Endothelin-A receptor antagonist BQ123 protects against myocardial and endothelial reperfusion injury.
BACKGROUND
This study was designed to investigate the effects of the selective endothelin-A receptor antagonist BQ123 on myocardial and endothelial function after reversible deep hypothermic ischemia and reperfusion.


METHODS
Isogenic intra-abdominal heterotopic heart transplantation was performed in Lewis rats. After one hour of cold ischemic preservation reperfusion was started after application of either saline vehicle or BQ123 (1 micromol/L). Left-ventricular pressure-volume relations and myocardial blood flow were assessed after one and 24 hours of reperfusion. Responses to endothelium-dependent vasodilator acetylcholine and endothelium-independent vasodilator sodium nitroprusside were also determined.


RESULTS
BQ123 significantly improved myocardial contractility, as indicated by the leftward shift of the systolic pressure-volume relation and significantly increased 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 higher in the BQ123 group (p < 0.05).


CONCLUSIONS
These results suggest that endothelin-A receptor antagonists may be useful in reducing ischemia/reperfusion injury after heart transplantation by preservation of myocardial and endothelial function.
Department of Cardiac Surgery, University of Heidelberg, Germany.
G
G
Szabó
S
S
Bährle
L
L
Fazekas
D
D
MacDonald
N
N
Stumpf
C F
CF
Vahl
S
S
Hagl
D000818:Animals; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced; D016027:Heart Transplantation; D007036:Hypothermia, Induced; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous; D016277:Ventricular Function, Left / Q000187:drug effects*
D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)