Effect of the thromboxane A2 receptor antagonist SQ 30,741 on ultimate myocardial infarct size, reperfusion injury and coronary flow reserve.
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)
Grover
G J
GJ
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, New Jersey.
Schumacher
W A
WA
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D017482:Receptors, Thromboxane; D015427:Reperfusion Injury / Q000517:prevention & control*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C054215:SQ 30741; D013928:Thromboxane A2; D000241:Adenosine; D001241:Aspirin