Abstract 8: Remote Ischemic Preconditioning Mitigates Myocardial and Neurological Dysfunction via KATP Channel Activation in a Rat Model of Hemorrhagic Shock

Abstract

Introduction: We investigated whether remote ischemic pre-conditioning (RIPC) would reduce myocardial and cerebral ischemia and reperfusion injuries during and following hemorrhagic shock. Hypothesis: RIPC mitigates myocardial and neurological dysfunction as the result of K ATP channel activation. Methods: Twenty-one male Sprague Dawley rats were randomized into three groups:1) RIPC; 2) RIPC with K ATP channel blocker (RIPC+blocker); 3) Control. RIPC was induced by four cycles of 5 mins of limb ischemia followed by reperfusion for 5 mins. Hemorrhagic shock was induced by removing 50% of the estimated total blood volume over an interval of 1 hour, 30 mins after bleeding, the animals were reinfused with shed blood during the ensuing 30 mins. All animals were monitored and observed for an additional 72 hours. Myocardial function was measured by echocardiography at baseline, 1 hour after bleeding, 30 mins after shock, 30 mins after reinfusion and at hourly intervals after reinfusion. The survival and neurological function were evaluated daily for a total of 72 hours. Results: At 2 hours after reinfusion, ejection fraction was restored to near-baseline levels and was significantly better than the Control group. Myocardial performance index was significantly decreased than the Control group. In addition, all animals survived for 72 hours in the RIPC group. The duration of survival was significantly longer than the Control group. Neurological deficit score was significantly better in the RIPC group than the control animals. However, pre-treatment of the K ATP channel blocker completely abolished the myocardial and cerebral protection effects of RIPC (Table). Conclusions: In a rat model of severe hemorrhagic shock, RIPC mitigated myocardial and neurological dysfunction with improved survival by activation of the K ATP channel.