This invention relates generally to systems for performing remote ischemic conditioning, and more particularly, to systems for performing remote ischemic conditioning incorporating a removable controller.
Ischemic diseases are significant causes of mortality in industrialized nations. It is well established that tissue damage results from ischemia (insufficient blood flow to a tissue) followed by reperfusion (reflow of blood to the tissue). Ischemia and reperfusion cause disturbance of microcirculation with ensuing tissue damage and organ dysfunction. Organs such as the kidney, heart, liver, pancreas, lung, brain and intestine are known to sustain damage following ischemia and reperfusion.
In ischemic conditioning (IC), a tissue or organ or region of a subject's body is deliberately subjected to brief ischemic episodes, followed by brief reperfusion episodes. IC has been found to render the tissue, organ or region resistant to injury during subsequent ischemic episodes. The phenomenon of ischemic conditioning has been demonstrated in most mammalian tissues. IC is now recognized as one of the most potent innate protective mechanisms against ischemia-reperfusion (I-R) injury.
Remote ischemic conditioning (RIC) refers to the deliberate induction of transient ischemia in a subject at a region remote from at least some of the tissue to be protected. Often, RIC includes inducing transient ischemia in a subject's limb to protect organs remote from the limb, such as the myocardium. Myocardial protection has been demonstrated by a variety of remote stimuli, including renal ischemia, liver ischemia, mesenteric artery ischemia, and skeletal muscle hind limb ischemia.
RIC, in the broadest sense, involves deliberate induction of an ischemic period followed by a reperfusion period. The ischemic period may involve complete cessation of blood flow (blood flow occlusion). Such ischemic periods may be induced by applying super-systolic pressures on a region of the body, such as for example a limb. Alternatively, ischemic periods may also be induced by applying a less than systolic pressure.
RIC may be performed prior to (pre-), during (per-) and/or following (post-) an ischemic injury or other injury which benefits from RIC. RIC has shown benefit in reducing or preventing damage resulting from, myocardial infarction and trauma, inter alia,
In one aspect, a device for performing RIC includes an inflatable cuff configured to encircle a limb of a subject and a controller removably attached to the cuff. The controller includes a pump; a manifold in fluid communication with the pump; an outlet in fluid to communication with the manifold and in removable fluid communication with the inflatable cuff; a pressure sensor; and a control circuit configured to implement a RIC treatment protocol.
In another aspect, a cuff assembly may be adapted to encircle a limb of a subject. The cuff assembly includes an inner layer, an outer layer, and a bladder disposed between the inner layer and the outer layer. The outer layer includes two flexible foam sections spaced apart in a longitudinal direction of the cuff assembly. The outer layer also includes an intermediate section disposed between the two flexible foam sections. The intermediate section may have a greater rigidity than the two flexible foam sections.
In a further aspect, a device includes an inflatable cuff and a controller attachment section. The inflatable cuff may be configured to encircle a limb of a subject. The cuff has an axial direction substantially parallel to an axis of the limb when the cuff is in the fitted state.
The controller attachment section may be operatively attached to the cuff by at least one attachment joint oriented substantially parallel to the axial direction of the cuff. The controller attachment section may include a connector adapted for removable attachment of a controller. The controller attachment section may provide fluid communication between the controller and cuff in a location removed from the connector when the controller is in an attached state.
It should be appreciated that all combinations of the foregoing aspects and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the inventive subject matter disclosed herein.
The foregoing and other aspects, embodiments, and features of the present teachings can be more fully understood from the following description in conjunction with the accompanying drawings.
The accompanying drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component that is illustrated in various figures is represented by a like numeral. For purposes of clarity, not every component may be labeled in every drawing. Various embodiments of the invention will now be described, by way of example, with reference to the accompanying drawings, in which:
The illustrative embodiments described herein are not necessarily intended to show all aspects of the invention. Aspects of the invention are not intended to be construed narrowly in view of the illustrative embodiments. It should be appreciated that the various concepts and embodiments introduced above and those discussed in greater detail below may be implemented in any of numerous ways, as the disclosed concepts and embodiments are not limited to any particular manner of implementation. In addition, it should be understood that aspects of the invention may be used alone or in any suitable combination with other aspects of the invention.
In one aspect, a system for performing RIC includes an inflatable cuff, a controller attachment section joined to the cuff, and a controller selectively removable from the controller attachment section. The controller may control the inflation and deflation of the inflatable cuff. Furthermore, the controller may include a control circuit programmed to implement an RIC protocol. In another aspect the cuff may be soft, rigid, and made from thermoformable materials.
Turning now to the figures, several possible embodiments are described in further detail.
In one aspect, cuff 4 is axially rigid while being soft or non-irritating to the skin. In one embodiment, cuff 4 may include an inner layer 16, a layer 18, and a selectively inflatable bladder 20 disposed between layers 16 and 18, as depicted in
In some embodiments, cuff 4 may include two sections 22 spaced apart in a to longitudinal direction and an intermediate section 24 disposed between the sections 22. Intermediate section 24 may be constructed to have a greater rigidity than sections 22. The increased rigidity of the intermediate section 24 may be created either by an inherent material property difference, a difference in the physical construction (e.g. a thicker section and/or inclusion of reinforcing features), or both. In one embodiment, the intermediate section 24 may include a substantially flat outer surface 25 for attachment to the controller attachment section 6. Intermediate section 24 may also include an inner surface 26 which is curved in the longitudinal direction of the cuff 4. The curved inner surface 26 may be constructed so as to generally conform to the curvature of a limb. In some embodiments, the size and curvature of the cuff 4 may be suited for a variety of sizes and ages of patients ranging from neonates to obese adults. The cuff 4 may also be sized for either attachment to an arm or a leg. The intermediate section 24 may be constructed from thermosetting plastics, thermoforming plastics, and/or foamed materials. Sections 22 and the intermediate section 24 may be integrally formed with one another, or they may be formed separately and subsequently joined using any appropriate method including, but not limited to, a sewn seam, ultrasonic welds, adhesives, rivets, clamping structures, and/or mechanically interlocking features. Section 22 may be formed of a foam material or any other suitably flexible yet strong material.
In one embodiment, cuff 4 may also include a plurality of reinforcing structures 28 substantially aligned in the axial direction of the cuff assembly. Reinforcing structures 28 typically may be formed in outer layer 18 of sections 22. Reinforcing structures 28 provide axial rigidity to the cuff 4. The increased axial rigidity provided by reinforcing structures 28 helps to distribute the pressure applied by cuff 4 in the axial direction to provide a substantially uniform pressure across the axial width of the cuff 4. Reinforcing structures 28 may also help to prevent kinks in cuff 4 when it is placed around the arm or leg of an individual. Reinforcing structures 28 may be spaced apart in a longitudinal direction to permit the cuff 4 to easily bend around an encircled limb while still providing increased axial rigidity. Reinforcing structures 28 may be curved or straight in shape in the axial direction. In some embodiments, the reinforcing structures 28 may be integrally formed with the foam in sections 22 such as by the application of heat and/or pressure (e.g. thermoforming) to selectively melt and/or compress portions of the foam in sections 22. The uncompressed and/or unmelted portions of foam in sections 22 form the raised reinforcing structures 28. Alternatively, reinforcing structures 28 may be separately formed and subsequently joined to sections 22.
Layer 18 may also include a cloth layer 19 applied to an exterior surface. Cloth layer 19 may be formed of a low stretch or non-stretch cloth. The low stretch or non-stretch properties may be an inherent property of the cloth selected. Alternatively, cloth layer 19 may be a made from thermoformable materials and may be laminated to the exterior surface of layer 18. The lamination process may alter the thermoformable fabric to be a low stretch or non-stretch material. In one embodiment, the cloth may be applied to and laminated with layer 18 in a flat layout prior to forming reinforcing structures 28. Reinforcing structures 28 may subsequently be thermoformed to a final desired shape. The resulting sections 22 may be soft and have low stretch or non-stretch properties. Furthermore, sections 22 may be thermoformable enabling subsequent processing steps.
Selectively inflatable bladder 20 may be disposed between inner layer 16 and layer 18. Bladder 20 may have a valve 30 arranged and adapted to provide a fluid inlet to the interior of bladder 20. Valve 30 extends through a hole 32 in the intermediate section 24 of cuff 4. Valve 30 may be placed in sealed fluid communication with a corresponding structure 33 on controller attachment section 6 which may also be in sealed fluid communication with an outlet 48 of controller 8. When connected to outlet 48 of controller 8 through structure 33 of the controller attachment section 6, valve 30 may provide pressurized gas such as air to bladder 20. In some embodiments, bladder 20 may be a component separate from layers 16 and 18. Bladder 20 may be formed such as by bonding two separate sheets of thermoplastic polyurethane together. In other embodiments, bladder 20 may be formed from air impermeable layers incorporated into layers 16 and 18 of cuff 4. Layers of bladder 20 may be bonded together in an air tight manner using any number of methods including adhesives, ultrasonic welding, beads of material around the edges, and/or other appropriate methods as would be apparent to one of skill in the art. Bladder 20 may also be formed as a unitary structure without separate layers.
Layers 16, 18, 19, and bladder 20 of cuff 4 may be held together at their edges in any suitable fashion, such as by a binding material 36 wrapped around the edge of cuff 4 and sewn to cuff 4, as shown in
The cuff 4 may also include fasteners to hold the cuff on a limb of a subject and to adjust the circumferential size of the cuff 4 when in the fitted state. Such fasteners include, but are not limited to, hook and loop fasteners, latches, ratchet mechanisms, clasps, snaps, buckles, and other appropriate structures as would be apparent to one of skill in the art. For example, the fastener may be a hook and loop fastener including a plurality of adjacent unconnected hook sections 38a disposed on layer 18 or 19 and loop sections 38b disposed on inner layer 16. Hook sections 38a may extend in the axial direction of the cuff 4. The width of each hook section 38a, with respect to the longitudinal direction of the cuff, may be selected to provide a flexible cuff able to wrap around different sized limbs.
The controller attachment section 6 of
In one embodiment, lower surface 44 and/or bottom edge 46 of controller attachment section 6 may be disposed on and substantially conform to the shape of an outer surface of cuff 4. In some embodiments, bottom surface 44 and/or bottom edge 46 of the controller attachment section 6 may be disposed on and substantially conform to the shape of outer surface 25 of intermediate section 24 of cuff 4 shown in
As shown in
As shown in
The internal components of controller 8 are best shown in
The control circuit of PCB 66 may be programmed with certain error conditions which may cause the procedure to be aborted or which may cause an indication of the error to appear on a display or which can be used in other known ways. These error conditions may include, but are not limited to: the cuff is not pressurized within a predefined period, such as 20 seconds, 30 seconds, 40 seconds, 50 seconds, or one minute; there is no communication between pump 62 and PCB 66 upon start up; there is no communication between pump 62 and PCB 66 for more than a predefined period, such as two, three, four, or five seconds; multiple consecutive repumps are needed to maintain cuff pressure; pump 62 continues to run and does not respond to an abort signal after a predefined number of retrys, such as three, four, or five retrys; pressure in cuff 4 is not near zero gage pressure within a predefined period, such as 20 seconds, 30 seconds, 40 seconds, 50 seconds, or one minute after the end of an inflation cycle; pressure in cuff 4 is above a predetermined pressure such as 200, 220, 240 or 260 mmHg for longer than a predefined period, such as 5, 10, 20, or 30 seconds; and the pump 62 CPU does not wake up after a command is sent to it by the control circuit. The error condition may be cleared and/or the system may be reset such as by pressing a stop button 76 on the face of controller 8.
During usage, controller 8 may be attached to controller attachment section 6 to place controller outlet 48 into fluid communication with cuff 4. Pressurized gas may then be pumped through controller outlet 48 to inflate the cuff 4. The cuff pressure may be controlled by selectively opening valve 68 in response to a command from the control circuitry of PCB 66. In some embodiments, valve 68 may include a pressure safety relief feature that opens valve 68 in response to an over pressure event during an RIC treatment. In one embodiment, valve 68 opens when the pressure in cuff 4 exceeds 260 mmHg Valve 68 may open in response to either an error command from the control circuitry of PCB 66, or the valve 68 may include an automatically actuated mechanical system. Controller 8 may also include a slow continuous relief valve. Such a valve would continuously release gas from inflated bladder 20 at a selected rate lower than the rated flow rate of the pump 62. The slow continuous release of gas from bladder 20 could be used to deflate bladder 20 in case of a mechanism failure.
In some embodiments, the control circuit of PCB 66 may be programmable by a health professional and/or an end user according to a prescribed treatment protocol. Alternatively, the control circuit may only be programmed at the factory and may not be altered afterwards by the end user. The control circuitry may also include non-volatile memory for the logging and storage of treatment history. A health care professional may be able to access this memory to determine the treatment history of a patient and determine compliance with a prescribed treatment regime. In another embodiment, the controller may send this information via wireless, or hard wired, communication to a separate receiver for patient records, monitoring, or call center purposes. In one embodiment, controller 8 may include a start button 74 and stop button 76. In some embodiments, the start and stop buttons 74 and 76 may be incorporated into a single button. Controller 8 may also include a hard wired and/or emergency stop button and/or a quick release valve (not shown). In other embodiments, other controls may be included to allow expanded control of an RIC treatment.
In addition to controls, controller 8 may include displays related to the current cycle, the number of cycles left in a treatment, whether the treatment is completed, error signals, charge of the system, and other relevant information. In one embodiment, controller 8 may include a cycle time display 78. Cycle time display 78 may indicate the remaining portion of the inflation/deflation cycle by using illuminated indicators 78a arranged in a circular pattern corresponding to a full inflation/deflation cycle. Each indicator 78a of cycle time display 78 may correspond to a set fraction of the inflation/deflation cycle. When all of the indicators 78a of cycle time display 78 are illuminated, the inflation/deflation cycle is complete. Alternatively, the indicators 78a of cycle time display 78 may start a cycle fully illuminated and sequentially turn off as the cycle proceeds. When each indicator 78a of cycle time display 78 is dark, the particular inflation/deflation cycle is complete. While a circular display has been disclosed, cycle time display 78 could also be arranged in other linear, or non-linear, shapes corresponding to a full cycle. Controller 8 may also include a current cycle display 80, or a digital numeric display, indicating whether the current cycle is the first, second, third, or to other cycle. A procedure complete indicator 82 may be illuminated with a solid color or it may blink when the RIC treatment is complete to indicate the end of the procedure. An error display 84 may indicate when an error has occurred by blinking or being fully illuminated. Alternatively, error display 84 may blink in a preset pattern or display a particular color to indicate which error has occurred. A battery charge indicator 86 may indicate the approximate charge remaining in the batteries 70, and may also signal that that the remaining charge is only sufficient for one cycle by blinking.
The above described system may be used for implementing an RIC treatment. The treatment includes placing cuff 4 on a limb of a user and attaching controller 8 to controller attachment section 6 on cuff 4. A user may then press start button 74 to initiate the treatment. Once started the control circuitry of PCB 66 monitors the pressure sensor and turns pump 62 on to inflate the cuff 4. The pressure is then increased to a desired pressure, such as a blood flow occlusion pressure. In one embodiment, the control circuitry of PCB 66 maintains the cuff pressure between preselected pressure limits such as 200 mmHg to 210 mmHg In other embodiments, the control circuitry of PCB 66 may first determine a systolic blood pressure. After determining a systolic blood pressure, the control circuitry of PCB 66 may subsequently initiate the RIC treatment protocol with a desired pressure such as a pressure greater than the measured systolic blood pressure. Regardless of the specific pressure used, the pressure may be maintained for a selected ischemic duration. Ischemic durations may last on the order of seconds or minutes. After completing the ischemic duration, the controller may activate valve 68 to deflate cuff 4 and initiate the reperfusion duration. Reperfusion durations generally last for at least a minute, although shorter reperfusion durations may be used. After completion of the reperfusion duration another RIC cycle may be conducted. An RIC treatment may include a single cycle or multiple cycles. In one embodiment, an RIC treatment may include four cycles with ischemic durations of approximately 5 minutes, and reperfusion durations of approximately 5 minutes. At the end of the last cycle the cuff 4 may deflate within 30 seconds and the controller 8 may confirm a near zero gage pressure prior to shutting down.
In some embodiments, controller 8 may be charged using a charging cradle 88, as shown in
While the present teachings have been described in conjunction with various embodiments and examples, it is not intended that the present teachings be limited to such embodiments or examples. On the contrary, the present teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art. Accordingly, the foregoing description and drawings are by way of example only.
Number | Name | Date | Kind |
---|---|---|---|
3552383 | Krueger et al. | Jan 1971 | A |
4106002 | Hogue, Jr. | Aug 1978 | A |
4206764 | Williams | Jun 1980 | A |
4321929 | Lemelson et al. | Mar 1982 | A |
4664651 | Weinshenker et al. | May 1987 | A |
4690151 | Utsunomiya et al. | Sep 1987 | A |
4967758 | Masciarotte | Nov 1990 | A |
5072736 | Ogawa et al. | Dec 1991 | A |
5135003 | Souma | Aug 1992 | A |
5201758 | Glover | Apr 1993 | A |
5267565 | Beard et al. | Dec 1993 | A |
5569304 | Ulrich | Oct 1996 | A |
5571075 | Bullard et al. | Nov 1996 | A |
5634467 | Nevo | Jun 1997 | A |
5643315 | Daneshvar | Jul 1997 | A |
5651369 | Tomita | Jul 1997 | A |
6152881 | Raines et al. | Nov 2000 | A |
6210423 | Kim et al. | Apr 2001 | B1 |
6245023 | Clemmons | Jun 2001 | B1 |
6251080 | Henkin et al. | Jun 2001 | B1 |
6344025 | Inagaki et al. | Feb 2002 | B1 |
6485429 | Forstner | Nov 2002 | B2 |
6550482 | Burbank et al. | Apr 2003 | B1 |
6626840 | Drzewiecki et al. | Sep 2003 | B2 |
6702720 | Dardik | Mar 2004 | B2 |
6719704 | Narimatsu et al. | Apr 2004 | B2 |
6858012 | Burns et al. | Feb 2005 | B2 |
6905456 | Brunner et al. | Jun 2005 | B1 |
6962599 | Hui et al. | Nov 2005 | B2 |
7004907 | Banet et al. | Feb 2006 | B2 |
7018335 | Kario et al. | Mar 2006 | B2 |
7048702 | Hui | May 2006 | B2 |
7111346 | Inman et al. | Sep 2006 | B2 |
7166077 | Millay et al. | Jan 2007 | B2 |
7228576 | Inman et al. | Jun 2007 | B2 |
7314478 | Hui | Jan 2008 | B2 |
7338410 | Dardik et al. | Mar 2008 | B2 |
7374540 | Schnall et al. | May 2008 | B2 |
7390303 | Dafni | Jun 2008 | B2 |
7404221 | Sackner | Jul 2008 | B2 |
7427268 | Millay et al. | Sep 2008 | B2 |
7485131 | Hovanes et al. | Feb 2009 | B2 |
7689286 | Pastore et al. | Mar 2010 | B2 |
7717855 | Caldarone et al. | May 2010 | B2 |
7885710 | Sih et al. | Feb 2011 | B2 |
8114026 | Leschinsky | Feb 2012 | B2 |
8246548 | Naghavi | Aug 2012 | B2 |
20010029389 | Kim et al. | Oct 2001 | A1 |
20030013974 | Natarajan et al. | Jan 2003 | A1 |
20030065270 | Raines et al. | Apr 2003 | A1 |
20030176795 | Harris et al. | Sep 2003 | A1 |
20030216651 | Burns et al. | Nov 2003 | A1 |
20030233118 | Hui | Dec 2003 | A1 |
20040044290 | Ward et al. | Mar 2004 | A1 |
20040064076 | Bilgi et al. | Apr 2004 | A1 |
20040102818 | Hakky et al. | May 2004 | A1 |
20040241634 | Millis et al. | Dec 2004 | A1 |
20040255956 | Vinten-Johansen | Dec 2004 | A1 |
20050004476 | Payvar et al. | Jan 2005 | A1 |
20050070405 | Egger | Mar 2005 | A1 |
20050159640 | Barbut et al. | Jul 2005 | A1 |
20050171444 | Ono et al. | Aug 2005 | A1 |
20050177078 | Loeb et al. | Aug 2005 | A1 |
20060052712 | Poliac et al. | Mar 2006 | A1 |
20060052713 | Poliac et al. | Mar 2006 | A1 |
20060052714 | Poliac et al. | Mar 2006 | A1 |
20060058717 | Hui et al. | Mar 2006 | A1 |
20060100639 | Levin et al. | May 2006 | A1 |
20060142663 | Sawanoi et al. | Jun 2006 | A1 |
20070005106 | Adducci | Jan 2007 | A1 |
20070055188 | Avni et al. | Mar 2007 | A1 |
20070135836 | McEwen et al. | Jun 2007 | A1 |
20070150005 | Sih et al. | Jun 2007 | A1 |
20070247304 | Bonnefin et al. | Oct 2007 | A1 |
20080077176 | Hanlon et al. | Mar 2008 | A1 |
20080139949 | Caldarone et al. | Jun 2008 | A1 |
20080222769 | Natonson et al. | Sep 2008 | A1 |
20090036785 | Danielsson | Feb 2009 | A1 |
20090124912 | McEwen et al. | May 2009 | A1 |
20090137884 | Naghavi et al. | May 2009 | A1 |
20090287069 | Naghavi et al. | Nov 2009 | A1 |
20090318818 | Whitaker et al. | Dec 2009 | A1 |
20090324748 | Dobson | Dec 2009 | A1 |
20100081941 | Naghavi et al. | Apr 2010 | A1 |
20100081977 | Vess | Apr 2010 | A1 |
20100105993 | Naghavi et al. | Apr 2010 | A1 |
20100160799 | Caldarone et al. | Jun 2010 | A1 |
20100185220 | Naghavi et al. | Jul 2010 | A1 |
20100186752 | Rixson | Jul 2010 | A1 |
20100268130 | Khan | Oct 2010 | A1 |
20100292619 | Redington et al. | Nov 2010 | A1 |
20100305607 | Caldarone et al. | Dec 2010 | A1 |
20100322467 | Reed et al. | Dec 2010 | A1 |
20100324429 | Leschinsky | Dec 2010 | A1 |
20100328142 | Zoughi et al. | Dec 2010 | A1 |
20110077566 | Ganapathy | Mar 2011 | A1 |
20110190807 | Redington et al. | Aug 2011 | A1 |
20110238107 | Raheman | Sep 2011 | A1 |
20110240043 | Redington | Oct 2011 | A1 |
20110251635 | Caldarone | Oct 2011 | A1 |
20120130419 | Leschinsky | May 2012 | A1 |
Number | Date | Country |
---|---|---|
20082012363 | Nov 2008 | CN |
0 960 598 | Dec 1999 | EP |
1016379 | May 2000 | EP |
1 249 218 | Oct 2002 | EP |
1323365 | Jul 1973 | GB |
2001221 | Jan 1990 | JP |
07-051276 | Feb 1995 | JP |
2001505472 | Apr 2001 | JP |
2002539879 | Nov 2002 | JP |
2 253 429 | Jun 2005 | RU |
WO 8300995 | Mar 1983 | WO |
WO 9118571 | Dec 1991 | WO |
WO 9830144 | Jul 1998 | WO |
WO 0057776 | Oct 2000 | WO |
WO 2005011503 | Feb 2005 | WO |
WO 2005077265 | Aug 2005 | WO |
WO 2006024871 | Mar 2006 | WO |
WO 2006030441 | Mar 2006 | WO |
WO 2006061825 | Jun 2006 | WO |
WO 2007085828 | Aug 2007 | WO |
WO 2008148045 | Dec 2008 | WO |
WO 2008148062 | Dec 2008 | WO |
Entry |
---|
Search Report from PCT Application No. PCT/US2012/033442, Jun. 12, 2012. |
Written Opinion from PCT Application No. PCT/US2012/033442, Jun. 12, 2012. |
Ali et al., Remote ischemic preconditioning reduces myocardial and renal injury after elective abdominal aortic aneurysm repair: a randomized controlled trial. Circulation. Sep. 11, 2007;116(11 Suppl):I98-105. |
Bartekova et al., Liver ischemia induced remote preconditioning: role of cardioprotective proteins. 25. ISHR-ES meeting. Jun. 21-25, 2005. Tromsoe, Norway. J Mol Cell Cardiol. 2005;38(6):1004. |
Bøtker et al., Upper-limb ischemia during ambulance transfer reduces myocardial perfusion injury in STEMI. Heartwire. Mar. 28, 2009. Featured at i2 Session of AAC. Mar. 28-31, 2009. Last Accessed on Mar. 5, 2012 from http://www.theheart.org/article/951627.do. |
Bøtker et al., Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet. Feb. 27, 2010;375(9716):727-34. |
Brzozowski et al., Ischemic preconditioning of remote organs attenuates gastric ischemia-reperfusion injury through involvement of prostaglandins and sensory nerves. Eur J Pharmacol. Sep. 19, 2004;499(1-2):201-13. |
Cheung et al., Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J Am Coll Cardiol. Jun. 6, 2006;47(11):2277-82. |
Dickson et al., Rabbit heart can be “preconditioned” via transfer of coronary effluent. Am J Physiol. Dec. 1999;277(6 Pt 2):H2451-7. |
Dong et al., Limb ischemic preconditioning reduces infarct size following myocardial ischemia-reperfusion in rats] Sheng Li Xue Bao. Feb. 25, 2004;56(1):41-6. Chinese. |
Gho et al., Myocardial protection by brief ischemia in noncardiac tissue. Circulation. Nov. 1, 1996;94(9):2193-200. |
Hausenloy et al., Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet. Aug. 18, 2007;370(9587):575-9. |
Hausenloy et al., Preconditioning and postconditioning: underlying mechanisms and clinical application. Atherosclerosis. Jun. 2009;204(2):334-41. Epub Nov. 5, 2008. |
Hausenloy et al., The therapeutic potential of ischemic conditioning: an update. Nat Rev Cardiol. Jun. 21, 2011;8(11):619-29. |
Hoole et al., Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial. Circulation. Feb. 17, 2009;119(6):820-7. Epub Feb. 2, 2009. |
Jenkins et al., Ischaemic preconditioning reduces troponin T release in patients undergoing coronary artery bypass surgery. Heart. Apr. 1997;77(4):314-8. |
Kharbanda et al., Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo. Circulation. Mar. 27, 2001;103(12):1624-30. |
Kharbanda et al., Remote ischaemic preconditioning protects against cardiopulmonary bypass-induced tissue injury: a preclinical study. Heart. Oct. 2006;92(10):1506-11. Epub Jul. 3, 2006. |
Kharbanda et al., Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation. Dec. 3, 2002;106(23):2881-3. |
Konstantinov et al., Remote ischemic preconditioning of the recipient reduces myocardial ischemia-reperfusion injury of the denervated donor heart via a Katp channel-dependent mechanism. Transplantation. Jun. 27, 2005;79(12):1691-5. |
Konstantinov et al., The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans. Physiol Genomics. Sep. 16, 2004;19(1):143-50. Epub Aug. 10, 2004. |
Konstantinov et al., The remote ischemic preconditioning stimulus modifies gene expression in mouse myocardium. J Thorac Cardiovasc Surg. Nov. 2005;130(5):1326-32. |
Lang et al., Myocardial preconditioning and remote renal preconditioning—identifying a protective factor using proteomic methods? Basic Res Cardiol. Mar. 2006;101(2):149-58. Epub Nov. 11, 2005. |
Laskey et al., Frequency and clinical significance of ischemic preconditioning during percutaneous coronary intervention. J Am Coll Cardiol. Sep. 17, 2003;42(6):998-1003. |
Leesar et al., Nonelectrocardiographic evidence that both ischemic preconditioning and adenosine preconditioning exist in humans. J Am Coll Cardiol. Aug. 6, 2003;42(3):437-45. |
Leesar et al., Preconditioning of human myocardium with adenosine during coronary angioplasty. Circulation. Jun. 3, 1997;95(11):2500-7. |
Loukogeorgakis et al., Remote ischemic preconditioning provides early and late protection against endothelial ischemia-reperfusion injury in humans: role of the autonomic nervous system. J Am Coll Cardiol. Aug. 2, 2005;46(3):450-6. |
McCully et al., Adenosine-enhanced ischemic preconditioning: adenosine receptor involvement during ischemia and reperfusion. Am J Physiol Heart Circ Physiol. Feb. 2001;280(2):H591-602. |
Murry et al., Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. Nov. 1986;74(5):1124-36. |
Nandagopal et al., Critical role for nitric oxide signaling in cardiac and neuronal ischemic preconditioning and tolerance. J Pharmacol Exp Ther. May 2001;297(2):474-8. |
Peng et al., The protective effects of ischemic and calcitonin gene-related peptide-induced preconditioning on myocardial injury by endothelin-1 in the isolated perfused rat heart. Life Sci. 1996;59(18):1507-14. |
Penttila et al., Ischemic preconditioning does not improve myocardial preservation during off-pump multivessel coronary operation. Ann Thorac Surg. Apr. 2003;75(4):1246-52; discussion 1252-3. |
Peralta et al., Liver ischemic preconditioning: a new strategy for the prevention of ischemia-reperfusion injury. Transplant Proc. Aug. 2003;35(5):1800-2. |
Przyklenk et al., Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. Mar. 1993;87(3):893-9. |
Schmidt et al., Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning. Am J Physiol Heart Circ Physiol. Apr. 2007;292(4):H1883-90. Epub Dec. 15, 2006. |
Schoemaker et al., Bradykinin mediates cardiac preconditioning at a distance. Am J Physiol Heart Circ Physiol. May 2000;278(5):H1571-6. |
Tomai et al., Ischemic preconditioning in humans: models, mediators, and clinical relevance Circulation. Aug. 3, 1999;100(5):559-63. |
Wolfrum et al., Calcitonin gene related peptide mediates cardioprotection by remote preconditioning. Regul Pept. Apr. 15, 2005;127(1-3):217-24. |
Tejwani NC et al., “Tourniquet Cuff Pressure: The Gulf Between Science and Practice,” J. Trauma, 61 (6), pp. 1415-1418, Dec. 2006. |
Product ad by Delfi Medical Innovations, Inc., (Delfi tourniquet)(2011). |
Takarada et al., “Applications of Vascular Occlusion Diminish Disuse Atrophy of Knee Extensor Muscles,” Official Journal of the American College of Sports Medicine, Medicine and Science in Sports and Exercise, pp. 2035-2039 (Apr. 2000). |
May 29, 2013 Office Action from U.S. Appl. No. 13/542,929. |
Number | Date | Country | |
---|---|---|---|
20120265240 A1 | Oct 2012 | US |