The effect of thioridazine and promazine in reducing the potassium loss from isolated perfused rat hearts.

Abstract

Electrically stimulated isolated rat hearts were perfused with a Ringer solution containing a low concentration of K+. At the end of a control period of 20 min. the cumulative K+ loss from the hearts was approximately 30 meq./kg dry weight. This value was used in each experiment as reference (100 per cent) for the total loss found after a subsequent additional test period of 30 min. The addition of promazine and thioridazine to the perfusate at the end of the control period reduced the further K+ loss. The values found in the different groups at the end of the test period were: Control group (10 hearts): 154 ± 11.6 per cent; with promazine 10‐5 M added (8 hearts): 103 ± 5.6 per cent; with promazine 2.5 × 10‐5 M added (10 hearts): 74 ± 10.5 per cent and with thioridazine 10‐5 M added (8 hearts): 110 ± 5.8 per cent. In another type of experiments, ouabain 1.5 × 10‐6 M was added at the end of the control period. This drug caused an increased K+ loss (181 ± 14.2 per cent) and ventricular fibrillation in 6 out of 8 hearts. Promazine 2.5 × 10‐5 M added before ouabain, prevented the development of fibrillation in another group of 7 hearts, and also markedly reduced the K+ loss. It is concluded that phenothiazines reduce the K+ permeability of the heart muscle membranes.