The study investigates the protective effects of brief ischemic episodes (preconditioning) on myocardial injury during subsequent sustained ischemia. In two sets of experiments, dogs were preconditioned with four 5-minute ischemic episodes, each followed by 5 minutes of reperfusion, before undergoing a 40-minute or 3-hour sustained ischemic episode. The results showed that preconditioning significantly reduced infarct size in the 40-minute study, but not in the 3-hour study. In the 40-minute study, preconditioning limited infarct size to 25% of that in the control group, suggesting that it may delay cell death and allow for greater myocardial salvage through reperfusion therapy. The protective effect was not due to increased collateral blood flow, as it was observed in both preconditioned and control groups. The mechanism of preconditioning's protective effect is likely related to reduced ATP depletion or limited catabolite accumulation during the sustained ischemic episode. The findings suggest that the multiple anginal episodes preceding myocardial infarction in humans may have a similar protective effect, potentially allowing for earlier intervention and better outcomes.The study investigates the protective effects of brief ischemic episodes (preconditioning) on myocardial injury during subsequent sustained ischemia. In two sets of experiments, dogs were preconditioned with four 5-minute ischemic episodes, each followed by 5 minutes of reperfusion, before undergoing a 40-minute or 3-hour sustained ischemic episode. The results showed that preconditioning significantly reduced infarct size in the 40-minute study, but not in the 3-hour study. In the 40-minute study, preconditioning limited infarct size to 25% of that in the control group, suggesting that it may delay cell death and allow for greater myocardial salvage through reperfusion therapy. The protective effect was not due to increased collateral blood flow, as it was observed in both preconditioned and control groups. The mechanism of preconditioning's protective effect is likely related to reduced ATP depletion or limited catabolite accumulation during the sustained ischemic episode. The findings suggest that the multiple anginal episodes preceding myocardial infarction in humans may have a similar protective effect, potentially allowing for earlier intervention and better outcomes.