THE ENDOTHELIN-1 RECEPTOR ANTAGONIST BQ-123 REDUCES INFARCT SIZE IN ACANINE MODEL OF CORONARY-OCCLUSION AND REPERFUSION

Objective: The aim was to determine the effect of the endothelin-1 rec eptor antagonist, BQ-123, on infarct size in anaesthetised dogs subjec ted to 90 min of left circumflex coronary artery occlusion and 5 h of reperfusion. Methods: BQ-123 was given directly into the left circumfl ex coronary artery at 0.03 or 10 mug.kg-1.min-1 starting 15 min before coronary occlusion and continuing throughout occlusion and reperfusio n. Regional myocardial blood flow was determined before, during, and a fter ischaemia. At the end of the study, infarct size was determined u sing triphenyltetrazolium chloride staining. Results: Myocardial infar ct size was significantly reduced by BQ-123 (40% reduction from vehicl e infarct size) at both doses used. This cardioprotection occurred des pite a lack of effect of BQ-123 on peripheral haemodynamic status. BQ- 123 also had no effect on regional myocardial blood flow in ischaemic and non-ischaemic tissue. Both cardioprotective doses of BQ-123 were f ound to completely abolish the coronary constrictor effect of intracor onary endothelin-1 administration. Conclusions: These data indicate th at endothelin-1 release during ischaemia may be involved in the pathog enesis of myocardial ischaemia and infarction.