sq-30741 and Reperfusion-Injury

The ischemia-reperfusion lung injury is characterized by increased pulmonary vascular resistance, edema, and subsequent deterioration of oxygenation. Other models of acute lung injury suggest that thromboxane A2 may contribute to the pulmonary hypertension after transplantation.. We studied the effects of the selective thromboxane A2 receptor antagonist SQ 30741 on pulmonary hemodynamics and gas exchange in porcine single lung transplantation using extracorporeal circulation (right heart bypass) with separate cannulations of the right and left pulmonary arteries. Pulmonary vascular resistance was measured at equal and constant flow to each lung. Flow distribution between the lungs was registered at equal pulmonary artery pressures. Twelve pigs (weight 17 to 23 kg) were studied. At the onset of reperfusion a bolus dose of the drug (5 mg/kg) was injected into both pulmonary arteries followed by an infusion (5 mg/kg/hr) for 1 hour (SQ group, n = 6). The control group (n = 6) received an equal amount of vehicle. The systemic and pulmonary hemodynamics and blood gas values were registered during 2 hours of reperfusion.. The pulmonary vascular resistance of the transplanted lung was significantly higher compared with the native lung (p < 0.001). Administration of SQ 30741 failed to ameliorate the pulmonary pressor response of the graft in comparison with the control group. No difference was found in the systemic arterial oxygen tension between the two groups.. Thromboxane does not seem to be among the principal mediators in the pulmonary hypertension after transplantation.

Topics: Animals; Hypertension, Pulmonary; Lung Transplantation; Pulmonary Circulation; Pulmonary Gas Exchange; Receptors, Thromboxane; Reperfusion Injury; Swine; Thromboxane A2

We determined if the thromboxane A2 antagonist SQ 30,741 can reduce ultimate myocardial infarct size and reperfusion injury. Anesthetized dogs were subjected to left circumflex coronary artery occlusion for 90 min at which time reperfusion was instituted. In one study, SQ 30,741 (1 mg/kg + 1 mg/kg/hr) was given either 10 min postocclusion (n = 7) or 2 min (n = 9) before reperfusion along with their appropriate vehicle controls in a model of 90 min of occlusion and 5 hr of reperfusion. Infarct size was reduced 50% (P less than .05) when SQ 30,741 was given 10 min postocclusion and 30% (P less than .05) when given only during reperfusion. Flow reserve using maximally dilating doses of adenosine was determined 3 hr postreperfusion in vehicle (10 min postocclusion, n = 10), SQ 30,741 (10 min postocclusion, n = 6) and nonischemic (n = 5) animals. Maximal subendocardial flow was reduced during reperfusion in ischemic animals, but SQ 30,741 improved this compared to vehicle animals (400 +/- 95, 88 +/- 25 and 208 +/- 48 ml/min/100 g; nonischemic, vehicle, SQ 30,741 groups, respectively). To determine if myocardial salvage can be observed 24 hr postocclusion with SQ 30,741 or the cyclooxygenase inhibitor aspirin, dogs were given vehicle (n = 9), SQ 30,741 (10 min postocclusion up to 4 hr postreperfusion) or aspirin (n = 9, 40 mg/kg 30 min preocclusion) and infarct size was determined 24 hr postocclusion (90 min left circumflex coronary artery occlusion + reperfusion).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine; Animals; Aspirin; Coronary Circulation; Dogs; Female; Male; Myocardial Infarction; Receptors, Prostaglandin; Receptors, Thromboxane; Reperfusion Injury; Thromboxane A2