Increases in myocardial cyclic GMP attenuate contractile delay in myocardial stunning

Abstract

We tested the hypothesis that the effects of myocardial stunning would be reduced by cyclic GMP in rabbit hearts. In three groups of anesthetized open-chest New Zealand white rabbits, myocardial stunning was produced by 15 min of occlusion of the left anterior descending coronary artery followed by 15 min of reperfusion repeated twice. Either control vehicle (saline plus 1% dimethyl sulfoxide) or 8-bromo-cyclic GMP (8-Br-cGMP (10–4 and 10–3 M)) was topically applied to the left ventricular surface. Hemodynamic (left ventricular and aortic pressures) and functional parameters (wall thickening, delay in onset of wall thickening, and rate of wall thickening) were determined. Coronary blood flow (microspheres) and O2 extraction (microspectrophotometry) were used to determine myocardial O2 consumption (VO2). Myocardial stunning was observed in the control group through an increased delay in onset of myocardial wall thickening (29 ± 7 versus 55 ± 16 ms) and decreased maximal rate of wall thickening (20 ± 8 versus 11 ± 3 mm·s–1). After treatment with 8-Br-cGMP 10–4 and 10–3 M, stunning did not increase the delay (37 ± 5 versus 39 ± 7 and 39 ± 7 versus 28 ± 8 ms). Myocardial stunning did not significantly alter V02. 8-Br-cGMP 10–3 M significantly decreased subepicardial V02 (6.2 ± 0.8 versus 3.7 ± 0.6 mL O2·min–1·100 g–1) and insignificantly decreased subendocardial V02 (8.6 ± 0.9 versus 6.3 ± 1.2 mL O2·min–1·100 g–1) when compared with the vehicle-treated rabbits. We conclude that increasing cyclic GMP reduced the effects of myocardial stunning in the rabbit heart by ameliorating the delay in onset of wall thickening and decreasing the local O2 costs in the stunned region. Key words: cyclic GMP, myocardial stunning, O2 consumption, ischemia, reperfusion, wall thickening, rabbit.