title: Role of endogenous endothelin on coronary reflow after cardioplegic arrest.
abstract: OBJECTIVE
  Endothelin plays a role in the regulation of basal coronary tone. We hypothesized that low coronary reflow and reduced cardiac function after prolonged ischemia may be due to increased release of endogenous endothelin.
  
  
  METHODS
  Using an isolated perfused rat heart, we examined the effect of the addition of various endothelin antagonists during reperfusion after 4 hours of cardioplegic arrest at 4 degrees C. Hearts were freeze-clamped at the end of reperfusion for analysis of high-energy phosphate levels. Results are expressed as the percentages of preischemic values.
  
  
  RESULTS
  The addition of bosentan or Ro61-0612 (nonselective endothelin antagonists) resulted in a significant increase in the recovery of coronary flow after 30 minutes of reperfusion (100.9% vs 85.3% [P =.03] and 122.4% vs 83.7% [P <.001], respectively, versus controls). The addition of PD155080 (endothelin A antagonist) had a similar effect (129.5% vs 91.4%, P =.008). BQ788 (endothelin B antagonist) and phosphoramidon (endothelin-converting enzyme inhibitor) had no effect. Myocardial adenosine triphosphate levels were significantly (12.1%) higher after reperfusion with Ro61-0612 (18.1 +/- 0.4 micromol/g vs 16.2 +/- 0.5 micromol/g, P =.01). There was no difference in the recovery of cardiac mechanical function with any of the antagonists studied.
  
  
  CONCLUSIONS
  These results suggest that endogenous endothelin plays a role in low coronary reflow after prolonged cardioplegic arrest but does not impair recovery of myocardial function.
authors.affiliation: Department of Cardiac Surgery, Royal Brompton and Harefield NHS Trust, Heart Science Centre, Harefield Hospital, Middlesex, United Kingdom.
authors.forename: A T
authors.initials: AT
authors.lastname: Goodwin
authors.forename: R T
authors.initials: RT
authors.lastname: Smolenski
authors.forename: C C
authors.initials: CC
authors.lastname: Gray
authors.forename: J
authors.initials: J
authors.lastname: Jayakumar
authors.forename: M
authors.initials: M
authors.lastname: Amrani
authors.forename: M H
authors.initials: MH
authors.lastname: Yacoub
mesh_terms: D000818:Animals; D000077300:Bosentan; D002851:Chromatography, High Pressure Liquid; D003326:Coronary Circulation / Q000502:physiology*; D004149:Dioxoles / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006324:Heart Arrest, Induced; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D010477:Perfusion; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D004149:Dioxoles; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; C093322:PD 155080; D011725:Pyridines; D013449:Sulfonamides; D013777:Tetrazoles; C120582:tezosentan; D000077300:Bosentan