Effect of Quinidine, Procaine Amide and Mersalyl on Lethal Dose of Ouabain in Isolated Dog Heart.

Abstract

Digitalis is often used in combination with one or more of the following drugs: quinidine, procaine amide, mercurial diuretics. The endeffect of a sufficiently large dose of digitalis is ventricular fibrillation. preceded, as a rule: by ventricular ectopic rhythms. Quinidine is used for the treatment of ventricular ectopic rhythms, even those that are produced by digitalis. On the other hand, textbooks attribute to quinidine the property of producing ventricular premature beats. ventricular tachycardia and ventricular fibrillation, in other words, precisely those effects which it is supposed to suppress or prevent. Procaine amide is used, like quinidine, to suppress ventricular ectopic rhythms including those produced by digitalis( 1 ) , but nobody has described an arrhythmia-producing effect by procaine amide. The combined use of the drugs mentioned above, particularly digitalis and quinidine, has been the subject of much debate and investigation ( 2 ) . It thus appeared desirable to study the quantitative aspects of these drug combinations using isolated hearts.Methods and materials. Dog heart-lung preparations were performed by the conventional procedure using pentobarbital anesthesia. The blood donors were anesthetized with chloroform. The blood volume was about 900 cc and the resistance was maintained a t 6.8 cm Hg. The method of Farah ( 3 . 3 ) was used in measuring the lethal dose of ouabain. The rate of infusion was not far from the "optimal" rate. i.e., the rate below which there is no further decrease in the lethal dose. In all experiments with intact dogs pentobarbital anesthesia was used with artificial respiration. The following brands of drugs were used: Ouabain, E. Merck, Darmstadt ; Quinidine sulfate, Jlallinckrodt, V.S.P. : Procaine amide. (Pronestyl) Squibb; Jlersalyl. (Gortulin) n'inthrop. *This study has been supported by a grant from -. -__-__ the American Heart Association.Results. Oiiabain controls. -4s controls we have utilized Farah's (3,4) results most of which were obtained in this laboratory. In addition, we have performed a few more experiments which are essentially in agreement with those of Farah (Table I).Small amounts of quinidine sulfate (20 mg or less) , when added to the venous reservoir of the heart-lung Ouabain + quinidine.

Effect of Reserpine and Pronethalol on the Therapeutic and Toxic Actions of Digitalis in the Dog Heart‐lung Preparation

“…Furthermore, the changed electrocardiographic pattern-namely, block, idioventricular rhythm and standstill-is very reminiscent of the action of quinidine on isolated dog hearts and intact dogs. In a previous paper (Fawaz, 1955) it was shown that doses of quinidine ranging between 30 and 140 mg, and which were sufficient to depress the myocardium as judged by a decreased output and increased right atrial pressure, did not influence the lethal dose of ouabain in the dog heart-lung preparation but that in all cases the terminal arrhythmia was indeed ventricular fibrillation. Benfey & Varma (1966) working on the isolated guinea-pig atrium reported that pronethalol and propranolol possess an anti-fibrillatory property equal to that of quinidine and that it is not directly related to their /3-blocking action.…”