Determinants of acute hemodynamic and electrophysiologic effects of verapamil in humans: role of myocardial drug uptake.
To examine the relationship between myocardial verapamil content (MVC) and acute effects in humans, coronary sinus catheterization was used in 22 patients to determine myocardial uptake of verapamil after bolus intravenous (i.v.) verapamil (4 mg) injection. Verapamil-induced effects on hemodynamic and electrophysiologic parameters were measured simultaneously and correlated with MVC per unit baseline coronary sinus blood flow (MVC:F). Myocardial uptake of verapamil was rapid: peak MVC (1.2 +/- 0.2% of injected dose) occurred at 5.4 +/- 0.4 min; at 30 min, residual MVC was 71.1 +/- 3.4% of maximum. Peak MVC:F in individual patients was inversely related to the extent of coronary artery disease (p less than 0.005) but not to left ventricular (LV) systolic function. Verapamil produced significant (p less than 0.001) early reductions in arterial pressure and systemic vascular resistance (SVR); cardiac index (CI) increased, left ventricular (LV) positive dP/dt was unchanged. Verapamil prolonged (p less than 0.01) PR and AH intervals (maximum at 12-18 min) and atrioventricular (AV) nodal effective and functional refractory periods (ERP, FRP) (maximum at 30 min). In individual patients, the extent of changes in AH intervals (r = 0.69; p less than 0.05) and LV dP/dt (r = 0.62; p less than 0.05) correlated with peak MVC:F. We conclude that after i.v. injection, verapamil uptake by the human myocardium is rapid and more extensive in patients with minor coronary artery disease. Despite the hysteresis between MVC and drug effects, MCV is a determinant of inotropic and electrophysiologic effects of verapamil.
Powell
A C
AC
Department of Cardiology, Austin Hospital, Heildelberg, Victoria, Australia.
Horowitz
J D
JD
Kertes
P J
PJ
Hasin
Y
Y
Syrjanen
M L
ML
Henry
C A
CA
Sartor
D M
DM
Louis
W J
WJ
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D006328:Cardiac Catheterization; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000503:physiopathology*; D004341:Drug Evaluation; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D014700:Verapamil / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
D014700:Verapamil