ENDOTHELIN-1 EXACERBATES DIASTOLIC STUNNING IN CONSCIOUS DOGS

The purpose of this study was to examine the effects of endothelin-1 (ET-1) on ''diastolic stunning'' in the postischemic myocardium. In 14 conscious dogs receiving either placebo (n = 7) or ET-1 (2.5 ng . kg-1 . min-1, n = 7), left ventricular (LV) hemodynamics and regional wall motion (systolic segmental shortening by sonomicrometry and the ischemic-nonischemic regional asynchrony during isovolumic relaxation) were assessed at baseline, during 10 min of left anterior descending coronary artery occlusion (CAO) and at 60 min after reflow (R-60). During CAO, the ischemic segment shortening was severely depressed and both regional asynchrony and LV relaxation time constant were significantly increased in the placebo and ET-1 groups. At R-60, this LV diastolic dysfunction recovered to baseline conditions in the placebo group but was still present in the ET-1 group. Because coronary and myocardial blood flow returned to the baseline level at R-60 in both groups, the deleterious effects of ET-1 on diastolic stunning are probably mediated by its direct action on the myocardium.