Repeated Remote Ischemic Postconditioning Protects Against Adverse Left Ventricular Remodeling and Improves Survival in a Rat Model of Myocardial Infarction

Abstract

Rationale: Remote ischemic conditioning induced by repeated episodes of transient limb ischemia is a clinically applicable method for protecting the heart against injury at the time of reperfusion. Objective: To assess the effect of chronic, repeated, remote conditioning on infarct size and long-term remodeling after myocardial infarction. Methods and Results: Rats with ischemia/reperfusion injury received different protocols of remote limb conditioning. While a single early episode of remote ischemic conditioning during coronary occlusion (perconditioning) resulted in a decrease in infarct size on both day 4 and day 28, when it was repeated (postconditioning) intermittently (every 3 days) and intensively (every day), it was not associated with a further decrease in infarct size. However, the protection against adverse remodeling offered by a single episode of limb perconditioning was further enhanced by repeated remote postconditioning therapy in a dose-dependent manner. In separate experiments there was a dose-dependent improvement in survival at 84 days by Kaplan–Meier analysis. Conclusions: Whereas a single early episode of remote perconditioning reduces infarct size, repeated remote postconditioning further reduces adverse LV remodeling and improves survival in a dose-dependent fashion. These data may have clinical implications for the treatment of patients with evolving myocardial infarction.