Effect of FR167653 on pancreatic ischemia-reperfusion injury in dogs.
BACKGROUND
The role of inflammatory cytokines is still unclear in ischemia-reperfusion injury of the pancreas. We investigated the effect of FR167653 (FR), a newly developed compound that is a potent suppressor of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha on ischemia-reperfusion injury of the isolated pancreatic tail in dogs.


METHODS
The tail of the pancreas was subjected to ischemia for 90 minutes. During occlusion of the vascular inflow, the head of the pancreas was removed. A control group (n = 14) and an FR treatment group (n = 11) were evaluated for survival rate, tissue blood flow, arterial oxygen pressure (Pao(2)), serum amylase and lipase levels, glucose and insulin, liver enzymes, creatinine, IL-1beta mRNA in the peripheral blood, and histopathology.


RESULTS
Six of the 14 control animals and 2 of the 11 FR-treated animals died. The FR treatment group showed lower amylase (P=.037) and lipase (P =.030) levels, lower IL-1beta mRNA expression (P =.033), and less pancreatic tissue damage (P =.041) than did the control group, but there was no remarkable change in endocrine function (P =.422). Pao(2) during the acute phase in the FR treatment group was maintained (P=.009), but pulmonary tissue was damaged. Results of biochemical and histologic examinations of the liver and kidneys were unremarkable.


CONCLUSIONS
FR ameliorates ischemia-reperfusion injury of the pancreas and reduces the production of inflammatory cytokines that may contribute to secondary damage to distant organs.
Department of Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
H
H
Yamamoto
A
A
Sugitani
H
H
Kitada
T
T
Arima
Nishiyama Ki
K
K
Motoyama
M
M
Shiiba
R
R
Kawano
T
T
Morisaki
Y
Y
Nakafusa
M
M
Tanaka
D000818:Animals; D004285:Dogs; D005260:Female; D007375:Interleukin-1 / Q000097:blood; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology*; D007515:Islets of Langerhans / Q000503:physiopathology; D008297:Male; D010179:Pancreas / Q000098:blood supply* / Q000503:physiopathology; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology*
C104334:FR 167653; D007375:Interleukin-1; D011720:Pyrazoles; D011725:Pyridines