| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
The tonometric measurement of intestinal mucosa is convenient, safe, and simple. Thus, we investigated a correlation between the change of intramucosal pH (pHi) values and the histological damage of intestinal mucosa, and the efficacy ofpHi monitoring on small intestinal ischmia-reperfusion injury.
Healthy mongrel dogs of both sexes weighing 12 to 20kg were used in this study. After a laparotomy via a midline incision under general anesthesia, the small bowel was isolated with a vascular pedicle. An oral side of the jejunum and terminal ileum was cut off and the tonometer was positioned in the terminal ileum through a small enterotomy. The exerimental group was divided as follows, Group 1 ; 60-min SMA occlusion, Group 2 ; 120-min SMA occlusion, Group 3 ; 120-min both SMA and SMV occlusion, and Group 4 ; Control group with Sham operation. pHi was determined at the time of laparotomy (baseline value), during ischemia, and 1 hr after reperfusion. At the same time, biopsy specimens of the i
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leum were harvested, and mucosal injury was histopathologically graded according to Chiu's classification. We investigated a correlation between the change of pHi values from baseline and the histological damage of intestinal mucosa.
The decline of pHi from the baseline value was related to the degree of histopathological mucosal injury. In conclusion, pHi monitoring is reliable parameter to estimate graft viability after small bowel transplantation.
Ischemia-reperfusion injury has been a serious problem in small bowel transplantation. IL-1beta and TNFalpha are known to be pleiotropic cytokines associated with various inflammatory conditions such as small intestinal injury after ischemia-reperfusion. A newly synthesized organic compound, FR167653 (fujisawa Pharmaceutical Co., Ltd.Osaka) has been characterized as a potent suppressant of IL-1beta and TNFalpha production in vitro and in vivo. The effect of FR167653 on intestinal reperfusion injury was investigated in an in situ warm ischemia model of the canine gut.
Sixteen adult mongrel dogs were used. Animals were divided into two groups ; the control group (n=8) and the FR group (n=8) in which FR167653 (1mg/kg/hr) was administered continuously beginning 30min prior to the onset of ischemia and continuing for 2 hr after reperfusion. Warm ischemia was induced for 2 hr by clamping the SMA and SMV.Arterial pH,ShvO_2, and intramucosal pH (pHi) were measured. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect IL-1beta mRNA.The ilerm specimen was harvested for pathological examination. The survival rate was also investigated.
RT-PCR demonstrated that FR inhibited the expression of IL-1beta mRNA.Histological findings after 1 hr of reperfusion showed serious damage to crypt in the control group, meanwhile FR limited the damage to only mucosal surface. Seven of eight dogs in the control group died within 24 hr showing remarkable mesenteric congestion. On the contrary, six of eight dogs survived over 24 hr and three of eight dogs survived for 7 days in the FRgroup.
The survival rate, arterial pH, ShvO_2, and pHi significantly improved in the FR group compared with the control group. FR167653 appears to generate a protective effect on small bowel ischemia-reperfusion injury. Less
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