INTRAVENOUS ADMINISTRATION OF THE ENDOTHELIN-1 ANTAGONIST BQ-123 DOESNOT AMELIORATE MYOCARDIAL ISCHEMIC-INJURY FOLLOWING ACUTE CORONARY-ARTERY OCCLUSION IN THE DOG

Objective: It has been proposed that myocardial ischaemic injury is mo dulated in part by the release of endothelin-1 from the coronary endot helium either during ischaemia or following reperfusion. Release of su fficient amounts of endothelin-1 would result in coronary vasoconstric tion and could potentiate ischaemic damage. An endothelin-1 antagonist , BQ-123, was given intravenously to evaluate the role of endothelin-1 in postischaemic injury and determine whether blockade of the ET(A) r eceptor would afford protection from ischaemia/reperfusion injury. Met hods: Myocardial injury was induced in anaesthetised dogs using 90 min of left circumflex coronary artery occlusion followed by 4 h of reper fusion. Animals treated with a continuous intravenous infusion of BQ-1 23 (0.1 mg.kg(-1).min(-1)), begun 10 min before ischaemia and continue d throughout ischaemia and reperfusion. were compared to saline treate d animals. Results: After 4 h of reperfusion the myocardial infarct si ze measured by triphenyltetrazolium chloride staining was not differen t between the two groups. Infarct size in the control group was 25.7(S EM 5.4)% of the area at risk while BQ-123 treatment resulted in an inf arct size of 29.2(7.1)% of the area at risk (p = 0.70). Plasma endothe lin-1 concentration measured at the coronary sinus was only significan tly increased following 5 min of reperfusion. Conclusions: The intrave nous administration of a specific ET(A) receptor antagonist does not p rotect against ischaemia/reperfusion injury. These results suggest tha t endothelin-1 receptor antagonists require access to the area at risk during occlusion to protect the myocardium from ischaemic injury.