REVERSAL OF THE CARDIOVASCULAR EFFECTS OF VERAPAMIL BY CALCIUM AND SODIUM - DIFFERENCES BETWEEN ELECTROPHYSIOLOGIC AND HEMODYNAMIC-RESPONSES

The reversibility of verapamil-induced hemodynamic and electrophysiologic changes by intravenously administered CaCl2 and NaCl was tested in 34 anesthetized open-chest dogs during verapamil infusions which produced plasma verapamil concentrations of 70-2042 ng/ml. An increase of serum calcium concentration (Ca)(s) to an average 6.5 mEq/l abolished the depressive effects of verapamil on cardiac output and left ventricular dp/dt and diminished drug-related hypotension by an average of 52%, but did not affect verapamil-induced prolongation of AH interval and slowing of sinus rate. Further increase of (Ca)(s) to an average of 8.2 mEq/l decreased AH prolongation caused by verapamil from an average of 95% to 45% of control value, but no effect on verapamil-induced slowing of sinus rate or second-degree atrioventricular (AV) block during atrial pacing. Rapid intravenous injection of 40 ml 2 M NaCl, transiently raised serum Na+ concentrations to 162 mE/l, decreased AH prolongation caused by verapamil to an average of 22% of control value, decreased slowing of sinus rate from an average of 34% to an average of 19% of control value, and decreased the severity of second-degree AV block, but had no effect on verapamil-induced complete AV block or sinus arrest. Hypernatremia had no effect on AH interval and sinus rate without prior CaCl2 infusion. In the absence of verapamil, neither increase of (Ca)(s) to 8.2 mEq/l, nor NaCl injection following CaCl2 had any effect on AH interval or sinus rate. This study suggests 1) that both Ca++ and Na+ compete with verapamil, but Na+ acts only in the presence of hypercalcemia; 2) different verapamil effects differ in their reversibility; and 3) treatment with calcium may be useful in counteracting the negative inotropic effect of verapamil.