The effect of FR167653 in a canine total hepatic vascular exclusion model.
OBJECTIVE
Though liver grafts from non-heart-beating donors are now attracting much attention, these grafts inevitably suffer from severe warm ischemia. The aim of this study was to evaluate the effect of TNF-alpha and IL-1 suppression on warm ischemia-reperfusion injury in a canine total hepatic vascular exclusion model.


METHODS
Warm ischemia was induced by 1-h total hepatic vascular exclusion with active splenofemuro-juglar bypass. Animals were divided into two groups. FR167653 (1 mg/kg/hr) was administered via the portal vein from 30 min prior to ischemia until 2 h after reperfusion to the FR group (n = 7), and a vehicle was administered to the control group (n = 7). The serum alanine aminotransferase, aspartate amino-transferase, lactate dehydrogenase, and hyaluronic acid levels were measured. Hepatic tissue blood flow was also measured. Liver specimens were harvested for histological study, and polymorphonuclear neutrophils were counted.


RESULTS
Serum liver enzymes were significantly (p < 0.05) lower, and hepatic tissue blood flow was kept significantly (p < 0.05) better in the FR group than in the control. Histological tissue damage was mild, and polymorphonuclear neutrophil infiltration was significantly (p < 0.05) lower in the FR group than in the control group.


CONCLUSIONS
FR167653 provides protective effects on hepatic warm ischemic injury in a canine total hepatic vascular exclusion model.
Sunose
Yutaka
Y
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
Takeyoshi
Izumi
I
Tsutsumi
Hirofumi
H
Kawata
Kiyoshi
K
Iwazaki
Shigeru
S
Matsumoto
Koshi
K
Ohwada
Susumu
S
Morishita
Yasuo
Y
D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D006504:Hepatic Veno-Occlusive Disease / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008102:Liver Circulation / Q000187:drug effects; D016031:Liver Transplantation / Q000009:adverse effects*; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D012720:Severity of Illness Index; D013997:Time Factors
C104334:FR 167653; D007166:Immunosuppressive Agents; D011720:Pyrazoles; D011725:Pyridines