Poloxamer 188 is a
surfactant with hemorheological, antithrombotic, and neutrophil-inhibitory properties. This agent has been demonstrated to reduce
infarct size and to improve left ventricular function in animal models of
myocardial infarction and reperfusion, and recently in a randomized trial of patients receiving
thrombolytic therapy for acute
myocardial infarction. In addition to reducing
reperfusion injury,
poloxamer 188 might be beneficial by increasing collateral blood flow. The purpose of this study was to determine the effect of
poloxamer 188 on collateral blood flow,
myocardial infarct size, and left ventricular function in a canine model of prolonged (3 hours)
coronary occlusion and reperfusion. Closed-chest dogs (n = 21) underwent a 3-hour
coronary occlusion and 3 hours of reperfusion. At 1 hour of occlusion, dogs received
poloxamer 188, 75 mg/kg IV bolus, followed by 150 mg/kg/h IV for the final 2 hours of
coronary occlusion and throughout reperfusion, or a saline placebo. Regional myocardial blood flow was measured using colored
microspheres.
Myocardial infarct size and area at risk were determined by postmortem histochemical staining. Compared with controls,
poloxamer 188-treated dogs showed no significant increase in collateral blood flow during the final 2 hours of a 3-hour coronary artery occlusion. In addition,
poloxamer 188 treatment had no beneficial effect on
infarct size or left ventricular function in this model. Increased collateral blood flow is unlikely to be a beneficial mechanism of
poloxamer 188 in
myocardial infarction. These data also question the benefit of this agent to reduce
reperfusion injury in the setting of more prolonged (3-hour)
coronary occlusion.