EFFECTS OF ENDOTHELIN-RECEPTOR ANTAGONISM WITH PD156707 ON MYOCARDIALSTUNNING IN SWINE

Endothelin (ET) has been proposed to play a role in the pathogenesis o f myocardial ischemia/reperfusion injury. The potential role of ET in myocardial stunning has not been examined, Therefore we tested the hyp othesis that selective blockade of ETA receptors with PD156707 {sodium 2-benzo[1,3]dioxol-5-yl-4-(4-methoxy-phenyl)-4-oxo -3-(3,4,5-trimetho xy-benzyl)-but-2-enoate} could improve postischemic contractile dysfun ction in open-chest pigs, Myocardial stunning was achieved by a sequen ce of three 10-min left anterior descending (LAD) occlusions intersper sed with 15 min of reperfusion, All pigs received either an intravenou s saline vehicle (n = 6) or PD156707 (n = 6) at a loading dose infusio n of 10 mg/kg/h for 1 h before the first occlusion followed by a maint enance dose of 7 mg/kg/h for 4 h. Systolic wall thickening (percentage of baseline) was measured with sonomicrometers. There was no signific ant difference in systolic thickening between groups at baseline, at t he end of the final stunning occlusion, or at any of the time points d uring reperfusion. PD156707 significantly reduced arterial blood press ure before myocardial ischemia and throughout reperfusion. There was n o significant difference in size of the region at risk between groups. In conclusion, selective blockade of ETA receptors with PD156707 did not significantly alter postischemic contractile function in open-ches t pigs. These results suggest that activation of ETA receptors by endo genous ET does not play a significant role in the pathogenesis of myoc ardial stunning.