PREVENTION OF VENTRICULAR FIBRILLATION DURING INDUCED HYPOTHERMIA BY N, N-DIISOPROPYL-N'-ISOAMYL-N'-DIETHYLAMINOETHYLUREA (P-286)

¹ Department of Pharmacology, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania

The adrenal medulla was found to play a significant role in the production of spontaneous ventricular fibrillation occurring during induced hypothermia in dogs. Adrenal venous blood epinephrine levels and myocardial epinephrine content were found to be increased markedly at a temperature which coincided with the production of ventricular fibrillation (22°C). This increase in the epinephrine output from the adrenal medulla was shown to be a neurally mediated phenomenon. Control animals died of ventricular fibrillation at 21.4 ± 028°C, whereas those treated with N, N-diisopropyl-N'-isoamyl-N'-diethylaminoethylurea (P-286) died in cardiac asystole at 11.1 ± 0.75°C. P-286 was found to prevent any increase in myocardial and adrenal venous blood epinephrine content occurring during hypothermia and also appeared to possess direct antiarrhythmic and antifibrillatory properties. P-286 appears to prevent ventricular fibrillation during hypothermia in dogs because of its direct antiarrhythmic and antifibrillatory properties and because it prevents the release of epinephrine from the adrenal medulla.