Effects of sustained isometric handgrip exercise on platelet aggregability and left ventricular performance in patients with ischemic heart disease, and cyclic AMP phosphodiesterase inhibitor EG626 pretreatment

Abstract

The effects of sustained isometric handgrip exercise on platelet aggregability and the left ventricular function were assessed in 29 patients with ischemic heart disease (Table 1) on placebo and EG626, a newly synthesized cyclic AMP phosphodiesterase inhibitor. The platelet aggregability was assessed by using a new device (Sano, 1974) which avoids centrifugation and needs only a small amount of citrated blood (Fig. 1). The left ventricular performance was estimated by a non-invasive technique, systolic time intervals. Parameters of systolic time intervals (LVET, PEP, ICT and PEP/ET) were expressed as indices following Motomiya's multiple regression equations (Table 2).RESULTS (1) Platelet Aggregability: On placebo, an enhancement of platelet aggregability was observed after isometric handgrip exercise in patients with ischemic heart disease but not in healthy control subjects. The enhancement of platelet aggregability was prevented by pretreatment of EG626, administered orally 90 minutes prior to the exercise (Fig. 1).(2) Left Ventricular Function (Fig. 3): a) At Rest: Systolic blood pressure was significantly lower on EG626 pretreatment than on placebo (p<0.01). Heart rate, diastolic blood pressure and all indices of STI's were not different between two regimens.b) During Handgrip Exercise: The increase in heart rate by exercise was significantly smaller on EG626 pretreatment. The increase in systolic and diastolic blood pressures was not different between two regimens. Handgrip exercise produced significant decrease in LVETi on both placebo and EG626 regimens (p<0.05 and 0.01 respectively). However these decrements were not statisitically different between two regimens. Handgrip exercise produced significant increase in PEPi, ICTi and PEP/ETi both on placebo and EG626 (p<0.01 each). The increment was smaller on EG626 in PEPi and PEP/ETi (p<0.05 and 0.01 respectively) and not different in ICTi between two regimens.The foregoing results indicate the followings: Handgrip isometric exercise produced significant deterioration in systolic time intervals indicating decrease in stroke volume, cardiac output and also probable impairment in myocardial contractility in patients with ischemic heart disease. EG626 pretreatment improved above deterioration in the left ventricular function induced by the exercise.These effects of EG626 on platelet aggregability and the left ventricular performance could be attributed to the cyclic AMP level as this compound reportedly increases c-AMP level in platelet and myocardium.