Effect of BW755C in an occlusion-reperfusion model of ischemic myocardial injury

Abstract

BW755C is a new antiinflammatory agent which predominantly inhibits lipoxygenase over cyclooxygenase. Effects of BW755C have been examined in a canine, occlusion-reperfusion, model of ischemic myocardial injury. In pentobarbital anesthetized open-chest dogs, the proximal left circumflex coronary artery (LCX) was occluded for 90 minutes and slowly reperfused using a micrometer-driven occluder. Thirty minutes before occlusion, animals randomly received BW755C, 3 mg/kg (n = 7), or 10 mg/kg (n = 8), or saline (n = 16) by intravenous infusion. The thoracotomy was closed and the animals subsequently were killed at 24 hours. Infarct size and anatomic area dependent on the occluded LCX were determined by a dual staining technique using triphenyltetrazolium and Evan's blue. Both doses of BW755C significantly reduced the ultimate extent of irreversible myocardial ischemic injury, whether results were expressed as grams of infarcted tissue or as percent of risk region infarcted. No difference in risk region size was observed between groups. No effects of BW755C on heart rate, arterial pressure, or left circumflex flow were observed. BW755C (10 mg/kg) did not significantly inhibit ex vivo platelet aggregation in response to collagen, adenosine diphosphate, or arachidonic acid. These results suggest that inhibition of lipoxygenase may reduce the extent of ischemic damage to the heart.