Literature Review: Remote Ischemic Conditioning

      Bøtker HE, Kharbanda R, Schmidt MR, et al. Remote ischemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: A randomized trial. Lancet 375(9,716): 727-34, Feb 2010.

Abstract

   This study tested the hypothesis that remote ischemic conditioning during evolving ST-elevation myocardial infarction, done before primary percutaneous coronary intervention, increases myocardial salvage. Methods—333 consecutive adult patients with suspected first acute myocardial infarctions were randomly assigned in a 1:1 ratio by computerized block randomization to receive primary percutaneous coronary intervention with (n=166) versus without (n=167) remote conditioning (intermittent arm ischemia through four cycles of five-minute inflation and five-minute deflation of a blood-pressure cuff). Patients received remote conditioning during transport and primary percutaneous coronary intervention in hospital. The primary endpoint was myocardial salvage index at 30 days after primary percutaneous coronary intervention, measured by myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment.

   Findings—Median salvage index was 0.75 (IQR 0.50–0.93, n=73) in the remote conditioning group versus 0.55 (0.35–0.88, n=69) in the control group, with a median difference of 0.10 (95% CI, 0.01–0.22; p=0.0333). Mean salvage index was 0.69 (SD 0.27) versus 0.57 (0.26), with a mean difference of 0.12 (95% CI, 0.01–0.21; p=0.0333). Major adverse coronary events were death (n=3 per group), reinfarction (n=1 per group) and heart failure (n=3 per group). Interpretation—Remote ischemic conditioning before hospital admission increases myocardial salvage and has a favorable safety profile. [These] findings merit a larger trial to establish the effect of remote conditioning on clinical outcomes.

Comment

   Many EMS systems now use 12-lead ECGs to rapidly identify patients with STEMIs and transport them to hospitals for immediate angioplasty. However, in most patients, unless there is an extremely short symptom onset-to-reperfusion time, there is still some permanent myocardial damage. Might there be a way to reduce the extent of injury?

   As was first described 25 years ago, researchers have found that temporarily occluding a coronary artery will allow the affected heart muscle to later survive even longer periods of interrupted blood supply—a process called ischemic preconditioning. Further animal research revealed that the myocardium could be protected by creating ischemia in muscle tissue other than the heart: remote ischemic preconditioning. The mechanism for this effect is not known but may involve factors released into the blood or communication via the nervous system.

   This study takes the concept further by testing it on actual STEMI patients. The authors showed that creating temporary ischemia in the arm muscle while a patient's coronary artery was blocked resulted in reduced damage to the myocardium after the artery was reopened.

   More research needs to be done. But if remote ischemic conditioning does improve clinical outcomes, it will be a simple, noninvasive and inexpensive way for EMS systems to improve care for STEMI patients.

   Angelo Salvucci, Jr., MD, FACEP, is medical director for the Santa Barbara County and Ventura County (CA) EMS agencies.