Reversal of the cardiovascular effects of verapamil by calcium and sodium: differences between electrophysiologic and hemodynamic responses.

Abstract

The reversibility of verapamil-induced hemodynamic and electrophysiologic changes by i.v. 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. Increased serum Ca concentration (Ca)s to an average 6.5 meq/l abolished the depressive effects of verapamil on cardiac output and left ventricular dP/dt [change in pressure with time] and diminished drug-related hypotension by an average of 52%, but did not affect verapamil-induced prolongation of AH [atrium-His] 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 had no effect on verapamil-induced slowing of sinus rate or 2nd-degree atrioventricular (AV) block during atrial pacing. Rapid i.v. injection of 40 ml 2 M NaCl transiently raised serum Na+ concentration to 162 meq/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 19% of control value, and decreased the severity of 2nd-degree AV blocks, 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, increase of (Ca)s to 8.2 meq/l or NaCl injection following CaCl2 had no effect on AH interval or sinus rate. Ca2+ and Na+ compete with verapamil, but Na+ acts only in the presence of hypercalcemia. Verapamil effects differ in their reversibility. Ca treament may be useful in counteracting the negative inotropic effect of verapamil.