The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 17 No. 3 • April 2014


Remote Ischemic Conditioning

Could It Be an Exercise Mimic?

Reducing Damage Done by Evolving Heart Attack
with Simple Inexpensive Method

A safe, simple, and effective way to reduce the damage resulting from an ongoing heart attack called remote ischemic preconditioning has been described in the Feb. 27, 2010 Lancet.1 A variation of this method, called Enhanced External Counterpulsation (EECP), is used at the Whitaker Wellness Center* in their program of treating patients with cardiovascular disease. A similar device is used at some hospitals to decrease the risk of blood clots in patients bedridden following major surgery.


*Whitaker Wellness Center (www.whitakerwellness.com), 1-800-488-1500; reported by Julian Whitaker, M.D., Director of the Whitaker Wellness Center, to stimulate the formation of collateral circulation (new blood vessels) around clogged arteries. (Improved collateral circulation is also an effect induced by exercise.)

†Sandy was hooked up to such a device at the Mayo Clinic following her surgery for bowel obstruction about two years ago. Her legs were cyclically pulsed to compress and then the pressure released for decompression to take place. This was a very pleasant, enjoyable form of massage to help prevent blood clots in a patient stuck in bed. For use as a device to reduce the risk of blood clots, this would be considered a medical device and regulated by the FDA. It would cost a lot less as a device for massaging the legs that could do the same thing mechanistically but not be regulated as a medical device. Such devices are available via Amazon.com.


The Lancet Study Reported Significantly Less Heart Damage in Heart Attack Patients

The study1 followed 126 patients being taken to the hospital by ambulance. During the trip (following oral administration of aspirin or i.v. clopidogrel along with heparin, acting as anticlotting agents), these individuals were administered remote ischemic conditioning followed (at the hospital) by percutaneous angioplasty or percutaneous angioplasty without remote ischemic conditioning.

The remote ischemic conditioning procedure was very simple and could even be done by laypersons: a blood pressure cuff was attached to the upper arm and then subjected to four cycles of 5 minutes inflation followed by 5 minutes deflation. You pump up the cuff until circulation to the arm is cut off for 5 minutes (cuff pressure above systolic peak) then deflate it for 5 minutes. Repeat three more times. Very simple, safe, and easy.

The primary endpoint was myocardial salvage index at 30 days after percutaneous angioplasty, estimated by gated single photon emission CT. Salvage (heart cells protected against dying) as a percentage of the left ventricle was significantly higher in the intervention group (16%, 8–24, n=82) than in the control group (11%, 3–22, n=83; p=0.0391).

Heart Damage Reduced by Remote Ischemic Conditioning in Patients Undergoing Coronary Artery Bypass Graft Surgery

Another paper1B reported on a similar experimental protocol in patients undergoing coronary artery bypass graft surgery just after the induction of anesthesia. They were administered remote ischemia conditioning similar to that received by the patients described above.1 These patients1B received three cycles of right upper limb ischemia by a cuff-inflator; 5 min. inflation to 200 mm Hg was followed by 5 min. of reperfusion (the cuff was deflated). In these patients, the levels of serum troponin T were measured to detect heart injury before surgery and at 6, 12, 24, 48, and 72 hours after surgery. (Increased troponin T is typically detected in those suffering heart attacks; it is a protein released from dead muscle cells.) Remote ischemic preconditioning significantly reduced overall serum troponin T release at 6, 12, 24, and 48 hours after surgery. “The total area under the curve was reduced by 43% from 36.12 μg/L (SD 26.08) in the control group to 20.58 μg/L (9.58) in the remote ischemic preconditioning group …” The mean difference was 15.55 (SD 5.32; 95% CI 4.88 – 26.21, p=0.005). Thus, this very simple, safe technique significantly reduced heart damage that occurs in the hearts of patients undergoing coronary artery bypass graft surgery that has been a matter of considerable concern since these patients already have damaged hearts.

Mechanisms That May Be Responsible for the Protective Effect of Remote Ischemic Conditioning

A number of mechanisms for the effects of remote ischemic conditioning have been proposed: upregulation of IL-6,2 activation of the potassium ATP channel which then induces the generation of reactive oxygen species and nitric oxide, both of which are required for preconditioning protection,3 and mediation by opioid receptors has also been suggested.4

Could Remote Ischemic Conditioning Mimic Exercise?

It is interesting to note that the mechanisms proposed as being responsible for remote ischemic conditioning are all mechanisms that may be (at least in part) responsible for the beneficial effects of exercise.2B Therefore, we are wondering whether this simple technique of cyclically inflating and then deflating a blood pressure cuff could act as an exercise mimic, allowing even the most sedentary of us to “exercise” daily virtually without effort. One could simply read, watch TV, or just relax during the procedure to get a daily “dose” of simulated exercise.

In support of the hypothesis that remote ischemic conditioning may improve nitric oxide availability are data from a study of the variability in uptake efficiency for pulsed versus constant concentration delivery of inhaled nitric oxide.5 This study showed that pulsed nitric oxide delivery via inhalation of nitric oxide improved uptake efficiency compared with constant concentration delivery. Although the study involved inhalation of nitric oxide gas rather than induced release of nitric oxide by remote ischemic conditioning (as described above), the improved efficiency of pulsed nitric oxide release as compared to constant release may be similar. Additionally, the nitric oxide release by remote ischemic conditioning has been found to be a safe technique for increasing nitric oxide, whereas the paper on nitric oxide inhalation indicated the need for careful control of the amount and timing of the nitric oxide to achieve optimal delivery of nitric oxide. This shouldn’t be a concern with remote ischemic conditioning, where natural regulatory processes control the release of nitric oxide.

Another paper6 from 2000 suggested in its “speculative review” that vascular pulsations in mild exercise that stimulate nitric oxide release may be a source of some of the beneficial effects in exercise. The authors surmised that eNOS activation by acute changes in pulsatile pressure (or shear stress) is the cause of the pulsatile release of nitric oxide. “In doing this, the restoration of NO balance may serve to decrease the presence of free radicals, allowing the vascular endothelium to return to a state of inhibition while simultaneously protecting sympathetic nerve endings.” We found this paper surprisingly ahead of its time and think their suggested mechanism for beneficial effects of mild exercise via pulsatile nitric oxide release is a plausible one. If so, the use of a system to produce pulsatile compression and decompression of skeletal muscle via inflation/deflation of a blood pressure cuff with release of pulses of nitric oxide is, we think, likely to act as an exercise mimic.

References

1. Botker 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. 375:727-34 (2010).
1B. Hausenloy et al. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet. 370:575-9 (2007)
2. Tacchini et al. Up regulation of IL- 6 by ischemic preconditioning in normal and fatty rat livers: association with reduction of oxidative stress. Free Radic Res. 40(11):1206-17 (2006).
2B. Keller et al. Interleukin-6 receptor expression in contracting human skeletal muscle: regulating role of IL-6. FASEB J. 19:1181-3 (2005).
3. Lebuffe et al. ROS and NO trigger early preconditioning: relationship to mitochondrial KATP channel. Am J Physiol Heart Circ Physiol. 284:H299-H308 (2003).
4. Weber. Receptor cross-talk in remote conditioning. Nat Med. 16(7):760-2 (2010).
5. Martin et al. Variability in uptake efficiency for pulsed versus constant concentration delivery of inhaled nitric oxide. Med Gas Res. (open access) 4:1 (2014) doi:10.1186/2045-9912-4-1.

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