Preventive Effect of Phthalazinol against Thromboxane Induced Myocardial Infarction in Cholesterol-fed Rabbits

Phthalazinol, a cyclic AMP phosphodiesterase inhibitor has an antiplatelet aggregating effect. The preventive effect of this agent against thromboxaneinduced myocardial infarction was studied.Twelve male albino rabbits were fed one percent cholesterol containing pellets for 20 weeks and then a commercial diet for 5 weeks. Six rabbits were given 400mg/kg of phthalazinol orally every morning for 1 week before the experiment. Others were treated for the same period with potato starch as placebo controls. Twenty-five μg of prostaglandin H2 and 2.5mg protein of microsome obtained from cow platelets were injected into the coronary circulation through an indwelling balloon catheter inserted through carotid artery into the aorta to the levels of the orifice of the aortic valve. ECG, BP, plasma levels of thromboxane B2 (TXB2), 6-keto prostaglandin F1α (6-keto PGF1α), cyclic AMP (cAMP), cyclic GMP (cGMP), GOT, GPT, LDH and CPK were monitored for 48 hours.In the placebo control rabbits, all rabbits exhibited typical ST elevation in II, III aVF and/or precordial leads immediately after injection of TXA2 and Q waves followed. Plasma levels of TXB2 increased statistically and significantly and remained high for 10 minutes after flushing. Parallel to these changes, 6-keto PGF1α levels were also high immediately after flushing but the former levels were reverted to 3 minutes after injection. Histological and histochemical studies, 48 hours after flushing revealed an ischemic area scattered irregularly from the endocardial to epicardial lesions of the ventricles. Microthrombi were present in the small coronary vessels.In the phthalazinol treated rabbits, Q waves were recorded in only two. Plasma levels of TXB2, which increased immediately after flushing, were statistically significantly low as compared with those in control group. Histological studies revealed that ischemic lesions were smaller and less frequently encountered in the wall of the ventricle of phthalazinol treated rabbits.Thromboxane-induced myocardial infarction was to some extent prevented in phthalazinol treated rabbits.