Endothelin receptor antagonist improves pulmonary hemodynamics during lung ischemia/reperfusion injury.
BACKGROUND
We have previously shown that elevated release of endothelin-1 is associated with increased pulmonary vascular resistance (PVR) immediately after reperfusion of the transplanted lung. In the present study, we investigated the effect of ET receptor blockage on pulmonary hemodynamics and function in an ex vivo lung reperfusion model after 6 hr of cold ischemia.


METHODS
Eighteen rabbits were divided into three groups: no ischemia followed by 3 hr of reperfusion (group I) and 6 hr of cold ischemia followed by 3 hr of reperfusion with either blood (group II) or blood + SB209670 (mixed ETA/ETB receptor antagonist) (group III).


RESULTS
Shortly after reperfusion, mean pulmonary artery pressure, PVR, and pulmonary edema were increased, and pulmonary compliance and PO2 were decreased in group II compared with group I. Treatment with SB209670 resulted in a significant decrease in mean pulmonary artery pressure, PVR, and pulmonary edema, and improvement in pulmonary compliance and PO2.


CONCLUSIONS
The data suggest an important role for ET-1 in lung ischemia/reperfusion injury and that the use of ET receptor antagonist immediately after transplantation may provide a new therapeutic tool in the management of early graft dysfunction.
Shennib
H
H
The Montreal General Hospital and McGill University, Québec, Canada.
Kuang
J Q
JQ
Ohlstein
E H
EH
Giaid
A
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003080:Cold Temperature; D065128:Endothelin Receptor Antagonists; D006439:Hemodynamics / Q000187:drug effects; D007189:Indans / Q000494:pharmacology*; D007511:Ischemia / Q000503:physiopathology*; D008170:Lung Compliance / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011654:Pulmonary Edema / Q000473:pathology; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D007189:Indans; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-; D010100:Oxygen