The role of endothelin-B receptors in myocardial and endothelial reperfusion injury after heart transplantation

Background: This study was designed to investigate the effects of the selec tive endothelin-B (ET-B) receptor agonist IRL1620 and the selective ET-B re ceptor antagonist BQ788 on myocardial and endothelial function after revers ible deep hypothermic ischemia and reperfusion. Methods: Isogenic intraabdo minal heterotopic heart transplantation was performed on Lewis rats. After one hour of cold ischemic preservation, reperfusion was started either afte r application of saline vehicle or IRL1620 or BQ788 or both. Left Ventricul ar pressure-volume relations and myocardial blood flow were assessed after one and 24 hours of reperfusion. Endothelium-dependent vasodilatation to ac etylcholine (ACH) and endothelium-independent vasodilatation to sodium nitr oprusside (SNP) were also determined. Results: IRL1620 attenuated and BQ788 improved myocardial contractility significantly as indicated by the left o r upward shift of the systolic pressure-volume relation, respectively, and significantly changed myocardial blood flow during early reperfusion (p<0.0 5). Although myocardial function and baseline myocardial blood flow were si milar in both groups after 24 hours of reperfusion, endothelium-dependent v asodilatation was still significantly lower in the IRL1620 and higher in th e BQ788 group (p<0.05). Conclusions: These results suggest that activation of the ET-B receptors contributes to reperfusion injury after cardiac prese rvation in a rat heart transplant model.