Effects of verapamil on the blood-perfused, isolated atrium preparation of the dog heart.

Thirteen isolated canine right atria were perfused with blood conducted from a support dog. The selective injection of verapamil into the cannulated sinus node artery at a dose level above 1 mug usually induced dose-dependent negative chronotropic and negative inotropic effects. At a dose of 30 mug, verapamil caused sinus arrest in 4 cases out of 7 with marked suppression of the isometric tension development. At 100 mug, in all cases it caused sinus arrest which continued about 1 hour. When calcium chloride was injected into the sinus node artery, a positive inotropic effect was dose-relatedly produced above a dose level of 100 mug, but the threshold dose for inducing a positive chronotropic effect of calcium chloride was approximately 1 mg. On the other hand, norepinephrine when injected into the sinus node artery simultaneously induced a positive chronotropic and inotropic effect at the same threshold dose. A dose level of 10-30 mug of verapamil did not significantly inhibit positive chronotropic and inotropic responses to norepinephrine and a positive inotropic response to calcium chloride in per cent. The negative inotropic response as well as the positive chronotropic and inotropic responses to electric stimulation of the epicardium were not blocked by verapamil which caused marked suppression of the tension development.