The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 13 No. 4 • August 2010


If You Have a Heart Attack, Be Sure To Do This While on Your Way to the Hospital

You are probably already familiar with the fact that if you have symptoms of a heart attack, you should chew and swallow a 325 mg aspirin (this is a full size aspirin, not the low dose kind) to interfere with ongoing platelet aggregation and increase your chances of both surviving and of preserving more of your myocytes (heart cells). A new paper1 reports a simple and very cheap new technique for improving the outcome if you have a heart attack.

A newly reported study1 tested the hypothesis that remote ischemic conditioning (induced by repeated brief periods of limb ischemia—reductions in and then restoration of blood flow) after the onset of a heart attack but before reperfusion, reduces the size of the infarct (killed heart tissue). This technique had already been shown to reduce infarct size in a pig heart attack model. The remote ischemic conditioning was applied during the ride in the ambulance and consisted of four cycles of 5 minute inflation and 5 minute deflation of a blood-pressure cuff around the arm.

The researchers report on a group of 333 consecutive adult patients with a suspected first acute heart attack who received this remote ischemic conditioning treatment (82 were excluded on arrival at the hospital because they did not meet inclusion criteria, while another 77 did not complete followup, leaving 174 patients in the analysis of results). The median salvage index (calculated as the difference between area at risk and final infarct size as a percentage of the left ventricular mass volume) was 0.75 in the remote conditioning group versus 0.55 in the control group. The authors conclude: “Remote ischaemic conditioning before hospital admission increases myocardial salvage and has a favourable safety profile.”

A question unanswered by this study is whether chewing and swallowing an aspirin along with remote ischemic conditioning would have greater (additive or synergistic) beneficial effects over an aspirin alone or (though we consider it unlikely) a lower amount of protection than an aspirin alone. Only new research will answer this question.

In the meantime, the hell with Medicare. Paramedics are not likely to charge you much (we certainly hope!) to pump up and release a blood pressure cuff for four cycles of 5 minutes of inflation and 5 minutes of deflation. If it was us, we’d do it to ourselves but we can make NO recommendation concerning anyone else—we mean it. Show your doctor the paper and discuss it with him/her.

How Remote Ischemic Conditioning Works

There was a short review in the July 2010 Nature Medicine2 on the current understanding of how remote conditioning works. The author cites a 1986 study3 of induced heart attacks in dogs that introduced the term and the concept of “ischemic conditioning.” The researchers used the technique of four intermittent periods of occlusion and reperfusion for five minutes—accomplished in this case by constricting and then releasing a coronary artery with a silk suture. The result was a reduction in the size of myocardial infarction. Since then it has been found that the brief episodes of ischemia-reperfusion that comprises the conditioning doesn’t even have to be performed in the myocardium, but can provide heart protection even when done in a tissue far from the heart such as the lower limb muscle, as was shown in a rabbit study.4 In another study cited in the Nature Medicine review,2 remote conditioning administered to patients undergoing coronary stenting (the insertion of a device to hold open a blood vessel) experienced lower procedure-related ischemic chest discomfort, cardiac troponin I release, and subsequent cardiovascular events.5

The actual mechanisms that are responsible for the protective effects of remote conditioning are still in early stages of investigation. The author2 of the review notes that autocoids, biological factors locally released from the preconditioned tissue, which includes bradykinin, adenosine, or opioids, are hypothesized to be involved. In percutaneous interventions such as angioplasty, it has been found that cardioprotection is enhanced by combining conditioning with the opioid morphine, as was shown in one study6 cited in the review where the combination of conditioning and morphine was monitored by ST-segment deviation resolution and lower-peak troponin I levels. Moreover, “exogenous activation of delta- and kappa-opioid receptors confers protection against myocardial stunning in mouse heart, such as improved recovery from contractile dysfunction after ischemia.”2 The review continues with further discussion of possible effects of various opioid receptors on chemokines involved in inflammatory reactions that might be involved in ischemia-reperfusion injury.

Clearly the mechanistic basis for remote conditioning is not very well understood, but it is something that ought to be thoroughly investigated as it could potentially save large numbers of lives. It is a technique that (based on the available data) might be safe and beneficial, though the author2 of the review cautions that “[a]lthough this noninvasive and inexpensive intervention is simple and safe to apply and was even beneficial in patients with an occluded coronary artery, large-scale trials are necessary to confirm these results.” Though nobody is going to make any money investing in clinical research on blood pressure cuffs, the good news is that this sort of large clinical trial would be much less expensive and produce results much more quickly than drug studies. Hence, it is likely that there will eventually be a large trial funded by grants from government, foundations, or cardiovascular disease charities (such as the American Heart Association).

References

  1. Betker 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. The Lancet 375:727-4 (2010).
  2. Weber. Bedside to bench: Receptor cross-talk in remote conditioning. Nature Medicine 16(7):760-2 (2010).
  3. Murry et al. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124-36 (1986).
  4. Birnbaum et al. Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit. Circulation 96:1641-6 (1997).
  5. Hoole et al. Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial. Circulation 119:820-7 (2009).
  6. Rentoukas et al. Cardioprotective role of remote ischemic periconditioning in primary percutaneous coronary intervention: enhancement by opioid action. JACC Cardiovasc Interv 3:49-55 (2010).

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