Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST-Segment Elevation Myocardial Infarction.
BACKGROUND
Poloxamer 188 (P188) is a nonionic triblock copolymer believed to prevent cellular injury after ischemia and reperfusion.


OBJECTIVE
This study compared intracoronary infusion of P188 immediately after reperfusion with delayed infusion through a peripheral intravenous catheter in a porcine model of ST segment elevation myocardial infarction (STEMI). Cellular and mitochondrial injury were assessed.


METHODS
STEMI was induced in 55 pigs using 45 minutes of endovascular coronary artery occlusion. Pigs were then randomized to four groups: control, immediate intracoronary (IC) P188, delayed peripheral P188, and polyethylene glycol (PEG) infusion. Heart tissue was collected after 4 hours of reperfusion. Assessment of mitochondrial function or infarct size was performed.


RESULTS
Mitochondrial yield improved significantly with IC P188 treatment compared to control animals (0.25% vs. 0.13%) suggesting improved mitochondrial morphology and survival. Mitochondrial respiration and calcium retention were also significantly improved with immediate IC P188 compared to controls (complex I RCI: 7.4 vs. 3.7 and calcium retention (nmol): 1152 vs. 386). This benefit was only observed with activation of complex I of the mitochondrial respiratory chain suggesting a specific impact of ischemia and reperfusion on this complex. Infarct size and serum troponin I were significantly reduced by immediate IC P188 infusion (infarct size: 13.9% vs. 41.1% and troponin I (μg/L): 19.2 vs. 77.4 μg/L). Delayed P188 and PEG infusion did not provide a significant benefit.


CONCLUSIONS
Intracoronary infusion of P188 immediately upon reperfusion significantly reduces cellular and mitochondrial injury after ischemia and reperfusion in this clinically relevant porcine model of STEMI. The timing and route of delivery were critical to achieve the benefit.
Department of Medicine-Cardiovascular Division, University of Minnesota, Minneapolis, MN.
Jason A
JA
Bartos
Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN.
Timothy R
TR
Matsuura
Department of Medicine-Cardiovascular Division, University of Minnesota, Minneapolis, MN.
Adamantios
A
Tsangaris
Department of Medicine-Cardiovascular Division, University of Minnesota, Minneapolis, MN.
Matthew
M
Olson
Department of Medicine-Cardiovascular Division, University of Minnesota, Minneapolis, MN.
Scott H
SH
McKnite
Department of Medicine-Cardiovascular Division, University of Minnesota, Minneapolis, MN.
Jennifer N
JN
Rees
Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN.
Karen
K
Haman
Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN.
Kadambari Chandra
KC
Shekar
Anesthesiology, TVHS VA Medical Center, Nashville, TN; Departments of Anesthesiology and Pharmacology, Vanderbilt University, Nashville, TN.
Matthias L
ML
Riess
Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN.
Frank S
FS
Bates
Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN.
Joseph M
JM
Metzger
Department of Medicine-Cardiovascular Division, University of Minnesota, Minneapolis, MN.
Demetris
D
Yannopoulos
STEMI; mitochondria; myocardial infarction; poloxamer 188; reperfusion injury
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