Preconditioning with Ischemia: A Means to Delay Cell Death in Ischemic Myocardium
We have previously shown that a brief episode of ischemia slows the rate of ATP depletion during subsequent ischemic episodes (1). Additionally, intermittent reperfusion washes out ischemic catabolites which may be harmful to the myocardium. Thus, we proposed that brief, repetitive episodes of ischemia might actually protect the heart from a subsequent sustained ischemic insult. To test this hypothesis, two sets of experiments were performed. In the first set, dogs were “preconditioned” with four 5 minute circumflex occlusions, each separated by 5 minutes of reperfusion, following which they received a sustained 40 minute occlusion. The control group received a single 40 minute occlusion. In the second study animals were preconditioned in an identical manner, following which they received a sustained 3 hour occlusion. Control animals received a single 3 hour occlusion. All animals were allowed 4 days of reperfusion to permit histologic infarct sizing. Infarct size was then related to baseline predictors of infarct size, namely the size of the area at risk and collateral blood flow. In the 40 minute study, preconditioning paradoxically limited infarct size to 25% of that seen in control animals (p<.001). Collateral blood flow (microspheres) was not significantly different between the groups. In the 3 hour study, preconditioning had no effect on infarct size. The protective effect in the 40 minute study may have been due to reduced ATP depletion and/or reduced catabolite accumulation during the sustained occlusion. These results suggest that multiple anginal episodes, which often precede myocardial infarction in man, may delay cell death after coronary occlusion, and thereby allow for greater salvage of myocardium by reperfusion therapy.
KeywordsMyocardial Blood Flow Collateral Flow Coronary Occlusion Ischemic Episode Collateral Blood Flow
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