circulating levels stimulates a 10-20 fold increase in UCP1, increased energy expenditure and an improvement in the glucose tolerance of mice fed a high fat diet. As this is in the range of increases seen with exercise in mouse and man, it is likely that irisin is responsible for at least some of the beneficial effects of exercise on the browning of adipose tissues and increases in energy expenditure.
Further, irisin is highly conserved in all mammalian species that have been sequenced. Mouse and human irisin are 100% identical, compared to 85% identity for insulin, 90% identity for glucagon, and 83% identity for leptin. This implies a highly conserved function that is likely to be mediated by a cell surface receptor.
On the basis of the gene structure of FNDC5, Boström et al. considered that FNDC5 might be a secreted protein. They observed that the signal peptide is removed, and the mature protein is further proteolytically cleaved and glycosylated, to release the 112-amino-acid polypeptide irisin. The cleavage and secretion of irisin is similar to the release/shedding of other transmembrane polypeptide hormones and hormone-like molecules such as epidermal growth factor (EGF) and transforming growth factor-α (TGF-α).
Thus, irisin would seem to have therapeutic potential. Exogenously administered irisin induces the browning of subcutaneous fat and thermogenesis, and it presumably could be prepared and delivered as an injectable polypeptide. Increased formation of brown or beige/brite fat has been shown to have anti-obesity, antidiabetic effects in multiple murine models, and adult humans have significant deposits of UCP1-positive brown fat. Data presented by Boström et al. show that even relatively short treatments of obese mice with irisin improves glucose homeostasis and causes a small weight loss. Whether longer treatments with irisin and/or higher doses would cause more weight loss remains to be determined. The worldwide, explosive increase in obesity and diabetes renders attractive the therapeutic potential of irisin in these and related disorders.
However, a treatment for obesity that includes injections of irisin presents drawbacks (e.g., medical supervision for injection—which involves time and travel; cost; etc.). Thus, like the method of the present invention for lowering the resting systolic and diastolic blood pressures of patients (described above), another aspect of the present invention includes a method for treating obesity via isometric exercise (to stimulate production and secretion of irisin). This method may begin with a determination of the maximal isometric force which can be exerted by a patient with any given muscle (e.g., skeletal muscle or group of muscles) of such patient. The determined maximal isometric force is recorded. The patient, then, is periodically permitted to intermittently engage in isometric contraction of the given muscle at a fractional level of the maximal force determined for a given contraction duration followed by a given resting duration. A perceptible indicia correlative to the isometric force exerted by the given muscle is displayed to the patient so that the patient can sustain the given fractional level of maximal force.
A representative procedure for a patient to follow includes the patient exerting a force with a selected muscle or muscle group to about 50%.+−.5% of the previously determined maximal isometric force (of that muscle or muscle group) and holding that 50% force for 45 seconds; resting for one minute; and then repeating multiple times. The particular muscle or muscle group may be selected based upon the treatment desired. For example, the method may include exerting a squeezing force with either hand equal to about 50%.+−.5% of the previously determined maximal isometric force and holding that 50% force for 45 seconds; resting for one minute; exerting a force with the other hand equal to 50% of the maximum for 45 seconds; resting one minute; exerting a force of 50% of maximum for 45 seconds again with the first hand; resting one minute; and exerting a force of 50% for 45 seconds again with the second hand. This completes the isometric exercise for that day. The same procedure may be followed by the patient multiple days (e.g., at least five days per week). It will be recognized by those of ordinary skill in the art that the use of “hand” for the muscle group is exemplary.
Thus, the isometric component of exercise alone can be used to stimulate production and secretion of irisin, to promote the browning of white fat, and treat obesity by following a simple, yet effective, regimen that includes exerting fractional isometric force by any given muscle (for present purposes, “muscle” includes any skeletal muscle or group of muscles) for a given duration followed by a given duration of resting. This sequence is repeated several times (say, from about 3 to 6 times) and the entire regimen is repeated several times per week (say, from about 3 to 7 times per week). Since the regimen takes only several minutes per day to complete, it is believed that patients will be better able to stay with the program and, thus, receive long term benefits in treating obesity. Moreover, since the patient exerts only a fraction of the maximal force of the given muscle, the patient's blood pressure during the exercise protocol does not rise to unacceptably high values whereat the patient's health would be at risk.
An important aspect of the therapeutic method associated with the instrument of the invention resides in the limiting of user performance to carry out the regimen of trials. In this regard, the instrument is programmed to perform only within predetermined and mandated test limits. Each therapeutic regimen is based upon an initial evaluation of the maximum gripping force capability of the user. Under that limitation, target load factors, hold on target load intervals, intervening rest intervals and trial repetition numbers may be elected only from pre-established and mandated memory retained ranges. The program also nominates rest intervals and hold on target intervals in correspondence with user elected target force factors. Thus, valuable strength recovery and development may be achieved but only within safe limits.
Additionally, the instrument is employable as a therapeutic device. First a protocol is nominated by prescribing nominal parameters of the effort. Each isometric regimen is controlled initially by requiring that a maximum grip strength be established for each individual patient or user. Then, the practitioner may elect parameters of grip force and timing under mandated memory contained parameter limits. Accordingly, the user will be unable to carry out strength enhancement therapies which would otherwise constitute an excessive grip force regimen. For carrying out the noted diagnostic procedures as well as therapy activities, the grip widthwise extent is variable from 1⅞ inches to 2⅞ inches, such variation being adjustable in ½ inch increments. This is in keeping with standardized diagnostic practices. Further with respect to diagnostic procedures, the display or readout of the instrument can be adjusted with respect to the grip structuring such that only the practitioner or therapist may observe the data which is being developed during a diagnostic protocol.
More particular description of examples of protocols are shown in
Use of Isometric Exercise to Treat Diabetes
As described above, type 2 diabetes is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Obesity is thought to be the primary cause of type 2 diabetes in people who are genetically predisposed to the disease. It is well known that there is an intimate link between type 2 diabetes and obesity. Above is disclosed the use of isometric exercise to combat obesity in individuals. As reduction of obesity is known to improve the diabetic condition by improving insulin sensitivity, another aspect of the present invention therefore contemplates the use of isometric exercise as therapy for type 2 diabetes.
In fact, recent studies have demonstrated an increase in the metabolic breakdown of glucose (and other carbohydrates) following isometric contraction of muscle, thereby reducing blood sugar levels. For example, in Katz A, Lee A D, G-1,6-P2 in human skeletal muscle after isometric contraction, Am J Physiol. 1988 August; 255(2 Pt 1):C145-8 (incorporated by reference herein in its entirety), the content of glucose 1,6-bisphosphate (G-1,6-P2), an in vitro activator of phosphofructokinase (a rate-limiting enzyme for glycolysis), and the glycolytic rate in skeletal muscle during isometric contraction were determined. In the study, subjects contracted the knee extensor muscles at two-thirds maximal voluntary force to fatigue, and biopsies from the quadriceps femoris muscle were obtained before and immediately after contraction. G-1,6-P2 increased in all subjects from a mean of 101+/−15 (SE) mumol/kg dry wt at rest to 128+/−24 at fatigue (P less than 0.05). Muscle glucose did not change significantly, whereas hexosemonophosphates were significantly increased after contraction. The glycogenolytic and glycolytic rate averaged 70.0+/−13.8 and 47.3+/−6.7 mmol·kg dry wt−1 min-1, respectively, and the glycolytic rate was positively correlated with the accumulation rates of fructose 6-phosphate (F-6-P) (r=0.95, P less than 0.01) and G-6-P (r=0.96, P less than 0.01). Phosphocreatine and ATP decreased by 87 and 17%, respectively, whereas ADP increased by 31% after contraction. These data demonstrate that intense, short-term isometric contraction results in an elevation of the muscle content of G-1,6-P2.
In another study, it was shown that diabetics respond the same as non-diabetics to stressors from isometric contractions (see, Kelleher C, Ferriss J B, Ross H, O'Sullivan D J, The pressor response to exercise and stress in uncomplicated insulin-dependent diabetes, J Hum Hypertens. 1987 June; 1(1):59-64, incorporated by reference herein in its entirety).
In that study, Kelleher et al. investigated whether or not an increased pressor response to exercise (i.e., the rise in blood pressure during isometric contractions) or stress is a feature of the diabetic state per se or a feature of its complications. Twelve insulin-dependent diabetic patients without clinical evidence of complications and with normal albumin excretion rates (less than 20 mg/min) were studied with 12 control subjects. Each underwent a study protocol of isometric handgrip exercise at 30% of maximum capacity for four minutes, a cold pressor test with immersion of one hand in ice-cold water for two minutes, and bicycle ergometry at a resistance of 105 watts per minute for six minutes. Both groups showed a similar and significant rise in systolic blood pressure and pulse rate in response to each stimulus. Diastolic pressure also rose significantly in response to handgrip exercise and to cold pressor stimulation. Mean plasma noradrenaline concentration rose in response to each stimulus but the changes reached conventional significance in both groups only in response to handgrip exercise. Pressor responses to exercise and stress, as tested in the study, were concluded to be normal in insulin-dependent diabetic patients without complications due to their disease. Thus, diabetics respond the same as non-diabetics to the stressors, which suggests a potential benefit for treating diabetecs with isometric exercise, since the rise in BP during the isometric contractions is the physiological signal that leads to the adaptive response of lower BP over time with repeated isometric training.
Further studies have likewise concluded that resistance training (i.e., isometric exercise) improves metabolic features and insulin sensitivity, and reduces abdominal fat in type 2 diabetic patients. For example, Bacchi E, et al., Metabolic Effects of Aerobic Training and Resistance Training in Type 2 Diabetic Subjects: A randomized controlled trial (the RAED2 study), Diabetes Care. 2012 Feb. 16, [Epub ahead of print], (incorporated by reference herein in its entirety), assessed differences between the effects of aerobic and resistance training on HbA(1c) (primary outcome) and several metabolic risk factors in subjects with type 2 diabetes, and to identify predictors of exercise-induced metabolic improvement. As is known, HbA(1c) is a form of hemoglobin that identifies average glucose in blood plasma over time, i.e. months.
In the study, type 2 diabetic patients (n=40) were randomly assigned to aerobic training or resistance training. Before and after 4 months of intervention, metabolic phenotypes (including HbA(1c), glucose clamp-measured insulin sensitivity, and oral glucose tolerance test-assessed β-cell function), body composition by dual-energy X-ray absorptiometry, visceral (VAT) and subcutaneous (SAT) adipose tissue by magnetic resonance imaging, cardiorespiratory fitness, and muscular strength were measured. After training, increase in peak oxygen consumption (VO(2peak)) was greater in the aerobic group (time-by-group interaction P=0.045), whereas increase in strength was greater in the resistance group (time-by-group interaction P<0.0001). HbA(1c) was similarly reduced in both groups (−0.40% [95% CI −0.61 to −0.18] vs. −0.35% [−0.59 to −0.10], respectively). Total and truncal fat, VAT, and SAT were also similarly reduced in both groups, whereas insulin sensitivity and lean limb mass were similarly increased. β-Cell function showed no significant changes. In multivariate analyses, improvement in HbA(1c) after training was independently predicted by baseline HbA(1c) and by changes in VO(2peak) and truncal fat. Thus, resistance training, similarly to aerobic training, improves metabolic features and insulin sensitivity and reduces abdominal fat in type 2 diabetic patients. Other studies have shown similar results (e.g., see Lambernd S., et al., Contractile activity of human skeletal muscle cells prevents insulin resistance by inhibiting pro-inflammatory signalling pathways, Diabetologia. 2012 Jan. 27, [Epub ahead of print], incorporated by reference herein in its entirety).
As described above, there are several metabolic links between diabetes and obesity. Put simply, if insulin resistance is high, glucose sugar is not metabolized and glucose and other sugars are readily converted to fats and stored. The studies cited herein use various methods of enhancing or blocking some of these interconnected metabolic pathways to illustrate the effects of exercise on skeletal muscle. Several of the recent studies included isometric contractions, voluntary or electrically induced, which makes it easier to connect or extrapolate from “rhythmic” contraction studies.
Other studies have elucidated the role and effect of certain factors on insulin sensitivity and signaling, even in aged animals. For example, Wenz T., et al., Increased muscle PGC-1 alpha expression protects from sarcopenia and metabolic disease during aging, Proc Natl Acad Sci USA. 2009 Dec. 1; 106(48):20405-10. Epub 2009 Nov. 16, incorporated by reference herein in its entirety, notes that aging is a major risk factor for metabolic disease and loss of skeletal muscle mass and strength, a condition known as sarcopenia. Both conditions present a major health burden to the elderly population. Wenz et al. analyzed the effect of mildly increased PGC-1alpha expression in skeletal muscle during aging, and found that transgenic MCK-PGC-1 alpha animals had preserved mitochondrial function, neuromuscular junctions, and muscle integrity during aging. Increased PGC-1alpha levels in skeletal muscle prevented muscle wasting by reducing apoptosis, autophagy, and proteasome degradation. The preservation of muscle integrity and function in MCK-PGC-1alpha animals resulted in significantly improved whole-body health; both the loss of bone mineral density and the increase of systemic chronic inflammation, observed during normal aging, were prevented. Importantly, MCK-PGC-1alpha animals also showed improved metabolic responses as evident by increased insulin sensitivity and insulin signaling in aged mice. These results of Wenz et al. highlight the importance of intact muscle function and metabolism for whole-body homeostasis and indicate that modulation of PGC-1alpha levels in skeletal muscle presents an avenue for the prevention and treatment of a group of age-related disorders.
Still other studies have examined the effect of exercise on insulin action. For example, Vind B F, et al., Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercise-training, Diabetologia. 2011 January; 54(1):157-67, Epub 2010 Oct. 13, (incorporated by reference herein in its entirety), notes that phosphorylation of TBC1 domain family, member 4 (TBC1D4) is, at present, the most distal insulin receptor signalling event linked to glucose transport, and examines insulin action on site-specific phosphorylation of TBC1D4 and the effect of exercise training on insulin action and signalling to TBC1D4 in skeletal muscle from type 2 diabetic patients.
In the study, during a 3 h euglycaemic-hyperinsulinaemic (80 mU min−1 m−2) clamp, Vind et al. obtained M. vastus lateralis biopsies from 13 obese type 2 diabetic and 13 obese, non-diabetic control individuals before and after 10 weeks of endurance exercise-training. Before training, reductions in insulin-stimulated R (d), together with impaired insulin-stimulated glycogen synthase fractional velocity, Akt Thr308 phosphorylation and phosphorylation of TBC1D4 at Ser318, Ser588 and Ser751 were observed in skeletal muscle from diabetic patients. Exercise-training normalized insulin-induced TBC1D4 phosphorylation in diabetic patients. This happened independently of increased TBC1D4 protein content, but exercise-training did not normalize Akt phosphorylation in diabetic patients. In both groups, training-induced improvements in insulin-stimulated R(d) (˜20%) were associated with increased muscle protein content of Akt, TBC1D4, α2-AMP-activated kinase (AMPK), glycogen synthase, hexokinase II and GLUT4 (20-75%).
Thus, it was concluded that impaired insulin-induced site-specific TBC1D4 phosphorylation may contribute to skeletal muscle insulin resistance in type 2 diabetes. And the mechanisms by which exercise-training improves insulin sensitivity in type 2 diabetes may involve augmented signalling of TBC1D4 and increased skeletal muscle content of key insulin signalling and effector proteins, e.g., Akt, TBC1D4, AMPK, glycogen synthase, GLUT4 and hexokinase II.
Finally, as noted, there is an intimate link between obesity and diabetes. Problems with obesity, and the aspect of the present invention for treating obesity with isometric exercise is discussed above. Part of that discussion focuses on the FOXC2 gene and a newly revealed hormone, irisin (see, Cederberg A, et al., FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance, Cell. 2001 Sep. 7; 106(5):563-73; and Boström P., et al., A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis, Nature. 2012 Jan. 11; 481(7382):463-8. doi: 10.1038/nature10777). Another aspect of the present invention contemplates many of the therapeutic benefits of this hormone (and its isometric exercise-induced secretion) also being used as a therapy for diabetes.
Thus, like the method of the present invention for lowering the resting systolic and diastolic blood pressures of patients (described above), another aspect of the present invention includes a method for treating diabetes via isometric exercise. This method may begin with a determination of the maximal isometric force which can be exerted by a patient with any given muscle (e.g., skeletal muscle or group of muscles) of such patient. The determined maximal isometric force is recorded. The patient, then, is periodically permitted to intermittently engage in isometric contraction of the given muscle at a fractional level of the maximal force determined for a given contraction duration followed by a given resting duration. A perceptible indicia correlative to the isometric force exerted by the given muscle is displayed to the patient so that the patient can sustain the given fractional level of maximal force.
A representative procedure for a patient to follow includes the patient exerting a force with a selected muscle or muscle group to about 50%.+−.5% of the previously determined maximal isometric force (of that muscle or muscle group) and holding that 50% force for 45 seconds; resting for one minute; and then repeating multiple times. The particular muscle or muscle group may be selected based upon the treatment desired. For example, the method may include exerting a squeezing force with either hand equal to about 50%.+−.5% of the previously determined maximal isometric force and holding that 50% force for 45 seconds; resting for one minute; exerting a force with the other hand equal to 50% of the maximum for 45 seconds; resting one minute; exerting a force of 50% of maximum for 45 seconds again with the first hand; resting one minute; and exerting a force of 50% for 45 seconds again with the second hand. This completes the isometric exercise for that day. The same procedure may be followed by the patient multiple days (e.g., at least five days per week). It will be recognized by those of ordinary skill in the art that the use of “hand” for the muscle group is exemplary.
Thus, the isometric component of exercise alone can be used to stimulate NO production to increase arterial diameter and treat diabetes, by following a simple, yet effective, regimen that includes exerting fractional isometric force by any given muscle (for present purposes, “muscle” includes any skeletal muscle or group of muscles) for a given duration followed by a given duration of resting. This sequence is repeated several times (say, from about 3 to 6 times) and the entire regimen is repeated several times per week (say, from about 3 to 7 times per week). Since the regimen takes only several minutes per day to complete, it is believed that patients will be better able to stay with the program and, thus, receive long term benefits in treating diabetes. Moreover, since the patient exerts only a fraction of the maximal force of the given muscle, the patient's blood pressure during the exercise protocol does not rise to unacceptably high values whereat the patient's health would be at risk.
An important aspect of the therapeutic method associated with the instrument of the invention resides in the limiting of user performance to carry out the regimen of trials. In this regard, the instrument is programmed to perform only within predetermined and mandated test limits. Each therapeutic regimen is based upon an initial evaluation of the maximum gripping force capability of the user. Under that limitation, target load factors, hold on target load intervals, intervening rest intervals and trial repetition numbers may be elected only from pre-established and mandated memory retained ranges. The program also nominates rest intervals and hold on target intervals in correspondence with user elected target force factors. Thus, valuable strength recovery and development may be achieved but only within safe limits.
Additionally, the instrument is employable as a therapeutic device. First a protocol is nominated by prescribing nominal parameters of the effort. Each isometric regimen is controlled initially by requiring that a maximum grip strength be established for each individual patient or user. Then, the practitioner may elect parameters of grip force and timing under mandated memory contained parameter limits. Accordingly, the user will be unable to carry out strength enhancement therapies which would otherwise constitute an excessive grip force regimen. For carrying out the noted diagnostic procedures as well as therapy activities, the grip widthwise extent is variable from 17/8 inches to 27/8 inches, such variation being adjustable in ½ inch increments. This is in keeping with standardized diagnostic practices. Further with respect to diagnostic procedures, the display or readout of the instrument can be adjusted with respect to the grip structuring such that only the practitioner or therapist may observe the data which is being developed during a diagnostic protocol.
More particular description of examples of protocols are shown in
While the various aspects of the present invention have been disclosed by reference to the details of various embodiments of the invention, it is to be understood that the disclosure is intended as an illustrative rather than in a limiting sense, as it is contemplated that modifications will readily occur to those skilled in the art, within the spirit of the invention and the scope of the appended claims.
This application claims the benefit of the filing date of U.S. Patent Application Ser. No. 61/724,008, entitled “Isometric System, Method and Apparatus for Isometric Exercise,” filed on Nov. 8, 2012, the disclosure of which is incorporated by reference herein in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 61724008 | Nov 2012 | US |
