Abstract

Quinidine, procaine amide, seven new antiarrhythmics, eleven antihistaminics, four local anesthetics, six antimalarials, and a few other compounds were tested for their ability to protect the canine heart from spontaneously occurring ventricular fibrillation (VF) during progressive immersion hypothermia. Several of these compounds were eliminated as "noneffective" with a high degree of statistical confidence on the basis of screening tests. Extensive tests at various doses were performed with the effective compounds for a more complete evaluation.

Quinidine was found to be effective, while procaine amide had no protective effect and appeared to precipitate VF at somewhat higher temperatures. Antazoline, methapyrilene, chlorothen (chloromethapyrilene) and doxylamine were more effective than quinidine. RP 2339 (Antergan) and Ro 2-7302 were as effective while MC 4112 (Ambonestyl) was less effective.

Most of the effective compounds produced a significant decrease in the average lethal temperatures in conjunction with the decrease in the incidence of VF. This is taken to indicate a specific action rather than a general depressant effect on the heart.

Although the majority of the effective compounds were from the class of the antihistaminics, no apparent correlation exists between the antifibrillatory activity of these drugs in spontaneous hypothermic VF (as revealed in the present tests) with any of the various pharmacological effects of this group.