Preoperative bombesin administration can protect the rat small bowel allograft from ischemic reperfusion injury.
OBJECTIVE
Ischemic reperfusion injury (IR/I) should be minimum for the success of small bowel transplantation (SBTx). This study investigated whether preoperative administration of neuropeptide bombesin (BBS) had a protective effect against IR/I and subsequent acute rejection.


METHODS
Allogenic SBTx was performed heterotopically in rats (n = 18). All rats were administered FK506 (0.32 mg/kg per day) everyday. The rats were divided into 3 groups of 6 rats each: group 1, BBS(-)5: warm ischemic time (WIT), 5 minutes without BBS; group 2, BBS(-)15: WIT, 15 minutes without BBS; group 3, BBS(+)15: WIT, 15 minutes with BBS. The specimens were obtained from the stoma site at 1 hour after reperfusion and on postoperative day (POD) 1 and 7. The graft mucosal state and degree of acute rejection were evaluated by H&E staining. The apoptotic cells in the crypt lesion was evaluated using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling immunohistochemistry. Apoptotic index (AI) was calculated for quantitative analysis.


RESULTS
H&E staining revealed that the mucosal villi on POD 1 remained shortened in the BBS(-)15 group than in the other two groups. One hour after reperfusion, the AI in the BBS(-)15 group was 145.0 per thousand +/- 37.2 per thousand, which was significantly higher (P < .05) than in the BBS(-)5 group (32.6 per thousand +/- 5.0 per thousand) or the BBS(+)15 group (32.0 per thousand +/- 3.0 per thousand). On POD 7, the AI in the BBS(-)15 group was 63.7 per thousand +/- 5.03 per thousand, which was significantly higher (P < .05) than in the BBS(-)5 (17.3 per thousand +/- 4.6 per thousand) or the BBS(+)15 group (12.3 per thousand +/- 3.06 per thousand).


CONCLUSIONS
Even a short WIT of 15 minutes induced considerable allograft mucosal damage, which also worsened acute rejection. Exogenous BBS could prevent mucosal damage by IR/I and was also beneficial for the prevention of acute rejection.
Kinoshita
Hiromi
H
Division of Surgery, Children's Research Hospital, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-0841, Japan.
Kimura
Osamu
O
Furukawa
Taizo
T
Higuchi
Koji
K
Chujo
Satoru
S
Iwai
Naomi
N
D000818:Animals; D017209:Apoptosis; D001839:Bombesin / Q000494:pharmacology*; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000637:transplantation*; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011300:Preoperative Care; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*
D018377:Neurotransmitter Agents; D001839:Bombesin