PHARMACOLOGY OF ACONITINE-INDUCED AUTOMATICITY ON IN VITRO CAT MYOCARDIAL PREPARATIONS. II. EFFECTS OF REFRACTORY PERIOD PROLONGATION, REDUCED SODIUM AND TETRODOTOXIN

¹ Department of Pharmacology, University of Oregon Medical School, Portland, Oregon

Dose-effect curves were obtained for nine antiarrhythmic substances utilizing the maximal driving frequency of cat papillary muscles (an indirect method for determining prolongation of the refractory period). The order of potency was: d-and dl-propranolol > quinidine, dl-pronethalol and lidocaine > diphenylhydantoin > procainamide > dl-practolol. Bretylium showed only slight activity. From the dose-effect curves obtained, the concentrations which prolonged the refractory period by 20% (RPP₂₀) were derived. By strict adherence to the doses derived from the RPP₂₀ potency ratios the heart rate of aconitine-induced tachycardia in the cat Langendorff preparation was returned to preaconitine heart rate levels after addition of the five substances studied (dl-propranolol, lidocaine, procainamide, quinidine and practolol). Thus, there appears to be a relationship between the ability of a substance to prolong the refractory period of cat papillary muscle and its ability to reverse the tachycardia produced by aconitine in the cat Langendorff preparation. In addition, we observed that aconitine-induce automaticity and tachycardia could be reversed by substituting perfusate containing half the normal concentration of sodium or by the addition of tetrodotoxin (0.1-1 µg/ml). These results support the view that aconitine-induced automaticity and tachycardia may be due to an increase in sodium permeability.