Sulmazole effects on mechanical performance of hypoxic and reoxygenated isolated mammalian myocardium.

The present study intended to investigate the effects of 2-[2-methoxy-4-(methylsulfinyl)phenyl]-3H-imidazo[4,5-b]pyridine (sulmazole, AR-L 115 BS) on mechanical performance of rat myocardial fibers under hypoxia, and subsequent reoxygenation. Because of a possible caffeine-like mechanism of action of sulmazole similar experiments were performed with theophylline and the results compared. 1. Under normoxic conditions, sulmazole and theophylline displayed a positive inotropic action with acceleration of relaxation at small concentrations (sulmazole: 6.4 mumol l-1; theophylline 7.35 mumol l-1). Increasing doses led to a negative inotropic effect with slackened relaxation and loss of its load sensitivity (up to 390 mumol l-1 for sulmazole; up to 350 mumol-1 for theophylline). In agreement with other reports, the dose-effect curve was shifted towards low concentrations. 2. During ischemic crisis, therapeutic doses of sulmazole (6 mumol l-1) and theophylline (7 mumol l-1) induced no additional depression of contractility and protected relaxation. During subsequent reoxygenation, better recovery of contractility was observed without any very significant improvement of relaxation. 3. During reoxygenation beyond 120 mumol l-1, increasing doses of sulmazole depressed contractility. An additional depressive effect on mechanical performance was observed during hypoxia only for the highest dose (390 mumol-1).