Abstract 330: No Direct Mitochondrial Protection Against Ischemia Reperfusion Injury in Rat Isolated Hearts by P188 Postconditioning

Abstract

Introduction: Myocardial infarction and cardiac arrest lead to ischemia-reperfusion (IR) injury in the heart. Timely reperfusion through percutaneous coronary intervention and cardiopulmonary resuscitation, respectively, reduces ischemia but also exacerbates myocardial injury. Maintaining mitochondrial function is crucial in maintaining cardiomyocyte function in IR injury. Poloxamer 188 (P188) is a triblock copolymer that has shown protective effects in in-vitro, ex-vivo and in-vivo myocardial IR models. P188 is thought to improve cellular and mitochondrial function during IR by stabilizing membranes. Hypothesis: P188 postconditioning has direct protective effects on mitochondrial function as assessed by ATP synthesis, oxygen consumption and calcium retention capacity (CRC). Methods: After approval by the local authorities, hearts of 42 adult male Sprague-Dawley rats were isolated and perfused ex-vivo with oxygenated Krebs Buffer (KB) for 20 min before 30 min of no-flow ischemia. Hearts were reperfused for 10 min with KB. Cardiac mitochondria were isolated with 1 mM P188 vs 1 mM polyethylene glycol (PEG) vs vehicle by differential centrifugation. Mitochondrial function was assessed for complex I and II substrates of the respiratory chain. Statistics: Kruskal-Wallis with Dunn’s posthoc testing; alpha=0.05. Results: Mitochondrial function decreased significantly after ischemia and showed improvement with reperfusion. P188 did not result in significant improvements in mitochondrial ATP synthesis, oxygen consumption and CRC function after IR, and neither did PEG. Conclusions: P188 does not have a direct protective effect on mitochondria in this model. This might be owed to the fact that no additional damage could be observed after reperfusion which is the type of injury targeted by P188 post-conditioning.