Prevention of warm ischemic injury by neuropeptide bombesin in small bowel transplantation.
OBJECTIVE
This study investigated whether preoperative administration of neuropeptide bombesin (BBS) had a protective effect against IR/I and subsequent acute rejection.


METHODS
Allogeneic SBTx was performed heterotopically in rats (n = 18). That were administered FK506 (0.32 kg/d) daily. The rats were divided into three groups of six 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 days (PODs) 1 and 7. The graft mucosal state and degree of acute rejection were evaluated by H and E staining. The apoptotic cells in the crypt lesion were evaluated using TUNEL immunohistochemistry. An apoptotic index (AI) was calculated for quantitative analysis.


RESULTS
H and E staining revealed that on POD 1 the mucosal villi were shortened in the BBS(-)15 group compared with the other two groups. One hour after reperfusion, the AI in BBS(-)15 group was 125.0 per thousand +/- 37.2 per thousand, which was significantly higher (P < .05) than that 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 heightened the possibility of acute rejection. Exogenous BBS prevented mucosal damage by IR/I and was also beneficial to prevent acute rejection.
Kimura
O
O
Division of Surgery, Children's Research Hospital, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-0841, Japan. osamu@koto.kpu-m.ac.jp
Kinoshita
H
H
Furukawa
T
T
Higuchi
K
K
Chujo
S
S
Iwai
N
N
D000818:Animals; D001839:Bombesin / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology / Q000637:transplantation*; D007511:Ischemia / Q000517:prevention & control*; D008871:Microvilli / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous / Q000473:pathology*
D001839:Bombesin