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(Circulation. 1999;99:305-311.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Unique Cardioprotective Action of the New Calcium Antagonist Mibefradil

Rainer Schulz, MD; Heiner Post, MD; Andreas Jalowy, MD; Ulrich Backenköhler, MD; Hilmar Dörge, MD; Christian Vahlhaus, MD; Gerd Heusch, MD

From the Abteilung für Pathophysiologie, Zentrum für Innere Medizin des Universitätsklinikums Essen, Germany.

Correspondence to Prof Dr Gerd Heusch, FESC, FACC, Abteilung für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstraße 55, 45122 Essen, Federal Republic of Germany.

Background—Mibefradil is a calcium antagonist with few negative inotropic effects at therapeutic concentrations.

Methods and Results—The effect of mibefradil on infarct size (IS) was compared with those of placebo, amlodipine, and verapamil in 64 anesthetized pigs. In placebo pigs, after 90 minutes of ischemia and 120 minutes of reperfusion, IS (by triphenyl tetrazolium chloride staining) was 15.3±10.8% (SD) of the area at risk. Mibefradil (0.60 mg/kg IV) reduced heart rate and left ventricular (LV) pressure, and IS was 1.9±3.9% (P<0.05 versus placebo). Verapamil (0.15 mg/kg IV) also decreased heart rate, LV pressure, and IS (6.1±4.2%, P<0.05 versus placebo). Amlodipine (0.20 mg/kg IV) did not alter heart rate, LV pressure, or IS (9.9±5.4%, P=NS versus placebo). When heart rate was maintained constant by left atrial pacing and LV pressure was adjusted to that of the placebo group by an intra-aortic balloon, mibefradil still decreased IS (3.8±3.0%, P<0.05 versus placebo), but verapamil did not (11.6±8.3%, P=NS versus placebo). With glibenclamide infusion, mibefradil no longer reduced IS (13.1±4.3% versus 17.8±5.6% with glibenclamide alone, P=NS).

Conclusions—The IS-limiting effect of mibefradil, in contrast to that of verapamil, was not dependent on favorable hemodynamics but was abolished by glibenclamide, suggesting a direct cardioprotective action of mibefradil.

Key Words: calcium • mibefradil • myocardial infarction

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