Abstract 17476: Poloxamer 188 Prevents Mitochondrial Impairment Induced by ST Segment Elevation Myocardial Infarction in a Time and Route-dependent Manner

Abstract

Introduction: Poloxamer 188 (P188) is a nonionic copolymer known to prevent ischemia-reperfusion injury in cardiac tissue. The mechanism is unknown, though it is believed to prevent unregulated ion flux by sealing stress-induced gaps in sarcolemmal membranes. We hypothesized that immediate intra-coronary P188 infusion would prevent mitochondrial impairment after ischemia/reperfusion in a porcine model of ST segment elevation myocardial infarction (STEMI). Methods: STEMI was induced in 55 pigs by 45 minutes of endovascular coronary occlusion. Upon reperfusion, animals were randomized to four groups: control, immediate intra-coronary P188 treatment (I-P188), delayed P188 treatment (D-P188) initiated after 30 minutes of reperfusion through a peripheral intravenous catheter, or immediate intra-coronary infusion of polyethylene glycol (PEG). Mitochondria were harvested from non-ischemic and ischemic heart tissue after 4 hours of reperfusion. Mitochondrial respiration (RCI) and calcium retention capacity (CRC) were measured in the presence of complex I or complex II substrates. Infarct size was measured after 4 hours of reperfusion by TTC and Evans Blue staining. Results: Mitochondrial yield significantly improved with I-P188 treatment suggesting normalization of mitochondrial morphology whereas all other groups were similarly reduced. In control, D-P188, and PEG groups, the RCI was significantly reduced in ischemic compared to non-ischemic tissue for complex I and complex II. I-P188 treatment prevented the reduction in complex I RCI while it had no effect on reduction of complex II RCI. The CRC also increased in ischemic mitochondria from animals treated with I-P188 compared to all other groups. Infarct size was reduced by 66% or more with I-P188 treatment compared to the other groups. Serum troponin was similarly reduced only in the I-P188 treatment group. Conclusions: Immediate intra-coronary P188 treatment prevents mitochondrial damage and reduces infarct size after STEMI. This benefit is not observed when treatment is delayed and delivered through a peripheral IV. While the mechanism remains unknown, the amphipathic properties of P188 are necessary as PEG infusion did not provide a significant benefit.