Ischemia-reperfusion injury at the microvascular level - Treatment by endothelin A-selective antagonist and evaluation by myocardial contrast echocardiography

Background-The purpose of this study was to verify whether endothelin A-ant agonist administration at the time of coronary reperfusion preserves postis chemic microvasculature and whether myocardial contrast echo (MCE) is able to detect pharmacologically induced changes in microvascular reflow. Methods and Results-Twenty dogs underwent 90 minutes of LAD occlusion (OCC) followed by 180 minutes of reperfusion (RP). Five minutes before LAD reope ning, an intravenous bolus (5 mg/kg) of LU 135252 was given in 10 dogs and vehicle in the remaining 10. At baseline (BSL), OCC, and 90 and 180 minutes of RP, microvascular flow (BF) was assessed by microspheres, and MCE was p erformed with intravenous echo contrast. MCE videointensity and BF were exp ressed as risk area/control ratio. Myocardial thickness of the risk area wa s calculated by 2D echo. No differences in BF between the 2 groups were obs erved at BSL, OCC, and 90 minutes of RP. At 180 minutes of RP, BF was decre ased in controls (70+/-4% of BSL; P<0.005 versus BSL) and preserved in LU 1 35252-treated animals (89+/-4% of BSL; P=NS versus BSL; P<0.05 versus contr ols). Videointensity at MCE closely followed the changes in BF observed in both groups throughout the protocol. Myocardial thickness at 180 minutes of RP increased to 138.6+/-9.9% of BSL in controls and remained at 108.9+/-7. 4% of BSL in treated dogs (P<0.05). Conclusions-Endothelin A-antagonist treatment at the time of reperfusion si gnificantly limited the progressive decrease in postischemic microvascular reflow and the increase in myocardial thickness. MCE allowed a reliable eva luation of pharmacologically induced changes in microvascular flow.