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Updated: Oct 3, 2026
An Immunological Model for Heterotopic Heart and Cardiac Muscle Cell Transplantation in Rats
Published on: May 8, 2020
Effects of endothelin receptor antagonist TAK-044 on small bowel autograft from a controlled non-heart-beating donor
Y Sunose1, S Ohwada, I Takeyoshi
1Second Department of Surgery, Gunma University Faculty of Medicine, Maebashi, Japan.
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.
