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Diltiazem is a potent coronary vasodilator which is assumed to act directly on vascular smooth muscle (1, 2). A relaxing effect is produced on isolated smooth muscles in both normal and potassium depolarized solutions. The compound antagonizes non-competi tively the contractions induced by various spasmogens in the isolated ileum (3). In the rabbit ear artery perfused with potassium depolarizing solution, diltiazern antagonized calcium ions: the dose-response curves for the relation between vasoconstriction and CaCl2 were shifted by diltiazern to the right without depressing the maximum response (4). In the present study, the antagonism between diltiazem and calcium ions was examined in the coronary vascular bed of the perfused guinea pig heart and in the isolated canine coronary artery.Langendorff's method was used for testing the effect of diltiazem on the coronary flow in guinea pig heart. The isolated heart was perfused at a constant pressure with Locke Ringer solution (NaCI 154, KCI 5.6, CaC12 2.2, MgCI2 2.1, NaHCO3 5.9, glucose 2.8 mM, equilibrated with 95 % 02 and 5 % C02). To eliminate spontaneous movement of the heart, a fibrillated heart was prepared by applying AC current (50 Hz, 10 V) to the right auricle (2). The outflow of the perfusate was measured by means of a drop counter and experi ments were carried out at 30°C. The drug solution (0.1 ml) was injected into the aortic cannula and dose response curves for diltiazem were obtained 15 min after perfusion with

Abstract-Cardiovascular

Abstract-We studied the arrhythmogenic activity of denopamine, in relation to its positive inotropic action, in dogs and compared it with those of catecholamines. The positive inotropic activities of the compounds as expressed in terms of the ED, 00 (itg/kg, i.v.), that increased LV dp/dt max of anesthetized dogs by 100% of the control were 8.0 for denopamine, 0.27 for norepinephrine, 0.03 for isoproterenol, 3.8 for dobutamine and 16 for dopamine.On the other hand, the doses of these drugs at which the "non-sinus/total rate" increased significantly (about 30% of total beats, ,ug/kg, i.v.) were more than 1000 for denopamine, 1.0 for norepinephrine and isoproterenol, and 300 for dobutamine and dopamine in coronary ligated dogs.