6-methyl-1-2-3-5-tetrahydroimidazo(2-1-b)quinazolin-2-one-hydrochloride and Disease-Models--Animal

Topics: Animals; Blood Platelets; Carrier Proteins; Collagen; Coronary Vessels; Dipyridamole; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Drug Therapy, Combination; Extracellular Matrix Proteins; Glycoproteins; Ligation; Myocardial Infarction; Platelet Aggregation; Quinazolines; Sulfinpyrazone

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.

Topics: Animals; Aspirin; Blood Pressure; Disease Models, Animal; Dogs; Epinephrine; Female; Imidazoles; Male; Myocardial Infarction; Necrosis; Phenoxybenzamine; Platelet Aggregation; Propranolol; Quinazolines