Faculty Collaboration Database

Cardiovascular effects of verapamil enantiomer combinations in conscious dogs. Eur J Pharmacol 1998 May 08;348(2-3):213-21

Date

07/04/1998

Pubmed ID

9652336

DOI

10.1016/s0014-2999(98)00145-9

Scopus ID

2-s2.0-0032496071 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

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.

Author List

Pagel PS, Hettrick DA, Lowe D, Gowrie PW, Kersten JR, Bosnjak ZJ, Warltier DC

MESH terms used to index this publication - Major topics in bold

Animals
Aorta
Blood Pressure
Calcium Channel Blockers
Coronary Circulation
Dogs
Dose-Response Relationship, Drug
Heart Rate
Hemodynamics
Myocardial Contraction
Stereoisomerism
Vascular Resistance
Vasodilator Agents
Ventricular Function, Left
Verapamil