Document Detail


Cardiovascular effects of verapamil enantiomer combinations in conscious dogs.
MedLine Citation:
PMID:  9652336     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We examined the systemic and coronary hemodynamic effects of five combinations of R- and S-verapamil enantiomers (R/S; 100/0, 90/10, 80/20, 50/50, and 20/80%, respectively) in conscious dogs chronically instrumented for measurement of aortic and LV pressure, +dP/dt, subendocardial segment length, coronary blood flow velocity, and aortic blood flow. Dogs received escalating doses (0.1, 0.2, and 0.4 mg kg(-1)) of each verapamil combination over 2 min at 30 min intervals on different experimental days and peak changes in hemodynamics were recorded 2 min after each dose. All verapamil combinations increased heart rate, mean aortic blood flow, and coronary blood flow velocity and decreased calculated systemic and coronary vascular resistance. Alterations in coronary hemodynamics were most pronounced with 20/80 R/S verapamil. Racemic and 20/80 R/S verapamil decreased mean arterial and left ventricular systolic pressure, in contrast to combinations with greater concentrations of the R enantiomer. Left ventricular function was unchanged during administration of 100/0, 90/10, and 80/20 R/S verapamil. Direct negative inotropic and lusitropic effects occurred with 50/50 and 20/80 R/S verapamil. The high dose of 20/80 R/S verapamil also increased left ventricular end-diastolic pressure and the regional chamber stiffness constant, consistent with diastolic dysfunction. The results indicate that combinations of R- and S-verapamil produce differential hemodynamic and left ventricular functional effects in conscious, unsedated dogs that are dependent on the relative ratio of these enantiomers.
Authors:
P S Pagel; D A Hettrick; D Lowe; P W Gowrie; J R Kersten; Z J Bosnjak; D C Warltier
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  European journal of pharmacology     Volume:  348     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-10-26     Completed Date:  1998-10-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  213-21     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee 53226, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta / drug effects*
Blood Pressure / drug effects
Calcium Channel Blockers / administration & dosage,  pharmacology*
Coronary Circulation / drug effects*
Dogs
Dose-Response Relationship, Drug
Heart Rate / drug effects
Hemodynamics / drug effects*
Myocardial Contraction / drug effects
Stereoisomerism
Vascular Resistance / drug effects
Vasodilator Agents / administration & dosage,  pharmacology*
Ventricular Function, Left / drug effects
Verapamil / administration & dosage,  pharmacology*
Grant Support
ID/Acronym/Agency:
GM08377/GM/NIGMS NIH HHS; HL54820/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Vasodilator Agents; 52-53-9/Verapamil

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