Document Detail

Unique cardioprotective action of the new calcium antagonist mibefradil.
MedLine Citation:
PMID:  9892599     Owner:  NLM     Status:  MEDLINE    
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.
R Schulz; H Post; A Jalowy; U Backenköhler; H Dörge; C Vahlhaus; G Heusch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  99     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-02-23     Completed Date:  1999-02-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  305-11     Citation Subset:  AIM; IM    
Abteilung für Pathophysiologie, Zentrum für Innere Medizin des Universitätsklinikums Essen, Germany.
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MeSH Terms
Amlodipine / pharmacology
Benzimidazoles / pharmacology*
Calcium Channel Blockers / pharmacology*
Glyburide / pharmacology
Heart / drug effects*
Heart Rate / drug effects
Heart Ventricles / drug effects
Myocardial Infarction / pathology
Tetrahydronaphthalenes / pharmacology*
Verapamil / pharmacology
Reg. No./Substance:
0/Benzimidazoles; 0/Calcium Channel Blockers; 0/Tetrahydronaphthalenes; 10238-21-8/Glyburide; 116644-53-2/Mibefradil; 52-53-9/Verapamil; 88150-42-9/Amlodipine
Comment In:
Circulation. 1999 Jan 19;99(2):198-200   [PMID:  9892582 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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