Elsevier

Journal of Pediatric Surgery

Volume 40, Issue 12, December 2005, Pages 1877-1880
Journal of Pediatric Surgery

Preoperative bombesin administration can protect the rat small bowel allograft from ischemic reperfusion injury

https://doi.org/10.1016/j.jpedsurg.2005.08.035Get rights and content

Abstract

Background/Purpose

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‰ ± 37.2‰, which was significantly higher (P < .05) than in the BBS(−)5 group (32.6‰ ± 5.0‰) or the BBS(+)15 group (32.0‰ ± 3.0‰). On POD 7, the AI in the BBS(−)15 group was 63.7‰ ± 5.03‰, which was significantly higher (P < .05) than in the BBS(−)5 (17.3‰ ± 4.6‰) or the BBS(+)15 group (12.3‰ ± 3.06‰).

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.

Section snippets

Animals

Eighteen male Brown Norway rats weighing 350 to 400 g were used as transplant donors and 18 male Lewis rats weighing 250 to 300 g were used as recipients. Rats were fasted for 6 hours with water ad lib before surgery. This experimental procedure was permitted by the Committee for Animal Research, Kyoto Prefectural University of Medicine.

Experiment design

Allogeneic SBTx was performed heterotopically in rats (n = 18). The donor operation was performed with a procedure modified from the report by Monchik and

Histological findings

In H&E staining, 1 hour after reperfusion, the villi and crypt epithelial cells of the grafts were damaged with no significant difference among the 3 groups. On the other hand, on POD 1, the villous height in the BBS(−)15 group remained shortened and the mucosal damage seen 1 hour after reperfusion seemed to be continued, whereas the villi in the BBS(−)5 group and in the BBS(+)15 group could regenerate better compared with BBS(−)15 group. The length of the crypt lesion was almost the same among

Discussion

The present study demonstrated that even 15 minutes of WIT induced mucosal damage from IR/I. In addition, it was found that such damage worsened acute rejection, and neuropeptide BBS could reduce such damage and could also reduce the degree of acute rejection.

It was reported [1] that the longer the ischemic time, the more damage the small bowel allograft suffered. There have been some studies [4], [6] concerning IR/I in the small bowel of rats. However, the present study is the first to report

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  • Prenatal administration of neuropeptide bombesin promotes lung development in a rat model of nitrofen-induced congenital diaphragmatic hernia

    2014, Journal of Pediatric Surgery
    Citation Excerpt :

    Our results showed BBS was considered to have promoted fetal lung maturity. As described previously, we investigated the effects of the BBS and elucidated its multipotent ability to maintain and modulate the mucosal structure and immunity of the gastrointestinal system [6–10]. Based on present and previous data, we speculate that BBS plays an important role via the same pathways in the respiratory and intestinal mucosa systems.

  • Bombesin can minimize impairments of interstitial cells of Cajal induced by FK506 in small bowel transplantation

    2009, Journal of Pediatric Surgery
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    Its actions in the intestine involve the regulation of gut motility, the modulation of gastrointestinal enteropancreatic hormone release, and the stimulation of intestinal epithelial growth. Previously, we reported that BBS also had a trophic effect on the reconstruction of allograft mucosa by stimulating the proliferation of mucosal crypt cells [7], an immunosuppressing effect against acute rejection [8], and a suppressing effect against ischemic reperfusion (I/R) injury in SBTx [9]. In addition, we reported that BBS could preserve graft enteric ganglia against FK506 neurotoxicity [10].

  • Reply

    2007, Journal of Pediatric Surgery

Presented at the 38th Annual Meeting of the Pacific Association of Pediatric Surgeons, May 22-26, 2005, Vancouver, Canada.

This work was supported by grants-in-aid (16659482) for scientific research from the Ministry of Education, Science and Culture of Japan.

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