EFFECT OF POLOXAMER-188 ON COLLATERAL BLOOD-FLOW, MYOCARDIAL INFARCT SIZE, AND LEFT-VENTRICULAR FUNCTION IN A CANINE MODEL OF PROLONGED (3-HOUR) CORONARY-OCCLUSION AND REPERFUSION

Poloxamer 188 is a surfactant with hemorheological, antithrombotic, an d neutrophil-inhibitory properties. This agent has been demonstrated t o reduce infarct size and to improve left ventricular function in anim al 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, pol oxamer 188 might be beneficial by increasing collateral. blood flow. T he purpose of this study was to determine the effect of poloxamer 188 on collateral blood flow, myocardial infarct size, and left ventricula r function in a canine model of prolonged (3 hours) coronary occlusion and reperfusion. Closed-chest dogs (n = 21) underwent a. g-hour coron ary occlusion and 3 hours of reperfusion. At 1 hour of occlusion, dogs received poloxamer 188, 75 mg/kg TV bolus, followed by 150 mg/kg/h TV for the final 2 hours of coronary occlusion and throughout reperfusio n, or a saline placebo. Regional myocardial blood flow was measured us ing colored microspheres. Myocardial infarct size and area at risk wer e determined by postmortem histochemical staining. Compared with contr ols, poloxamer 188-treated dogs showed no significant increase in coll ateral blood flow during the final 2 hours of a 3-hour coronary artery occlusion. In addition, poloxamer 188 treatment had no beneficial eff ect on infarct size or left ventricular function in this model. Increa sed collateral blood flow is unlikely to be a beneficial mechanism of poloxamer 188 in myocardial infarction. These data also question the b enefit of this agent to reduce reperfusion injury in the setting of mo re prolonged (3-hour) coronary occlusion.