Nitroprusside reverses lengthened time of contraction in stunned canine cardiac myocytes.

Abstract

We tested the hypothesis that stunning reduces the function of isolated canine ventricular myocytes and that nitroprusside (NP) reverses this effect. After stunning (15 min occlusion, 45 min reperfusion), isolated myocytes were prepared from control (circumflex artery) and stunned (left anterior descending) regions of the hearts of seven dogs. The myocytes were examined at baseline and with NP (10(-6,-5,-4) M) for oxygen consumption (MVO2, nl O2/min/10(5) cells), cyclic guanosine monophosphate (cyclic GMP; fmol/10(5) cells), and cell contraction. Basal MVO2 was not significantly different between control and stunned myocytes (888 +/- 108 vs. 716 +/- 94). NP caused a dose dependent decrease in MVo2 (control, 262 +/-51; stunned, 287 +/- 59, NP 10(-4) M). Basal cyclic GMP levels were comparable between control and stunned myocytes (117 +/-28 vs. 124 +/- 18). NP produced a similar dose-dependent increase in cyclic GMP in control and stunned myocytes. Baseline cell shortening (%) was similar in control vs. stunned myocytes (12.1 +/- 1.2 vs. 11.0 +/- 0.9). NP reduced shortening (6.9 +/- 0.3 vs. 7.3 +/- 0.5, NP 10(-4) M). There was no baseline difference in maximal rate of shortening (microm/s) between control and stunned myocytes (164 +/- 14, 157 +/- 20). With NP, a decrease in the maximal rate of shortening was seen in both groups (128 +/- 12, 139 +/- 21, NP 10(-4) M). The time of contraction (s) was significantly longer in stunned (0.20 +/- 0.03) versus control (0.13 +/- 0.01). NP significantly lengthened the time of contraction in controls in a dose-dependent manner (0.33 +/-0.05, NP 10(-4) M). In stunned myocytes, however, low-dose NP (10(-6) M) caused a decrease in the time of contraction (0.15 +/-0.03). High-dose NP (10(-4) M) did not significantly lengthen time of contraction in stunned cells (0.23 +/- 0.02). The time of relaxation followed a similar pattern. We conclude that part of the effect of NP in low doses in stunned myocardium is to reduce the lengthened time of contraction and relaxation characteristic of stunning.