TY - JOUR T1 - EFFECT OF QUINIDINE AND PROCAINE AMIDE UPON ACETYLSTROPHANTHIDIN CARDIOTOXICITY JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 366 LP - 373 VL - 143 IS - 3 AU - Benedict R. Lucchesi AU - Robert Shivak Y1 - 1964/03/01 UR - http://jpet.aspetjournals.org/content/143/3/366.abstract N2 - Previous investigators, employing a variety of experimental procedures, have attempted to ascertain whether or not there exists an increased susceptibility to the cardiotoxic actions of the digitalis glycosides when used in conjunction with quinidine or procaine amide. The experimental results have not been in agreement. The possible reasons for these discrepancies have been discussed. The present study has attempted to investigate this problem under carefully controlled conditions using the acetylstrophanthidin titration procedure previously described by Lown and Levine (1954). The previous administration of quinidine gluconate or procaine amide HCl to the experimental animal resulted in a significant increase in the dose of acetylstrophanthidin required to produce cardiotoxicity as evidenced by the onset of ventricular tachycardia, idioventricular rhythms and ventricular fibrillation. The doses of quinidine gluconate employed in this study have included those resulting in therapeutic plasma concentrations of the antiarrhythmic agent. These data in the experimental animal demonstrate that the previous administration of nontoxic doses of quinidine do not have a synergistic action with the cardiotoxic effects of acetylstrophanthidin. The results obtained with procaine amide are in agreement with those obtained by previous investigators employing similar experimental techniques (Lown and Levine, 1954). The clinical significance of these results is discussed. Caution is advised in attempting to apply results obtained under controlled experimental conditions to therapeutic situations in man. The Williams & Wilkins Company ER -