Negative inotropic properties of isradipine, nifedipine, diltiazem, and verapamil in diseased human myocardial tissue.

We investigated the inotropic responses to Ca2+ antagonists using electrically driven human papillary muscle strips and human auricular trabeculae. Specimens were obtained during cardiac surgery for mitral valve replacement [New York Heart Association (NYHA) Class II-III] or heart transplantation (NYHA IV) and during aortocoronary bypass operations. The inotropic effects were studied with cumulative concentration-response curves. All Ca2+ antagonists tested significantly (p less than 0.05) depressed force of contraction at concentrations above 0.01 mumol/L, but their potencies were different. A 50% reduction of the initial force of contraction occurred at the following concentrations (NYHA II-III): nifedipine (mean IC50) 0.09 mumol/L isradipine 0.12 mumol/L, diltiazem 0.69 mumol/L, and verapamil 0.79 mumol/L. There were no significant differences in the negative inotropic effects of any tested Ca2+ antagonist between NYHA II-III and NYHA IV. When the initial force of contraction was reduced by 90%, addition of Ca2+ increased force of contraction significantly less after diltiazem (2.76 +/- 0.4 mN), isradipine (1.82 +/- 0.23 mN), and nifedipine (1.68 +/- 0.25 mN) compared to control (4.63 +/- 0.56 mN) (NYHA II-III). The negative inotropic potencies of nifedipine and verapamil were significantly greater in human auricular trabeculae compared to papillary muscle strips (p less than 0.05). However, on the relation between therapeutic vasoactive plasma concentrations and IC25 values, an entirely different rank order of potential negative inotropism could be observed: verapamil greater than nifedipine greater than diltiazem greater than isradipine.