Patent Grant
8855783
The present application is related to U.S. Provisional Application 61/532,660, filed Sep. 9, 2011, which is incorporated herein by reference.
Some applications of the present invention generally relate to medical apparatus. Specifically, some applications of the present invention relate to apparatus and methods for treating congestive heart failure, diastolic heart failure, hypertension, pulmonary hypertension, and/or other conditions.
Heart failure is a condition in which a problem with the structure or function of the heart impairs its ability to supply sufficient blood flow to meet the body's needs. The condition impairs quality of life and is a leading cause of hospitalizations and mortality in the western world. Treatment of heart failure is typically aimed at removal of precipitating causes, prevention of deterioration in cardiac function, and control of congestive state.
Hypertension, or chronic high blood pressure, is an extremely prevalent medical condition, which can lead to strokes, heart attacks, and heart failure. There are a variety of treatments that are available for treating hypertension, including lifestyle changes, and medication.
For some applications of the present invention, a subject suffering from congestive heart failure, diastolic heart failure, hypertension, and/or another disorder is identified. The subject is typically treated by implanting at least one electrode on the subject's vagus nerve at a vagal site and/or at an aortic site that is typically as described hereinbelow. Typically, a plurality of electrodes are implanted at the vagal site, and/or the aortic site. The subject is treated by driving a current into the electrode implantation site. The effects of driving the current into the implantation site typically include ventricular and aortic pressure reduction, an increase in aortic compliance, a decrease in sympathetic tone, a decrease in heart rate, and/or an increase in parasympathetic tone. These effects are typically advantageous in treating heart failure.
In some applications of the invention, an external device is used to detect one or more factors associated with the disorder of the subject. The external device transmits a signal, which is received by an implant. The implant is configured and positioned to stimulate an electrode implantation site of the subject, at least in part responsively to the received signal. Typically, the apparatus is configured to operate only when the external device is located in proximity to the subject. For example, in some applications of the invention, the external device is located in, near or under a bed and/or chair of the subject, such that detection of the factors by the external device, and/or detection of the signal by the implant, occur only when the subject is in/on the bed and/or chair.
In some applications of the invention, the implant functions by stimulating a portion of the aorta (i.e., an aortic site) of the subject that is between the bifurcation of the aorta with the left subclavian artery and the bifurcation of the aorta with the fifth intercostal artery. For example the aortic site may be (a) between the bifurcation of the aorta with the left subclavian artery and a location 4 cm downstream of the bifurcation, (b) between the bifurcation of the aorta with the left subclavian artery and the bifurcation of the aorta with the fourth intercostal artery, (c) between the bifurcation of the aorta with the left subclavian artery and the bifurcation of the aorta with the first intercostal artery, and/or (d) between the bifurcations of the aorta with the first and fifth intercostal arteries.
In some applications, the aortic site is adjacent to a portion of a vagus nerve of the subject that is between (a) a vagal bifurcation with a thoracic cardiac branch from a left recurrent laryngeal of the subject, and (b) thoracic vagal branching into the esophageal plexus of the subject. In some applications, the aortic site is adjacent to a portion of a vagus nerve of the subject that is between (a) an upper junction of a left thoracic vagal trunk with the left subclavian artery, and (b) a vagal bifurcation with a thoracic cardiac branch from a left recurrent laryngeal of the subject.
In some applications of the invention, the implant functions by stimulating a portion of the vagus nerve (i.e., a vagal site) of the subject that is between (a) a vagal bifurcation with a thoracic cardiac branch from a left recurrent laryngeal of the subject, and (b) thoracic vagal branching into the esophageal plexus of the subject. In some applications, the vagal site is between (a) an upper junction of a left thoracic vagal trunk with the left subclavian artery, and (b) a vagal bifurcation with a thoracic cardiac branch from a left recurrent laryngeal of the subject.
In some applications of the invention, the implant receives power wirelessly. In some applications, the implant receives power via electromagnetic induction. In some applications, the implant receives power via electromagnetic radiation.
There is therefore provided, in accordance with an application of the present invention, apparatus for treating a subject, the apparatus including:
an external device, configured for placement outside of the subject, the external device including:
an implant, including:
In an application, the detector is configured to detect a factor associated with a disorder of the subject.
In an application, the detector is configured to detect a factor associated with a physiological state of the subject.
In an application, the electrode is configured to be placed in contact with an aortic site that is adjacent to a portion of a vagus nerve of the subject that is between (a) a vagal bifurcation with a thoracic cardiac branch from a left recurrent laryngeal of the subject, and (b) thoracic vagal branching into the esophageal plexus of the subject.
In an application, the electrode is configured to be placed in contact with an aortic site that is adjacent to a portion of a vagus nerve of the subject that is between (a) an upper junction of a left thoracic vagal trunk with the left subclavian artery, and (b) a vagal bifurcation with a thoracic cardiac branch from a left recurrent laryngeal of the subject.
In an application, the driver unit is configured to reduce ventricular pressure of the subject.
In an application, the driver unit is configured to reduce aortic pressure of the subject.
In an application, the driver unit is configured to reduce sympathetic tone of the subject.
In an application, the driver unit is configured to increase parasympathetic tone of the subject.
In an application, the driver unit is configured to increase parasympathetic tone of the subject and reduce sympathetic tone of the subject.
In an application, the detector is configured to detect a breathing-related factor of the subject.
In an application, the external device is configured to detect reclining of the subject, and to generate the signal at least in part responsively to the reclining of the subject.
In an application, the external device is configured to detect sitting of the subject, and to generate the signal at least in part responsively to the detecting of the sitting of the subject.
In an application, the implant is configured to detect reclining of the subject, and the driver unit is configured to drive the effector element at least in part responsively to the reclining of the subject.
In an application, the detector is configured to detect an electrical factor of the subject.
In an application, the detector is configured to detect chest movement of the subject.
In an application, the detector is configured to detect arterial pulses of the subject.
In an application, the detector is configured to detect a body position of the subject.
In an application, the detector is configured to detect an oxygen saturation of the subject.
In an application, the detector is configured to detect a nasal airflow of the subject.
In an application, the control unit is configured to generate the signal as a radio frequency signal.
In an application, the control unit is configured to generate the signal as a magnetic signal.
In an application, the electrode is configured to be placed in contact with an aorta of the subject.
In an application, the electrode is configured to be placed in contact with an aortic site that is between (a) the bifurcation of the aorta with a left subclavian artery and (b) the bifurcation of the aorta with a fifth intercostal artery of the subject.
In an application, the electrode is configured to be placed in contact with an aortic site that is between (a) the bifurcation of the aorta with the left subclavian artery and (b) a bifurcation of the aorta with a fourth intercostal artery of the subject.
In an application, the electrode is configured to be placed in contact with an aortic site that is between (a) the bifurcation of the aorta with the left subclavian artery and (b) a bifurcation of the aorta with a first intercostal artery of the subject.
In an application, the electrode is configured to be placed in contact with an aortic site that is between (a) the bifurcation of the aorta with the fifth intercostal artery and (b) the bifurcation of the aorta with the fourth intercostal artery of the subject.
In an application, the driver unit is configured to reduce a ratio of a low frequency component to a high frequency component of heart rate variability of the subject.
In an application, the driver unit is configured to reduce a ratio of (1) a low frequency component of less than 0.05 Hz, to (2) a high frequency component of between 0.15 and 0.35 Hz, of heart rate variability of the subject.
In an application, the implant is configured to wirelessly receive power.
In an application, the implant is configured to receive the power from the signal.
In an application, the control unit is configured to generate a second signal, and the implant is configured to receive the power from the second signal.
In an application, the implant is configured to receive power via magnetic induction.
In an application, the external device is configured to transmit power via magnetic induction.
In an application, the implant is configured to receive power via electromagnetic radiation transmitted by the external device.
In an application, the implant includes a rectifying antenna configured to receive the power.
There is further provided, in accordance with an application of the present invention, apparatus for treating a subject, the apparatus including:
an external device, configured for placement outside of the subject, the external device including:
an implant, including:
In an application, the detector is configured to detect a factor associated with a disorder of the subject.
In an application, the detector is configured to detect a factor associated with a physiological state of the subject.
In an application, the electrode is configured to be placed in contact with a vagus nerve of the subject.
In an application, the electrode is configured to be placed in contact with a vagal site that is between (a) a vagal bifurcation with a thoracic cardiac branch from a left recurrent laryngeal of the subject, and (b) thoracic vagal branching into the esophageal plexus of the subject.
In an application, the electrode is configured to be placed in contact with a vagal site that is between (a) an upper junction of a left thoracic vagal trunk with the left subclavian artery, and (b) a vagal bifurcation with a thoracic cardiac branch from a left recurrent laryngeal of the subject.
There is further provided, in accordance with an application of the present invention, a method for treating a subject, the method including:
extracorporeally detecting a factor associated with a state of the subject;
automatically extracorporeally generating a signal, at least in part responsively to the detected factor;
intracorporeally detecting the signal; and
automatically stimulating an aortic site of the subject, at least in part responsively to the signal.
In an application, extracorporeally detecting the factor includes extracorporeally detecting a factor associated with a disorder of the subject.
In an application, extracorporeally detecting the factor includes extracorporeally detecting a factor associated with a physiological state of the subject.
In an application, extracorporeally detecting the factor includes extracorporeally detecting the factor while the subject is sleeping.
In an application, extracorporeally detecting the factor includes extracorporeally detecting a breathing-related factor of the subject.
In an application, extracorporeally detecting the factor includes extracorporeally detecting an electrical factor of the subject.
In an application, extracorporeally detecting the factor includes extracorporeally detecting a heart cycle of the subject.
In an application, stimulating the aortic site includes stimulating an aortic site that is adjacent to a portion of a vagus nerve of the subject that is between (a) a vagal bifurcation with a thoracic cardiac branch from a left recurrent laryngeal of the subject, and (b) thoracic vagal branching into the esophageal plexus of the subject.
In an application, stimulating the aortic site includes stimulating an aortic site that is adjacent to a portion of a vagus nerve of the subject that is between (a) an upper junction of a left thoracic vagal trunk with the left subclavian artery, and (b) a vagal bifurcation with a thoracic cardiac branch from a left recurrent laryngeal of the subject.
In an application, stimulating the electrode implantation site includes reducing ventricular pressure of the subject.
In an application, stimulating the electrode implantation site includes reducing aortic pressure of the subject.
In an application, stimulating the electrode implantation site includes reducing sympathetic tone of the subject.
In an application, stimulating the electrode implantation site includes increasing parasympathetic tone of the subject.
In an application, stimulating the electrode implantation site includes increasing parasympathetic tone of the subject and reducing sympathetic tone of the subject.
In an application, stimulating the electrode implantation site includes increasing aortic compliance of the subject.
In an application, intracorporeally detecting the signal includes wirelessly receiving power via the signal, using an implant, and automatically altering the blood flow includes powering the implant using the received power.
In an application, intracorporeally detecting the signal includes wirelessly receiving data via the signal, using an implant, and automatically altering the blood flow includes operating the implant responsively to the received data.
In an application,
intracorporeally detecting the signal includes wirelessly receiving power via the signal, using an implant, and automatically altering the blood flow includes powering the implant using the received power, and
intracorporeally detecting the signal includes wirelessly receiving data via the signal, using the implant, and automatically altering the blood flow includes operating the implant responsively to the received data.
In an application, generating the signal includes generating a radio frequency signal, and detecting the signal includes detecting the radio frequency signal.
In an application, generating the signal includes generating a magnetic signal, and detecting the signal includes detecting the magnetic signal.
In an application, stimulating the aortic site includes stimulating an aortic site that is between (a) the bifurcation of the aorta with a left subclavian artery and (b) the bifurcation of the aorta with a fifth intercostal artery of the subject.
In an application, stimulating the aortic site includes stimulating an aortic site that is between (a) the bifurcation of the aorta with the left subclavian artery and (b) a bifurcation of the aorta with a fourth intercostal artery of the subject.
In an application, stimulating the aortic site includes stimulating an aortic site that is between (a) the bifurcation of the aorta with the left subclavian artery and (b) a bifurcation of the aorta with a first intercostal artery of the subject.
In an application, stimulating the aortic site includes stimulating an aortic site that is between (a) the bifurcation of the aorta with the fifth intercostal artery and (b) the bifurcation of the aorta with the fourth intercostal artery of the subject.
In an application, stimulating the electrode implantation site includes reducing a ratio of a low frequency component to a high frequency component of heart rate variability of the subject.
In an application, stimulating the electrode implantation site includes reducing a ratio of (1) a low frequency component of less than 0.05 Hz, to (2) a high frequency component of between 0.15 and 0.35 Hz, of heart rate variability of the subject.
There is further provided, in accordance with an application of the present invention, a method for treating a subject, the method including:
extracorporeally detecting a factor associated with a state of the subject;
automatically extracorporeally generating a signal, at least in part responsively to the detected factor;
intracorporeally detecting the signal; and
automatically stimulating a vagal site of the subject, at least in part responsively to the signal.
In an application, stimulating the vagal site includes stimulating a portion of a vagus nerve of the subject.
In an application, stimulating the vagal site includes stimulating a vagal site that is between (a) a vagal bifurcation with a thoracic cardiac branch from a left recurrent laryngeal of the subject, and (b) thoracic vagal branching into the esophageal plexus of the subject.
In an application, stimulating the vagal site includes stimulating a vagal site of the subject that is between (a) an upper junction of a left thoracic vagal trunk with the left subclavian artery, and (b) a vagal bifurcation with a thoracic cardiac branch from a left recurrent laryngeal of the subject.
The present invention will be more fully understood from the following detailed description of embodiments thereof, taken together with the drawings, in which:
Reference is made to
External device 24, in accordance with some applications of the present invention, is placed in proximity to the subject, under the subject, under or inside the subject's pillow or mattress, or on another part of the bed (e.g., on a bedpost). Alternatively, the external device can be placed on, in, or under a chair of the subject. Alternatively, the external device can be placed anywhere near the subject, such that implant 40 receives signals 32 from the external device. For some applications of the invention, external device 24 is portable and/or wearable by the subject. External device 24 may be coupled to and/or disposed within an item of clothing (e.g., a hat; a belt) of the subject, or worn on a chest-band. The antennas 30 of external device 24 are typically configured to send signals 32 to the implant, as described hereinbelow.
External device 24 typically sends signals 32 to implant 40. At least in part responsively to signals 32, implant 40 provides electrical stimulation at the site of implantation. For some applications, external device 24 sends signals 32 to implant 40 for a pre-determined length of time or in a particular pattern, or both. For some applications, periods of no stimulation by implant 40 are provided. In addition, external device 24 may be configured to only provide signals 32 to implant 40 when subject 22 is reclining (e.g., when the subject is sleeping). For example, in some applications, a sensor (e.g., sensor 28) is positioned in, on or under a mattress, and configured to detect the weight of the subject, and control unit 26 is configured to only transmit signals 32 when the weight of the subject is detected. Alternatively or additionally, as described hereinbelow (e.g., with reference to
Typically, signals 32 comprise data, and implant 40 receives the data and responds to the data. In some applications of the invention, external device 24 wirelessly powers implant 40 via wireless power 132, as described hereinbelow. When external device 24 wirelessly powers implant 40, wireless power 132 may comprise signals 32 and, thereby, comprise the data to which implant 40 typically responds. For some applications of the invention, the data may comprise an on/off command. For some applications of the invention, and as described hereinbelow (e.g., with reference to FIGS. 2A and 3A-C), implant 40 may be configured to only function when wireless power 132 is being received. In these applications, signals 32 may comprise only wireless power 132. That is, when signals 32 (i.e., wireless power 132) are received by implant 40, the implant is commanded (i.e., enabled) to function, and when signals 32 (i.e., wireless power 132) are not received by the implant, the implant is commanded not to function (i.e., is disabled from operating).
One or more of the implants are typically implanted into the subject at the aortic site and/or at the vagal site of the subject. These one or more implants 40 may be configured to work in conjunction with other implants or independent of each other and/or external device 24. It is noted that the number of implants 40 in the illustration is by way of illustration and not limitation.
Closed-loop control (i.e., feedback control) is typically facilitated by continuous and/or repeated detection, by sensor 28, of the factors described hereinabove. In some applications of the invention, feedback is alternatively or additionally provided by subject 22 himself, or by other sensors such as additional feedback sensors (not shown). In addition, other sensors known in the art may be used to obtain feedback and to support feedback control of external device 24 and implant 40. Typically, sensing and responsive modulation of the electrical stimulation parameters is continuous and/or repeated over a duration of time (e.g., more than one hour, e.g., more than 4 hours, e.g., overnight). For severe conditions (e.g., bedridden subjects), sensing and responsive modulation of the electrical stimulation parameters may continue indefinitely.
Reference is made to
Reference is now made to
Control unit 26 drives antenna 30 to transmit one or more signals 32, which is received by implant 40 when within an appropriate range. For example, the apparatus may be configured such that implant 40 is typically able to use signals 32 only when the subject is close to external device (e.g., within 10 m, e.g., within 5 m, e.g., within 1 m, e.g., when the subject is in bed). Typically, control unit 26 drives such signal transmission at least in part responsively to the one or more parameters detected by sensor 28. Alternatively or additionally, control unit 26 may drive signal transmission for a pre-determined and/or configurable length of time, or in a particular pattern. For some applications of the invention, signals 32 provide power to implant 40, as described hereinbelow. External device 24 may further comprise one or more additional feedback sensors 44, which detect one or more feedback parameters that indicate the efficacy and/or efficiency of the treatment applied by the implant 40. Alternatively or additionally, the feedback parameters may be the same as the parameters detected by sensor 28, in which case, feedback control is provided without the requirement for feedback sensor 44. Alternatively or additionally, feedback may be provided by the subject himself.
In some applications of the invention, external device 24 may further comprise one or more induction coils 42. Induction coils 42 are configured to supply power, via electromagnetic induction, to implant 40, in conjunction with one or more corresponding induction coils in the implant (not shown). This power may be consumed immediately by implant 40 and/or may be used to charge a power supply, as described hereinbelow.
Reference is now made to
Reference is now made to
Reference is made to
Reference is now made to
As described with reference to
In some applications of the invention, implant 40 may receive power via electromagnetic radiation (e.g., radio waves and/or microwaves), such as wireless power 132. In such applications of the invention, power-receiver 130 comprises a rectifying antenna (rectenna) 136, which converts wireless power 132 into electrical energy. In some applications of the invention, wireless power 132 may be a dedicated charging signal, transmitted by external device 24. Alternatively or additionally, wireless power 132 may include signals 32, which drive the implant to drive a current into the implantation site such as to at least in part treat the subject's condition. In some applications of the invention, implant 40 either does not comprise antenna 46, or does not comprise power-receiver 30. Rather, signals 32 and wireless power 132 are both received via either antenna 46, or by power-receiver 130.
Electrical energy supplied by power-receiver 130 typically charges power supply 138, such that implant 40 may function in the absence of continuous wireless power. Alternatively or additionally, electrical energy supplied by power-receiver 130 may be consumed by implant 42 as it is supplied. In some applications of the invention, driver unit 66 drives element 50 only while wireless power 132 is being received by power-receiver 130.
Reference is now made to
Reference is now made to
Typically, the compliance of stent implant 340 varies along the length of the stent. For some applications, the compliance of the stent varies along the length of the stent in a manner that conforms with local stresses exerted on the stent by collagen fibers of the blood vessel. For some applications, the compliance of the stent varies along the length of the stent in a manner that facilitates placement of the stent in a curved blood vessel, the stent being configured to conform with the local shape of the blood vessel.
Typically, stent implant 340 includes a plurality of strut portions along the length of the implant, and the strut portions are coupled to each other at junctions, for example, junctions that include springs 338. Typically, the compliance of implant 340 at the junctions is greater than the compliance of the implant at the strut portions. For some applications, implant 340 is configured to be placed in a curved blood vessel. For some applications, the compliance of the implant at the junctions facilitates curvature of the implant that conforms with the curvature of the blood vessel. For example, the compliance of the implant at the junctions may facilitate curvature of the implant such that local longitudinal axes of respective strut portions of the implant are aligned with local longitudinal axes of a curved blood vessel.
For example, with reference to
Implant 340 is typically configured to be placed inside the blood vessel (e.g., the aorta) via an endovascular approach, either percutaneously or via a small incision to expose an artery, e.g., using a 12 Fr-20 Fr catheter (e.g., a 14 Fr-18 Fr catheter, such as a 16 Fr catheter). Typically, the arterial access point is through a femoral artery. Typically, upon being placed inside the blood vessel, the implant is partially deployed, such that (a) electrodes 219 contact the wall of the blood vessel at a given location within the blood vessel, and (b) a proximal portion of the implant is disposed inside the catheter, such that the implant may be retrieved into the catheter. The physiological response (e.g., change in heart rate, arterial pressure, and/or ventricular pressure) of the subject to electrical stimulation of the blood vessel at the current location of the electrodes within the blood vessel is determined. In response thereto, the implant is (a) fully deployed at the current location of the implant (b) retrieved into the catheter and redeployed at a different location within the blood vessel, or (c) retrieved into the catheter and removed from the subject's body (e.g., if the subject does not respond in a suitable manner to electrical stimulation of the blood vessel at the locations at which the implant is deployed).
Typically, the compliance of implant 340 is such that pulsation of the blood vessel is substantially maintained upon the implant being deployed inside the blood vessel. Further typically, the implant and components coupled thereto are shaped such as to substantially maintain blood flow through the blood vessel upon deployment of the implant inside the blood vessel.
For some applications, implant 340 is cut from a nitinol tube (or a tube made from a different material, such as stainless steel) having a wall thickness of more than 0.3 mm (e.g., more than 0.4 mm), and/or less than 0.7 mm (e.g., less than 0.6 mm). For some applications the length of the implant is more than 25 mm (e.g., more than 30 mm), and/or less than 50 mm (e.g., less than 40 mm). For some applications, the implant has an outer diameter of more than 10 mm (e.g., more than 15 mm), and/or less than 35 mm (e.g., less than 25 mm). Typically, the implant has a crimped (i.e., compressed) profile of less than 18 Fr (e.g., 12 Fr or less), and/or more than 8 Fr (e.g., 10 Fr or more).
For some applications, one or more portions of implant 340 function as antennas (e.g., antenna 46 and/or antenna 47). For example, the implant may be cut from a nitinol tube and a portion of the tube functions as the antenna. Alternatively, an antenna may be coupled to the implant. For some applications, the diameter of the blood vessel at the antenna is measured using the antenna. For example, impedance between the antenna and the blood vessel wall may be detected, the impedance being indicative of a level of contact between the antenna and the blood vessel wall. The diameter of the blood vessel wall at the antenna is derived from the impedance measurements.
For some applications, implant 340 detects the cardiac cycle of the subject, and provides electrical stimulation at least in part responsively to the cardiac cycle (e.g., only during systole). For some applications, implant 340 is at least partly deformable (e.g., compressible) by the wall of the blood vessel (e.g., the aorta) during the cardiac cycle. For some applications where the implant is thus deformable, and where one or more portions of the implant function as antennas, this deformation of the implant is detectable due to changes in current generated when signals 32 and/or power 132 are received by the antenna. For example, signals 32 and/or power 132 may be transmitted in pulses (e.g., at a frequency of about 5-100 Hz or 100-1000 Hz), and differences in current generated when the pulses are received are interpreted as stages in the cardiac cycle and/or as a heart rate characteristic (e.g., tachycardia, or bradycardia). Typically, but not necessarily, the deformation causes a change in the generated current due to a change in inductance of the antenna.
For some applications, implant 340 provides electrical stimulation at least in part responsively to signals 32 and at least in part responsively to the detected cardiac cycle (e.g., the implant only stimulates during systole). For some applications, external device 24 provides power 132, and implant 340 provides electrical stimulation when the implant receives the power (e.g., when the subject is close to device 24), and at least in part responsively to the detected cardiac cycle.
For some applications, a capsule is coupled to stent implant 340, and driver unit 66 is disposed within the capsule (as shown in
Reference is again made to
The applications of the invention described with reference to
Reference is now made to
Typically, electrode 219 is placed in contact with an aortic site 224 that is between the bifurcation of aorta 230 with the left subclavian artery 223 and the bifurcation of the aorta with the fifth intercostal artery 229, the aortic site being as shown in
Reference is made to
For some applications of the invention, one or more implants 40 are implanted in the vicinity of (e.g., at, or adjacent to) a respective element implantation site. Effector element 50, comprising at least one element 219 is placed (i.e., implanted) at vagal site 222. For some applications, vagal site 222 is slightly proximal to bifurcation 226. For example, vagal site 222 may be between (a) the upper junction of the left thoracic vagal trunk with the left subclavian artery, and (b) bifurcation 226. As noted above, the anatomy shown in
For some applications, aortic electrode 221 is implanted in the vicinity of a portion of the aorta that is adjacent to vagal site 222. For some applications, vagal electrode 220 is implanted on a portion of the vagus nerve that is adjacent to aortic site 224. The subject is treated by driver unit 66 of implant 40 driving a current into one or more of the electrode implantation sites. The effects of driving the current into the implantation site typically include ventricular and aortic pressure reduction, an increase in aortic compliance, a decrease in sympathetic tone, an increase in parasympathetic tone, an increase in ejection fraction, a reduction in heart rate, a reduction in left ventricular wall stress, and/or a reduction in left ventricular myocardial oxygen consumption. For some applications, the electrical stimulation reduces the likelihood of a lethal arrhythmia occurring.
For some applications, an electrode is implanted inside a vein in the vicinity of vagal site 222. For example, the electrode may be implanted in the vena cava, the innominate vein, the subclavian vein, and/or the left or right internal jugular vein. Driver unit 66 drives a current via the intravenously implanted electrode, thereby stimulating the vagal site, in accordance with the techniques described herein. Alternatively or additionally, the electrode is implanted inside an artery of the subject in the vicinity of the vagal site other than (or in addition to) the aorta, such as the pulmonary artery and/or the carotid artery, and a current is driven via the electrode in order to stimulate the vagal site. Alternatively or additionally, the electrode may be implanted at the carotid sinus, and configured to stimulate carotid baroreceptors.
Typically, the current is driven into one or both of the implantation sites, without causing a substantial change in the subject's heart rate. For some applications, there is no substantial effect on the heart rate, because the current is driven into a site that is distal to the thoracic cardiac bifurcation (i.e., the bifurcation of the vagus nerve with the thoracic cardiac branch from the left recurrent laryngeal), and therefore does not have a substantial effect on efferent fibers that directly innervate the subject's heart. (For some applications, stimulating the vagus nerve distally to the thoracic cardiac bifurcation also has a heart rate lowering effect, but it is hypothesized by the inventors that this effect is mediated through central controls rather than direct efferent stimulation of the heart.) Alternatively, the current is driven into an aortic site that is adjacent to a portion of the vagus nerve that is proximal to the thoracic cardiac bifurcation.
For some applications, aortic electrodes 221 are disposed inside the aorta (i.e., electrodes 221 are intravascular electrodes). Alternatively or additionally, the electrodes are disposed in a wall of the aorta. Further alternatively or additionally, vagal electrode 220 is a cuff-electrode (or a different design) that is placed around, or in contact with, the vagus nerve. For some applications, electrode 220 and/or electrodes 221 are chronically implanted at sites 222 and/or 224.
Typically, driver unit 66 of implant 40 drives the current into the electrode implantation site (i.e., vagal site 222 and/or aortic site 224) at least in part in response to signals 32 from external unit 24.
For some applications, driver unit 66 drives the current into the electrode implantation site in coordination with the subject's cardiac cycle and/or respiratory cycle. For example, the subject's ECG may be detected (e.g., by implant 40 and/or by external unit 24), and driver unit 66 may drive the current into the electrode implantation site responsively to the detection of the QRS complex. Alternatively or additionally, the subject's blood pressure may be measured and the current may be driven responsively thereto. For some applications, the subject's ECG, and/or the subject's blood pressure is derived from an electrical signal detected at the aorta, using electrodes 221, or a different set of electrodes (not shown). Alternatively, the current is driven independently of the subject's cardiac cycle and/or respiratory cycle.
For some applications, driver unit 66 driving current into aortic site 224, via electrodes 219, dilates the aorta by increasing nitric oxide (NO) secretion by the wall of the aorta, and/or by increasing the secretion of another vasodilation mediator from the wall of the aorta. Typically, driver unit 66 driving current into aortic site 224, via electrodes 219, inhibits the sympathetic system tone and enhances parasympathetic tone by activation of aortic afferent fibers. For some applications, driver unit 66 driving current into aortic site 224, via electrodes 219, dilates the aorta by stimulating efferent nerve ending. For some applications, driver unit 66 driving current into aortic site 224, via electrodes 219, dilates the aorta by direct electrical hyperpolarization of the vascular smooth muscle.
For some applications, driver unit 66 driving current into vagal site 222 activates afferent aortic signals traveling via the left vagus nerve thereby stimulating autonomic control centers in the central nervous system such as to enhance parasympathetic tone, thereby eliciting a parasympathetic response. For some applications, driver unit 66 driving current into aortic site 224, via electrodes 219, has a similar effect on the vagus nerve (i.e., a vagal response), due to the proximity of aortic site 224 to vagal site 222, and/or due to baroreceptor fibers or nerve endings that are located at the aortic site. For some applications, driver unit 66 driving current into the aortic site generates an aortic response, as described hereinabove, in addition to generating the aforementioned vagal response. For some applications, driver unit 66 driving the current into the aortic site stimulates autonomic control centers in the central nervous system, thereby inhibiting sympathetic tone, and inhibiting sympathetic signaling to the heart and periphery.
For some applications, driver unit 66 driving current into the aortic site, via electrode 219 reduces a ratio of a low frequency component (e.g., less than 0.05 Hz) to a high frequency component (e.g., 0.15-0.35 Hz) of heart rate variability of the subject. For some applications, driver unit 66 driving current into the aortic site, via electrode 219 reduces a ratio of a low frequency component (e.g., less than 0.05 Hz) to a high frequency component (e.g., 0.15-0.35 Hz) of blood pressure variability of the subject.
For some applications, the current has a frequency of more than 5 Hz and/or less than 150 Hz, for example, between 50 Hz and 125 Hz, such as between 100 Hz and 125 Hz. For some applications, the current has an amplitude of between 1 mA and 15 mA, for example, between 3 mA and 12 mA, such as between 7 mA and 10 mA. For some applications, a current having more than two pulses, and/or less than 40 pulses, for example, two pulses to eight pulses, or 30-40 pulses per cardiac cycle, is driven into the aorta. In accordance with respective applications, the current is delivered continuously or intermittently.
For some applications, vagal site 222 is alternatively or additionally mechanically stimulated by implant 40, for example, by mechanically stimulating the vagus nerve at the vagal site, and/or by mechanically stimulating aortic site 224, such that the vagal site also becomes stimulated. For some applications, the vagal site is alternatively or additionally stimulated by implant 40 using the one or more mechanical stimulators described hereinabove (e.g., with reference to
Reference is again made to
The hypothesized effects of the stimulation of vagal site 222 and/or aortic site described with reference to
It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.
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| Number | Date | Country | |
|---|---|---|---|
| 20130123880 A1 | May 2013 | US |
| Number | Date | Country | |
|---|---|---|---|
| 61532660 | Sep 2011 | US |
