Short-Term Hemodynamic Effects of Mibefradil in Dogs With Chronic Heart Failure: Comparison With Diltiazem

Despite the marked vasodilator and antiischemic actions of existing calcium channel blockers, their use in the treatment of patients with chronic heart failure (HF) remains highly controversial. We compared the short-term hemodynamic effects of i.v. mibefradil, a predominant T-type calcium channel blocker with only partial L-type calcium channel antagonism, and diltiazem, a selective L-type calcium channel antagonist in dogs with chronic HF. Each of three drugs namely, mibefradil, diltiazem and normal saline (as placebo control), were studied in random order (6 days between each drug intervention), in each of 8 dogs with chronic HF produced by multiple intracoronary microembolizations. Intravenous mibefradil and diltiazem were administered as a 100 μg/kg bolus followed by a continuous infusion of 6 and 4 μg/kg/min, respectively, for 15 min. Equal volumes of normal saline were administered in an identical fashion. In all instances, hemodynamics were obtained at baseline and at 5, 10, 15, 30 and 60 min after bolus drug administration. Left ventriculograms were obtained at baseline, and at 15 and 60 min after bolus drug administration. Saline infusion had no effects on hemodynamic or angiographic indexes of left ventricular (LV) function. At 15 min, mibefradil caused significant increases of LV stroke volume and LV ejection fraction compared to baseline (40 ± 5 vs. 31 ± 3 ml, P vs. 28 ± 1%, P