Role of endogenous endothelin on coronary reflow after cardioplegic arrest.
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.
Goodwin
A T
AT
Department of Cardiac Surgery, Royal Brompton and Harefield NHS Trust, Heart Science Centre, Harefield Hospital, Middlesex, United Kingdom.
Smolenski
R T
RT
Gray
C C
CC
Jayakumar
J
J
Amrani
M
M
Yacoub
M H
MH
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
D004149:Dioxoles; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; C093322:PD 155080; D011725:Pyridines; D013449:Sulfonamides; D013777:Tetrazoles; C120582:tezosentan; D000077300:Bosentan