[Electrophysiologic effects of a spironolactone-altizide combination on the isolated rat heart]

The association of spironolactone and altizide is effective in the treatment of some forms of resistant oedemas. Our aim was to determine whether the renal effects of this association were associated with abnormal cardiac cellular electrophysiological changes. Isolated rat hearts perfused by the retrograde aortic approach and paced at 200 beats per minute were studied. Cardiac cellular activation was measured by floating microelectrodes in the subepicardial layers of the left ventricle. The following parameters were analysed: the duration of the action potential at 25% and 75% of repolarisation (DAP25 and DAP75), the timing and amplitude of the point of rupture of the action potential (T.PR and A.PR), the amplitude of the action potential at 40 ms (A.40). A simultaneous variation of 3 of these parameters was considered to be a significant change. The animals were given an intraperitoneal injection of either 2.5 mg/kg or 10 mg/kg of spironolactone, 0.25 mg/kg or 1 mg/kg of altizide or any association of these two drugs at the given dosages. Spironolactone alone at these dosages did not cause any change in the electrical activation of the rat ventricular myocardial cell. On the other hand, 1 mg/kg of altizide produced a significant increase in the duration of the ventricular action potential at zero potential (DAP25) and during the plateau phase (T.PR and A.40). These changes, which could be related to the potassium metabolism, were abolished when altizide was associated with spironolactone. This is probably a similar effect to that of the prevention of hypokalaemia and low intracellular potassium concentrations when associating a potassium sparing drug with hypokalaemic diuretics.