Abstract
Myocardial infarction can experimentally be produced in cholesterol-fed rabbits by flushing of thromboxane A2 (TXA2) into the aortic root. Using this model, we studied the preventive effects of the anti-platelet agents such as aspirin, phthalazinol-a cyclic AMP phosphodiesterase inhibitor and ticlopidine-adenylate cyclase activator.
Eighteen male albino rabbits were fed with one percent cholesterol containing pellets for 20 weeks and then with a commercial diet for 5 weeks. Fourteen rabbits were handled as the treated groups. Four rabbits were given 10mg/kg of aspirin orally every morning for seven days before the experiment. In the same way, six rabbits were treated with 400mg/kg of phthalazinol and four rabbits with 200mg/kg of ticlopidine. Other four rabbits were treated for the same period with placebo capsules of potato starch as placebo controls. Twenty-five μg of prostaglandin H2 and 2.5mg protein of microsome obtained from cow platelets were mixed and flushed into the coronary circulation through an indwelling balloon catheter, which was 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 prominently immediately after flushing of TXA2. Parallel to these changes, 6-keto PGF1α levels were also high immediately after flushing but former levels were reverted to 5 minutes after injection. Histological and histochemical studies, 48 hours after flushing, revealed an ischemic areas of various size, scattered irregularly from the endocardial to epicardial lesions of the ventricles. Microthrombi, what we call “shower thrombi”, were observed in many intramuscular small coronary vessels.
On the other hand in the treated groups, Q waves were recorded in only one of four in the aspirin, only two of six in the phthalazinol and none of four in the ticlopidine treated rabbits. Plasma levels of TXB2 of these three treatedgroups increased immediately after flushing, but their maximal values were lower than those in control group during the experimental period. Histological studies demonstrated that ischemic lesions were smaller and less frequently encountered in the three treated-group rabbits.
Plasma levels of cAMP and cGMP arose at the maximum interestingly five minutes after flushing in the three groups except the aspirin, although the levels of prostanoid did the maximum just immediately after flushing.
These data demonstrate that thromboxaneinduced myocardial infarction could be prevented by the treatment with the anti-platelet agents such as aspirin, phthalazinol, ticlopidine-treated rabbits.
