Lack of correlation of verapamil plasma level with cumulative protective effects against halothane--epinephrine ventricular arrhythmias.

The effect of verapamil, 0.2 mg/kg i.v. over 30 s, on the amount of epinephrine required to elicit a reproducible ventricular arrhythmia during 0.9% halothane in oxygen anesthesia was investigated in two groups of dogs after three consecutive doses of verapamil given at 90 (group I) and 120 min (group II) intervals, respectively. Verapamil caused a stepwise cumulative increase in the arrhythmogenic dose of epinephrine in both groups despite plasma verapamil levels that declined to low levels (28 and 22 ng/ml, respectively) between doses. Control epinephrine arrhythmogenic doses were 2.89 +/- 0.54 and 2.74 +/- 0.19 microgram/kg/min (mean +/- SEM), respectively, for groups I and II, and rose to 4.58 +/- 0.72 and 4.55 +/- 0.30 microgram/kg/min after the first verapamil dose, to 6.20 +/- 0.74 and 6.13 +/- 0.40 microgram/kg/min after the second verapamil dose, and 8.16 +/- 0.85 and 8.09 +/- 0.95 microgram/kg/min after the third verapamil dose, respectively. All postverapamil epinephrine arrhythmogenic dose values were significantly elevated above control and above the preceding values, although there was no significant difference between the two groups. Changes in heart rate or blood pressure were similar among the three doses of verapamil in each group. These results can be interpreted to indicate that, unlike hemodynamic effects that appear to parallel plasma verapamil concentrations, the protective effects of verapamil against halothane--epinephrine ventricular arrhythmias may not be accurately reflected by plasma verapamil levels and may be significantly present when plasma levels are too low to cause measurable hemodynamic effects.