Reduction in Reperfusion-Induced Myocardial Necrosis in Dogs by RheothRx Injection

Background Reperfusion after prolonged coronary artery occlusion may be followed by additional myocardial necrosis persisting for hours to days. Potential mechanisms include neutrophil-mediated injury and compromised flow within the microcirculation of the reperfused myocardium. Poloxamer 188 is a nonionic surfactant with beneficial hemorheological and neutrophil-inhibitory properties. The purpose of the present study was to determine if poloxamer 188 is capable of reducing the myocardial injury associated with sustained reperfusion and to examine the effect of treatment duration. Methods and Results Three groups of closed-chest dogs underwent 90 minutes of left anterior descending coronary artery occlusion (angioplasty balloon) and 72 hours of reperfusion. Poloxamer 188, formulated as RheothRx Injection (Burroughs Wellcome Co), was given as a 75 mg/kg IV bolus 15 minutes before reperfusion followed by a 150 mg kg`1 h1 continuous IV infusion for 4 hours (n= 13) or 48 hours (n= 13); control dogs (n= 12) received saline for 48 hours. The 48-hour infusion of poloxamer 188 resulted in a 42% reduction in infarct size (as a percent of the area at risk) compared with the control group (25.0±4.2% versus 43.3±4.3%, P<.01), whereas the 4-hour group demonstrated a 25% reduction in infarct size compared with the control group (32.4±4.3%, P=.08). ANCOVA demonstrated that the 48-hour infusion of poloxamer