Abstract 333: Poloxamer 188 Prevents the Impairment in Mitochondrial Respiration Induced by ST-Segment Elevation Myocardial Infarction
Introduction: Poloxamer 188 (P188) is a nonionic copolymer shown to protect neurons, skeletal muscle, and potentially cardiac muscle from ischemia/reperfusion injury. P188 is proposed to seal stress-induced gaps in cell membranes, but its mechanism remains unproven. We hypothesized that P188 would improve mitochondrial function after ischemia and reperfusion in a porcine model of ST segment Elevation Myocardial Infarction (STEMI).
Methods: Occlusion of the second obtuse marginal artery was performed in 12 pigs using an intracoronary balloon catheter. Animals were randomized to P188 or Control. After 45 minutes of ischemia, the balloon was removed. The P188 group received an intra-coronary bolus of P188 (250 mg/kg) into the left main coronary artery followed by a continuous intravenous P188 infusion (500 mg/kg) over 4 hours. Controls received equivalent volumes of normal saline. After 4 hours of reperfusion, heart tissue was harvested from the infarct zone and the non-ischemic anterior wall. Mitochondria were isolated. Respiration was measured in the presence of complex I (pyruvate+malate) or complex II (succinate+rotenone) substrates. Respiratory Control Index (RCI) was calculated as the ratio of stage 3 to stage 4 respiration. The ratio of RCIs from the infarct area to the non-ischemic anterior wall was calculated for each animal.
Results: In Controls, RCI was significantly reduced in the infarct zone compared to the anterior wall for both complex I and II [3.2 ± 1.3 vs. 9.7 ± 4.8 (p=0.01) and 1.9 ± 0.8 vs. 3.5 ± 0.34 (p=0.002), respectively]. P188 mitigated the reduction in complex I RCI in the infarct zone compared to controls (7.0 ± 3.3 vs. 3.2 ± 1.3, p=0.03) while it had no effect on the reduction in complex II RCI (2.3 ± 1.1 vs. 1.9 ± 0.8, p=0.53). The infarct/anterior wall RCI ratio for complex I was significantly improved with P188 treatment compared to Controls (0.96 ± 0.43 vs. 0.38 ± 0.22, p=0.02). There was no significant difference between P188 and Control animals for complex II (0.68 ± 0.32 vs. 0.55 ± 0.21, p=0.43).
Conclusions: P188 treatment, given immediately at the time of revascularization during an acute myocardial infarction, protects complex I respiration but does not appear to affect complex II. The detailed mechanism must be investigated further.
Author Disclosures: J.A. Bartos: None. T.R. Matsuura: None. G. Debaty: None. S.H. McKnite: None. J.N. Rees: None. F. Bates: None. J.M. Metzger: None. D. Yannopoulos: None.
- © 2014 by American Heart Association, Inc.