ENDOTHELIN-A RECEPTOR ANTAGONIST BQ123 PROTECTS AGAINST MYOCARDIAL AND ENDOTHELIAL REPERFUSION INJURY

Background: This study was designed to investigate the effects of the selective endothelin-A receptor antagonist BQ123 on myocardial and end othelial function after reversible deep hypothermic ischemia and reper fusion. Methods: Isogenic intra-abdominal heterotopic heart transplant ation was performed in Lewis rats. After one hour of cold ischemic pre servation reperfusion was started after application of either saline v ehicle or BQ123 (1 mu mol/L). Left-ventricular pressure-volume relatio ns and myocardial blood flow were assessed after one and 24 hours of r eperfusion. Responses to endothelium-dependent vasodilator acetylcholi ne and endothelium-independent vasodilator sodium nitroprusside were a lso determined, Results: BQ123 significantly improved myocardial contr actility, as indicated by the leftward shift of the systolic pressure- volume relation and significantly increased myocardial blood flow duri ng early reperfusion (p < 0.05). Although myocardial function and base line myocardial blood flow were similar in both groups after 24 hours of reperfusion, endothelium-dependent vasodilatation was still signifi cantly higher in the BQ123 group (p(0.05). Conclusions: These results suggest that endothelin-A receptor antagonists may be useful in reduci ng ischemia/reperfusion injury after heart transplantation by preserva tion of myocardial and endothelial function.