Acute Haemodynamic Effects of Felodipine, Verapamil and Hydralazine in the Anaesthetized Dog

Felodipine, a potent dihydropyridine calcium antagonist with a pronounced vascular selectivity, was given intravenously (0.006-0.025 mumol kg-1) to anaesthetized, open-chest dogs with denervated hearts. The result was a dose-dependent decrease in mean arterial pressure (MAP) and total peripheral resistance (TPR), while heart rate (HR), stroke volume (SV) and left ventricular end-diastolic pressure remained relatively unchanged. Cardiac tension work (TTI) and oxygen consumption (MVO2) were reduced, probably due to the decrease in afterload. The relative reduction of the coronary vascular resistance (CVR) was greater than that of TPR. The hypotensive effect of verapamil (0.05-0.20 mumol kg-1) was small and MAP decreased mainly via a decrease in HR and SV. Higher doses of verapamil which induced vasodilatation could not be given without the development of complete atrio-ventricular dissociation. Hydralazine (11-45 mumol kg-1) decreased TPR and CVR in parallel but the decrease in MAP was partly counteracted by a powerful increase in HR, SV and cardiac inotropy which was associated with elevated catecholamine levels in plasma. When MAP and HR were maintained constant by means of aortic balloon inflation and atrial pacing, felodipine markedly increased coronary blood flow and coronary sinus oxygen saturation while SV, TTI, inotropy and MVO2 remained relatively unchanged. It is concluded that felodipine markedly dilates peripheral resistance vessels, and in particular those in the coronary vascular bed, without any cardiodepressant effects.