Thromboxane A 2 receptor blockade improves contractile function following cardiopulmonary bypass in dogs and pigs

Abstract

Thromboxane A 2/prostaglandin endoperoxide (TP) receptor antagonists have been reported to decrease the extent of myocardial damage after coronary ligation. The purpose of this study was to determine if the TP antagonist SQ 30,741 can protect myocardial tissue during cardiac arrest and cardiopulmonary bypass (CPB) in dogs and pigs. In the first part of the study, anesthetized dogs were subjected to normothermic CPB (37.5°C) at a flow rate of 2 liters/m 2/min. Dogs were treated with either 5 mg/kg + 5 mg/kg/hr SQ 30,741 or vehicle starting before CPB. The aorta was cross-clamped for 25 min and then released to allow reperfusion. In another study, pigs had hypothermic (28°C) CPB but with arrest for 1 hr. Myocardial recovery was assessed by segment shortening as determined by sonomicrometry. Canine hearts treated with SQ 30,741 had a significantly improved reperfusion contractile function such that at 60 min postreperfusion, segmental shortening returned to 96% of pre-bypass levels vs 70% in vehicle-treated controls ( P < 0.05). In pigs, 70% of vehicle-treated pigs could not be weaned off CPB and died. All six pigs treated with SQ 30,741 survived. SQ 30,741 prevented platelet loss in dogs, but did not in pigs. Thus, SQ 30,741 significantly improved reperfusion function in hearts subjected to CPB.