PROTECTIVE EFFECTS OF DILTIAZEM ON THE MECHANICAL PERFORMANCE OF THE HYPOXIC MYOCARDIUM

1. To determine whether diltiazem protects the hypoxic myocardium by r educing contractile work, we have compared the effects of diltiazem an d quiescence on left ventricular (LV) papillary muscle subjected to hy poxia. Papillary muscles were obtained from male Charles River CD rats weighing 150-250 g. 2. Four groups of muscles were studied: control ( N = 6), non-stimulation (N = 10), diltiazem 10(-4) M (N = 6) and dilti azem 10(-4) M plus non-stimulation (N = 10). 3. Isolated mt LV papilla ry muscles were studied in Krebs-Henseleit solution with a calcium con centration of 2.52 mM at 28-degrees-C while contracting isometrically at a stimulation rate of 0.2 Hz. Resting tension and active isometric tension were measured. 4. Both diltiazem and quiescence significantly attenuated contracture tension during hypoxia (0.91 +/- 0.10 vs 2.26 /- 0.49 g/mm2 for diltiazem vs control, and 0.55 +/- 0.18 vs 2.26 +/- 0.49 g/mm2 for quiescence vs control). Recovery of active tension was improved in the diltiazem groups during reoxygenation (4.16 +/- 0.42 v s 3.75 +/- 0.51, 3.53 +/- 0.15 vs 2.90 +/- 0.13, 5.84 +/- 0.33 vs 6.48 +/- 0.29 and 5.98 +/- 0.90 vs 7.67 +/- 0.68 g/mm2 for diltiazem, dilt iazem non-stimulation, non-stimulation and control groups). 5. The res ults suggest that the protective effect of diltiazem during hypoxia wa s due to the reduction in energy demand of the myocardium.