The effect of a potent inhibitor of platelet aggregation, BL-3459, on adrenaline-induced myocardial necrosis in beagle dogs.
The effect of a potent inhibitor of platelet aggregation, BL-3459, on adrenaline-induced myocardial necrosis was investigated in beagle dogs. BL-3459, an alpha-adrenergic receptor blocking agent, phenoxybenzamine, and a beta-adrenergic receptor blocking agent, propranolol, were compared for their ability to modify the effects of adrenaline on platelet function, arterial blood pressure and myocardial damage. Adrenaline infusion led to a dose-related myocardial damage, elevation in arterial blood pressure, elevation in screen filtration pressure (SFP) and fall in platelet count. BL-3459 inhibited the elevation in SFP and the fall in platelet count as well as limiting the extent of myocardial damage. Phenoxybenzamine significantly modified all adrenaline-induced changes except the elevation in SFP. Propranolol had little effect alone and seemed to antagonize the beneficial effects of BL-3459 when the two drugs were combined. These results suggest that while other factors may also be involved, platelet aggregation and transient hypertension are correlated with the extent of adrenaline-induced myocardial necrosis observed in this model. A potent inhibitor of platelet aggregation, BL-3459, and the alpha-adrenergic receptor blocking agent, phenoxybenzamine, appear to afford protection against the observed pathological effects.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004837:Epinephrine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced*; D009336:Necrosis; D010643:Phenoxybenzamine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*
D007093:Imidazoles; D011799:Quinazolines; D010643:Phenoxybenzamine; C009709:6-methyl-1,2,3,5-tetrahydroimidazo(2,1-b)quinazolin-2-one hydrochloride; D011433:Propranolol; D001241:Aspirin; D004837:Epinephrine