Effects of endothelin receptor antagonist TAK-044 on small bowel autograftfrom a controlled non-heart-beating donor model

Background. This study investigated the possibility of pharmacologic protec tion using an endothelin (ET) receptor antagonist, TAK-044 (TAK), for small bowel autograft in a canine controlled non-heartbeating 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 contro l (n = 8). The superior mesenteric artery and vein were clamped for 90 minu tes to induce warm ischemia as a controlled NHBD model. The entire small bo wel then was harvested and stored in 4 degreesC University, of Wisconsin so lution for 4 hours. The autograft was transplanted ortho-topically. Mucosal tissue bloodflow, intramucosal pH (pHi), and serum ET-1 levels were measur ed. Specimens were evaluated histopathologically and ET-1 immunohislochemic ally. Results. TAK provided significantly higher tissue bloodflow and pHi at 3 an d 6 hours after graft reperfusion and significantly higher serum ET-1 level s 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 Parks grading as in controls, and provided less intense im immun oreactivity ET-1 immunohistochemical staining. Conclusions. TAK may have clinical application in small bowel transplantati on from controlled NHBD or conditions related to ischemia-reperfusion (I/R) injury.