THE INFLUENCE OF NITROGLYCERIN AND DIPYRIDAMOLE ON PACING-INDUCED S.T SEGMENT DEPRESSION IN UNANESTHETIZED, ATHEROSCLEROTIC RABBITS

¹ Department of Pharmacology, Squibb Institute for Medical Research, Princeton, New Jersey

The present studies were undertaken to determine if the antianginal effects of nitroglyccrine could be demonstrated in the atherosclerotic rabbit. Male New Zealand White rabbits were obtained at three months of age and placed an a diet containing 2% cholesterol. After one to four months, a polyvinyl catheter was implanted into the precava under local anesthesia, for subsequent insertion of a bipolar pacing electrode into the right atrium. During experiments, the unanesthetized animals were lightly restrained. Electrocardiographic S-T segment depression was induced by pacing at a rate at least 100 beats/min greater than the intrinsic heart rate. The degree of depression averaged 1 mm at a sensitivity of 1 mV/cm. Reproducible S-T segment changes at a given pacing rate for each animal could be obtained repeatedly on a given experimental day and on subsequent days. Nitroglycerin, administered i.v. (20-100 µg/kg) or via buccal absorption, abolished or significantly attenuated the S-T segment response to pacing in 75% of the animals. Dipynidamole (250 and 500 µg/kg i.v.) was without effect in the same animals. The effectiveness of nitroglycerin in this model clearly differentiates it from dipynidamale, a coronary vasodilator lacking clinical efficacy in angina pectaris.