Ibuprofen-mediated infarct size reduction: Effects on regional myocardial function in canine myocardial infarction

Abstract

Normal, marginal, and central ischemic regional myocardial function were evaluated in a canine model of myocardial infarction during 90 minute left circumflex coronary artery occlusion in 25 anesthetized dogs randomly assigned to intravenous ibuprofen infusion ( n = 13, 5.36 mg/kg/h beginning 1 hour before occlusion) or vehicle solution as control ( n = 12) and in 15 conscious, unsedated dogs 48 and 72 hours after 90 minute circumflex artery occlusion followed by reperfusion (ibuprofen, 5.36 mg/kg/h by intravenous infusion over 7 hours beginning 1 hour before occlusion, n = 7; or vehicle solution infusion as control, n = 8). Miniature subendocardial sonomicrometer crystal pairs were used to calculate left ventricular regional end-diastolic segment length, end-systolic segment length, and regional percent systolic shortening. Infarct size was estimated in 72 hour animals by a postmortem dual perfusion technique using triphenyltetrazolium histochemical dye and Evan's blue dye for determination of infarct area, risk area, and area not at risk. Ibuprofen treatment significantly reduced infarct size expressed as percent of risk area (mean ± standard deviation of 44.6 ± 18 versus 64.4 ± 16% for control dogs, p < 0.05) but it did not improve normal, marginal, or ischemic region end-diastolic length, end-systolic length or percent systolic shortening during coronary occlusion in anesthetized dogs or after reperfusion in conscious animals at 48 and 72 hours, and it did not enhance inotropic reserve at 72 hours in conscious animals. During 90 minute circumflex occlusion in anesthetized dogs, ibuprofen was associated with increases in systemic arterial pressure and worsened ischemic regional percent systolic shortening. Thus, ibuprofen does not improve normal, marginal, or ischemic zone regional myocardial function during acute ischemia or 48 or 72 hours after myocardial reperfusion despite a significant reduction of infarct size.