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 selective endothelin-B (ET-B) receptor agonist IRL1620 and the selective ET-B receptor antagonist BQ788 on myocardial and endothelial function after reversible deep hypothermic ischemia and reperfusion.


METHODS
Isogenic intraabdominal heterotopic heart transplantation was performed on Lewis rats. After one hour of cold ischemic preservation, reperfusion was started either after application of saline vehicle or IRL1620 or BQ788 or both. Left ventricular pressure-volume relations and myocardial blood flow were assessed after one and 24 hours of reperfusion. Endothelium-dependent vasodilatation to acetylcholine (ACH) and endothelium-independent vasodilatation to sodium nitroprusside (SNP) were also determined.


RESULTS
IRL1620 attenuated and BQ788 improved myocardial contractility significantly as indicated by the left or upward shift of the systolic pressure-volume relation, respectively, and significantly changed myocardial blood flow during early reperfusion (p<0.05). Although myocardial function and baseline myocardial blood flow were similar in both groups after 24 hours of reperfusion, endothelium-dependent vasodilatation was still significantly lower in the IRL1620 and higher in the BQ788 group (p<0.05).


CONCLUSIONS
These results suggest that activation of the ET-B receptors contributes to reperfusion injury after cardiac preservation in a rat heart transplant model.
Szabó
G
G
Department of Cardiac Surgery, University of Heidelberg, Germany. dzsi@hotmail.com
Bährle
S
S
Fazekas
L
L
Vahl
C F
CF
Hagl
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000819:agonists; D004730:Endothelium, Vascular / Q000293:injuries*; D006339:Heart Rate / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects*; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000209:etiology*; D009599:Nitroprusside / Q000494:pharmacology; D009842:Oligopeptides / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000819:agonists; D010880:Piperidines / Q000037:antagonists & inhibitors; D051381:Rats; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists / Q000502:physiology*; D020127:Recovery of Function / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D015424:Reperfusion / Q000009:adverse effects*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010880:Piperidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014665:Vasodilator Agents; C074308:sovateltide; D009599:Nitroprusside; C086539:BQ 788; D000109:Acetylcholine