Effects of endothelin receptor antagonist TAK-044 on small bowel autograft from a controlled non-heart-beating donor model.
BACKGROUND
This study investigated the possibility of pharmacologic protection using an endothelin (ET) receptor antagonist, TAK-044 (TAK), for small bowel autograft in a canine controlled non-heart-beating donor (NHBD) model.


METHODS
Sixteen adult mongrel dogs were allocated into 2 groups. TAK (3 mg/kg) (n = 8) was administered intravenously 30 minutes before ischemia and 30 minutes before graft reperfusion. Vehicle was administered in the control (n = 8). The superior mesenteric artery and vein were clamped for 90 minutes to induce warm ischemia as a controlled NHBD model. The entire small bowel then was harvested and stored in 4 degrees C University of Wisconsin solution for 4 hours. The autograft was transplanted orthotopically. Mucosal tissue blood flow, intramucosal pH (pHi), and serum ET-1 levels were measured. Specimens were evaluated histopathologically and ET-1 immunohistochemically.


RESULTS
TAK provided significantly higher tissue blood flow and pHi at 3 and 6 hours after graft reperfusion and significantly higher serum ET-1 levels at 1 hour after graft reperfusion as compared with the control group. TAK had histopathologic tissue damage graded as superficial, did not reach to grade 5 on Park's grading as in controls, and provided less intense immunoreactivity for ET-1 immunohistochemical staining.


CONCLUSIONS
TAK may have clinical application in small bowel transplantation from controlled NHBD or conditions related to ischemia-reperfusion (I/R) injury.
Sunose
Y
Y
Second Department of Surgery, Gunma University Faculty of Medicine, Maebashi, Japan.
Ohwada
S
S
Takeyoshi
I
I
Matsumoto
K
K
Tsutsumi
H
H
Tomizawa
N
N
Kawate
S
S
Morishita
Y
Y
D000818:Animals; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000098:blood supply / Q000473:pathology / Q000637:transplantation*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000517:prevention & control; D014182:Transplantation, Autologous
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; C088196:TAK 044