Comparative effects of bepridil, diltiazem, nifedipine and verapamil on haemodynamic parameters and myocardial oxygen consumption in anaesthetized dogs
Beaughard, M.; Michelin, M.T.; Tisne-Versailles, J.; Lamar, J.C.
Archives Internationales de Pharmacodynamie et de Therapie 284(2): 276-296
ISSN/ISBN: 0003-9780 PMID: 3493742 Accession: 004993833
The haemodynamic effects of 4 calcium antagonists, bepridil (1.25 to 5 mg/kg i.v.), diltiazem (0.1 to 0.3 mg/kg i.v.), nifedipine (0.01 to 0.03 mg/kg i.v.) and verapamil (0.1 to 0.3 mg/kg i.v.) were compared in anaesthetized open-chest dogs. The following parameters were measured: sinusal coronary blood flow (SCBF), total coronary vascular resistance (TCVR), aortic blood pressure, heart rate, left dP/dt max, amplitude of right ventricular contraction, double product, myocardial oxygen consumption (MVO2) and arterial and coronary venous blood gases (pO2 and pCO2) and pH. All 4 substances increased SCBF and decreased TCVR. The greatest effects, taking into account relative dose size, were obtained with nifedipine and verapamil. These 2 substances also had the greatest effect on systemic vasodilatation, as reflected by hypotension. The 4 substances had a direct negative chronotropic effect on the myocardium, an effect which was masked by reflex sympathetic stimulation and decreased vagal tone secondary to a drop in blood pressure. The most marked negative chronotropic effects were seen with diltiazem, verapamil and bepridil in that order. Nifedipine and verapamil produced the greatest negative inotropic effects, whereas diltiazem had very little effect on this parameter. The direct consequence of these haemodynamic effects of the 4 substances was to improve oxygenation of the myocardium. The most durable effect on PvO2 was seen with nifedipine and verapamil. The findings demonstrate not only the heterogeneous action of the 4 calcium antagonists, but also the influence of the experimental conditions on the effects obtained with these substances.