Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs: VII. Verapamil and thiopental.
To assess the role of basal anesthesia in the negative inotropic properties of verapamil, the effect of thiopental (30 mg/kg followed by 3.5 mg.kg-1.min-1) on verapamil pharmacokinetics (200 micrograms/kg iv; n = 6) and its pharmacodynamics (3 and 6 micrograms.kg-1.min-1; n = 11) in chronically instrumented dogs was studied. In the presence of thiopental, verapamil pharmacokinetics remained essentially unchanged. In contrast, anesthesia altered verapamil hemodynamic properties. In the conscious animal verapamil infusions increased heart rate (14 +/- 3 and 27 +/- 4 beats/min, respectively), cardiac output (0.22 +/- 0.07 and 0.24 +/- 0.08, l/min, respectively) and PR interval (14 +/- 2 and 25 +/- 6 ms, respectively) and slightly decreased dP/dt (-315 +/- 114 and -419 +/- 106 mmHg/s, respectively). Systemic vascular resistance (SVR) decreased at the low dose (-2.7 +/- 0.7 mmHg.1.min-1), and stroke volume decreased at the high dose (-4.4 +/- 0.6 ml). Yet the presence of thiopental resulted in an accentuation of verapamil-induced tachycardia (27 +/- 7 and 31 +/- 6 beats/min, respectively), and a decrease in stroke volume (-5.3 +/- 2.0 and -6.3 +/- 2.1 ml, respectively). At 3 micrograms.kg-1.min-1 verapamil did not increase PR interval, cardiac output, or vasodilation. Finally, at 6 micrograms.kg-1.min-1 verapamil did not decrease dP/dt and increased renal blood flow (21.8 +/- 6.4 ml/min). These data provide evidence that the negative inotropic properties of verapamil are more pronounced in the presence of thiopental. However, the role of basal anesthesia appears to be limited.
Hill
D C
DC
Department of Anesthesiology, Baylor College of Medicine, Houston.
Wouters
P F
PF
Chelly
J E
JE
Doursout
M F
MF
Abernethy
D R
DR
Hartley
C J
CJ
Merin
R G
RG
D000818:Animals; D003864:Depression, Chemical; D004285:Dogs; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D013874:Thiopental / Q000494:pharmacology*; D014700:Verapamil / Q000493:pharmacokinetics / Q000494:pharmacology*
D014700:Verapamil; D013874:Thiopental