The endothelin-1 receptor antagonist BQ-123 reduces infarct size in a canine model of coronary occlusion and reperfusion.
OBJECTIVE
The aim was to determine the effect of the endothelin-1 receptor antagonist, BQ-123, on infarct size in anaesthetised dogs subjected to 90 min of left circumflex coronary artery occlusion and 5 h of reperfusion.


METHODS
BQ-123 was given directly into the left circumflex coronary artery at 0.03 or 10 micrograms.kg-1 x min-1 starting 15 min before coronary occlusion and continuing throughout occlusion and reperfusion. Regional myocardial blood flow was determined before, during, and after ischaemia. At the end of the study, infarct size was determined using triphenyltetrazolium chloride staining.


RESULTS
Myocardial infarct size was significantly reduced by BQ-123 (40% reduction from vehicle infarct size) at both doses used. This cardioprotection occurred despite 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 found to completely abolish the coronary constrictor effect of intracoronary endothelin-1 administration.


CONCLUSIONS
These data indicate that endothelin-1 release during ischaemia may be involved in the pathogenesis of myocardial ischaemia and infarction.
Grover
G J
GJ
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
Dzwonczyk
S
S
Parham
C S
CS
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004334:Drug Administration Schedule; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000627:therapeutic use
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)