Abstract
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°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. (Surgery 2001;130:819-25.)
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Article info
Publication history
Accepted:
April 18,
2001
Footnotes
*Reprint requests: Susumu Ohwada, MD, Second Department of Surgery, Gunma University Faculty of Medicine, 3-39-15 Showa-Machi, Maebashi, 371-8511, Japan.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
