EFFECTS OF PROMETHAZINE ON THE ISOLATED PERFUSED RAT-HEART

1. 1. Perfusion of hearts from normal male rats with promethazine (50-5000 ng) containing Krebs-Ringer bicarbonate buffer caused a profound bradycardia at each dose studied, and at the highest concentration, cardiac arrest occurred between 15 and 30 min after exposure to the drug. 2. 2. Coronary flow showed either a slight increase or no change as a consequence of perfusion with promethazine-containing medium. 3. 3. Promethazine (5000 ng/ml) decreased isometric systolic tension to 37% of control by 15 min, after which cardiac arrest occurred. Diastolic tension increased simultaneously at 5000 ng/ml whereas at lower concentrations, it decreased over the 60 min perfusion period. 4. 4. PR and QT intervals increased following perfusion with promethazine, and its effects were greatest at 1000 and 5000 ng/ml respectively. 5. 5. Although promethazine caused pronounced alterations in mechanical and electrical activity, it had no effect, on the biochemical functions which we measured. 6. 6. There was no evidence of promethazine-induced early myocardial ischemia, as determined by histochemical methods, and no drug-induced lesions, gross or microscopic, were found in any of the hearts studied. © 1979.