Cyclic GMP reduces myocardial stunning through non-cyclic GMP protein kinase mechanisms

Abstract

We tested the hypothesis that myocardial stunning would be reduced by increased cyclic GMP and cGMP protein kinase activity. Hearts were instrumented in eight open-chest anesthetized dogs. The left anterior descending coronary artery (LAD) was occluded for 15 minutes followed by a 30-minute recovery and infusion of 8-Bromo-cGMP (0.1 and 1 microg/kg/min) during functional and metabolic data collection. Myocytes from circumflex and LAD regions were then used to obtain data at baseline, with 8-Br-cGMP (10(-7, -6, -5) M) and KT5823 10(-6) M, cGMP protein kinase inhibitor. The in vivo time delay of regional shortening increased significantly from 55 +/- 12 to 99 +/- 3 msec following stunning, but was reduced to 81 +/- 2 by 1 microg/kg/min 8-Br-cGMP. The % regional work during systole decreased during stunning (93 +/- 2 to 76 +/- 8%), but was restored by 8-Br-cGMP (91 +/- 7). Stunning lengthened the time of myocyte contraction and relaxation and reduced baseline shortening. 8-Br-cGMP reduced myocyte shortening in both regions. However, KT5823 only restored myocyte shortening in controls. These data indicated that regional myocardial stunning could be reduced by cyclic GMP but this appeared to be through non-cGMP protein kinase mechanisms.