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Research ArticleArticle

Differential Effects of Mibefradil, Verapamil, and Amlodipine on Myocardial Function and Intracellular Ca2+ Handling in Rats with Chronic Myocardial Infarction

Jiang-Yong Min, Steffen Sandmann, Achim Meissner, Thomas Unger and Ruediger Simon
Journal of Pharmacology and Experimental Therapeutics December 1999, 291 (3) 1038-1044;
Jiang-Yong Min
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Steffen Sandmann
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Achim Meissner
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Thomas Unger
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Ruediger Simon
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Abstract

Mibefradil is a selective T-type Ca2+ channel blocker that exerts a potent vasodilating but weak inotropic action. The present study compared mibefradil with traditional L-type Ca2+ channel blockers in regard to the effects of chronic oral administration on hemodynamics, contractility, and intracellular Ca2+ handling in failing myocardium from postinfarction rats. Male Wistar rats with ligation-induced myocardial infarction were assigned to placebo or treatment with mibefradil (10 mg/kg/day), verapamil (8 mg/kg/day), or amlodipine (4 mg/kg/day) by oral gavage starting 7 days before the induction of myocardial infarction. Six weeks after myocardial infarction, hemodynamic measurements were performed in conscious animals. In addition, isometric force and free [Ca2+]i were determined in isolated left ventricular papillary muscles. Placebo-treated rats exhibited a decreased mean atrial pressure, an increased left ventricular end-diastolic pressure, and a reduced rate of pressure rise compared with sham-operated animals. Mibefradil treatment significantly improved all of these parameters, whereas both amlodipine and verapamil exerted only minor effects. β-Adrenergic stimulation with isoproterenol (ISO) enhanced contractility and Ca2+ availability in papillary muscles from sham-operated rats, whereas the ISO-induced inotropic effect in muscles from placebo-treated rats was severely blunted. Chronic mibefradil treatment significantly improved the inotropic response to ISO stimulation, although the Ca2+iavailability appeared to be less than in muscles from placebo-treated animals. In contrast, both verapamil and amlodipine did not restore the inotropic and Ca2+i modulating effect of ISO in remodeled myocardium. Thus, T-type Ca2+ current appears to be of pathophysiological relevance in postischemic reperfused myocardium.

Footnotes

  • Send reprint requests to: Achim Meissner, M.D., Department of Cardiology, University of Kiel, Schittenhelmstrasse 12, D-24105 Kiel, Germany. E-mail: meissner{at}cardio.uni-kiel.de

  • Abbreviations:
    CCB
    calcium channel blocker
    MI
    myocardial infarction
    MAP
    mean arterial pressure
    LVEDP
    left ventricular end-diastolic pressure
    DT
    developed tension
    ISO
    isoproterenol
    • Received May 12, 1999.
    • Accepted August 12, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 291 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 3
1 Dec 1999
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Research ArticleArticle

Differential Effects of Mibefradil, Verapamil, and Amlodipine on Myocardial Function and Intracellular Ca2+ Handling in Rats with Chronic Myocardial Infarction

Jiang-Yong Min, Steffen Sandmann, Achim Meissner, Thomas Unger and Ruediger Simon
Journal of Pharmacology and Experimental Therapeutics December 1, 1999, 291 (3) 1038-1044;

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Research ArticleArticle

Differential Effects of Mibefradil, Verapamil, and Amlodipine on Myocardial Function and Intracellular Ca2+ Handling in Rats with Chronic Myocardial Infarction

Jiang-Yong Min, Steffen Sandmann, Achim Meissner, Thomas Unger and Ruediger Simon
Journal of Pharmacology and Experimental Therapeutics December 1, 1999, 291 (3) 1038-1044;
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