CARDIOVASCULAR PROFILE OF RO-40-5967, A NEW NONDIHYDROPYRIDINE CALCIUM-ANTAGONIST, DELINEATED IN ISOLATED, BLOOD-PERFUSED DOG HEARTS

Coronary and cardiac effects of Ro 40-5967 were compared in isolated, blood-perfused dog heart preparations. Intraarterial Ro 40-5967 increa sed blood flow in all preparations. In sinoatrial preparations, Ro 40- 5967 decreased sinus rate and produced atrial stand-still when adminis tered at high doses. In paced atrioventricular (AV) node preparations, Ro 40-5967 injected into the posterior septal artery (which perfuses the AV node) increased AV conduction time and at high doses produced s econd- or third-degree AV block. In the same preparations, Ro 40-5967 had little effect on AV conduction time, even at higher doses, when in jected into the anterior septal artery (which perfuses the His-Purkinj e ventricular system). In paced papillary muscle preparations, Ro 40-5 967 reduced the force of contraction only at high doses. In spontaneou sly beating papillary muscle preparations, Ro 40-5967 decreased the fo rce of contraction only at high doses and had no effect on the rate of automaticity even at higher doses. The dose that doubled blood flow w as about one-fifth of the dose that produced a 15% decrease in sinus r ate and also one-fifth of the dose that produced a 15% increase in AV conduction time. The dose that reduced the force of contraction by hal f was >10 times the dose that doubled blood flow. The results indicate that the cardiovascular profile of Ro 40-5967 differs from those of v erapamil and diltiazem but instead resembles that of dihydropyridine d erivatives, which are classified as vasoselective calcium antagonists.