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

Abstract

The purpose of this study was to verify whether endothelin A-antagonist administration at the time of coronary reperfusion preserves postischemic microvasculature and whether myocardial contrast echo (MCE) is able to detect pharmacologically induced changes in microvascular reflow. Twenty dogs underwent 90 minutes of LAD occlusion (OCC) followed by 180 minutes of reperfusion (RP). Five minutes before LAD reopening, 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 performed with intravenous echo contrast. MCE videointensity and BF were expressed as risk area/control ratio. Myocardial thickness of the risk area was calculated by 2D echo. No differences in BF between the 2 groups were observed at BSL, OCC, and 90 minutes of RP. At 180 minutes of RP, BF was decreased in controls (70+/-7.4% of BSL; P:<0.005 versus BSL) and preserved in LU 135252-treated animals (89+/-4% of BSL; P=NS versus BSL; P<0.05 versus controls). 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). Endothelin A-antagonist treatment at the time of reperfusion significantly limited the progressive decrease in postischemic microvascular reflow and the increase in myocardial thickness. MCE allowed a reliable evaluation of pharmacologically induced changes in microvascular flow.