Chronic effects of tolbutamide on myocardial tension during ischemia and reperfusion in perfused hearts isolated from insulin dependent and non insulin dependent diabetic rats

The chronic effects of tolbutamide on myocardial contractility of the diabetic heart during ischemia and reperfusion were evaluated in perfused, isolated rat hearts. Five experimental groups were used: (1) control rats (C), (2) insulin dependent diabetic rats (IDDM, single intravenous injection of 60 mg/kg streptozotocin (STZ) in male Sprague-Dawley rats), (3) non insulin dependent diabetic rats (NIDDM; single subcutaneous injection of 90 mg/kg STZ in 5 day neonates), (4) tolbutamide-treated IDDM and (5) NIDDM (T-IDDM, T-NIDDM; giving tolbutamide 100 mg/kg/day for 6 weeks via an orogastric tube every day, respectively). At 14 weeks of age, experiments were performed using a Langendorff perfused heart preparation. After equilibration, T (myocardial developed tension), +dT/dt (contraction velocity), -dT/dt (relaxation velocity) and RT (resting tension) were measured during a 15 min period of global ischemia, followed by reperfusion for 20 min. Basal values of T increased in both T-IDDM and T-NIDDM, compared to IDDM and NIDDM, respectively. The percent recovery rate of +dT/dt in T-IDDM increased significantly during both ischemia and reperfusion, but the change in T-NIDDM was not significant. The recovery rates of -dT/dt in T-IDDM and T-NIDDM were significantly higher throughout reperfusion than in IDDM and NIDDM, respectively. On the other hand, that of T in T-IDDM and T-NIDDM were significantly higher than IDDM and NIDDM throughout ischemia and reperfusion, respectively. The RT was significantly higher in IDDM than in C and NIDDM throughout ischemia and reperfusion. The RT was significantly lower during ischemia in IDDM, but it did not differ significantly from IDDM during reperfusion. These results indicate that chronic oral administration of tolbutamide directly improved myocardial contractility throughout ischemia and reperfusion regardless of the improvement of glycemia. The improvement was also greater in IDDM than in NIDDM.