Role of ischemia-reperfusion on myocardial cyclic AMP and cyclic AMP phosphodiesterase: Effects of amrinone on regional myocardial force and shortening

This study tested the hypothes is that a reperfused ischemic myocardial region of the dog heart would be unable to increase its function in response to amrinone, a specific cyclic AMP phosphodiesterase (cAMP-PDE) inhibitor, due to loss of cAMP-PDE activity in the region. The global contractility (+dP/dt_max), regional percent shortening (ultrasonic crystals), and developed force (miniature force gauge) were measured on a continuous basis throughout a 6-hour experiment and regional blood flow (radioactive microspheres) in open-chest pentobarbital-anesthetized mongrel dogs. The left anterior descending coronary artery (LAD) was isolated and ligated for 2 hours and allowed to reperfuse for 4 hours. This myocardial region was compared to a nonischemic region supplied by the circumflex artery. At the end of the 4-hour reperfusion period, 9 dogs were treated with amrinone (5 mg/kg) and three dogs were not treated with amrinone. The hearts were rapidly excised and frozen in liquid nitrogen. Cyclic AMP and cAMP-PDE activity was determined in homogenates of myocardial tissue. Blood flow decreased during occlusion in the LAD region and returned toward control with reperfusion. Flow increased nonsignificantly with amrinone. The basal cyclic AMP content of the two regions was not different. The cAMP-PDE activity was reduced 24% in the LAD region compared to the control region. There were no ischemia-induced changes in the enzyme characteristics. These experiments demonstrated increased global function in the ischemic reperfused myocardium after amrinone was administered (dP/dt_max: 2092 ± 538 to 3277 ± 688 mmHg/sec). In the control region, the force increased (+50%) and percent shortening increased (+53%) after amrinone. The amrinone-induced changes in force and percent shortening measured in the LAD region were not significantly different from the control region, although the increase in shortening was not significant. The data indicate that the ischemic reperfused myocardium responded almost as well to amrinone as the control region, despite reduced cAMP-phosphodiesterase activity.