| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
The present study was designed to determine whether the duration of hepatic ischemia with or without blockade of Kupffer cell function affects reticuloendothelial phagocytic activity and tumor necrosis factor (TNF) -alpha production in the early phase of reperfusion, and to clarify the welltolerated ischemic period for the liver. Male rats were pretreated with either normal saline (NS group) or gadolinium chloride (7 mg/kg) for 2 days to inhibit Kupffer cell function (GC group) and were subjected to 30,60, or 90 minutes of total hepatic ischemia. The animals tolerated well for 30 and 60 minutes of hepatic ischemia in both groups. Although the 7-day survival rate of the NS group decreased to 28% after 90 minutes of hepatic ischemia, that of the GC group significantly improved to 68% (p<0.01). In the NS group, the plasma alanine transaminase (ALT) and TNF-alpha levels after reperfusion increased with the length of hepatic ischemia. Extremely high TNF-alpha levels (142.5(]SY.+-。[)82.4 pg/
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ml) and ALT levels (7,892(]SY.+-。[)1,817 IU/L) were observed at 1 and 6 hours after reperfusion following 90 minutes of hepatic ischemia. In the NS group, the phagocytic index (PI) after 60 minutes of reperfusion following 90 minutes of hepatic ischemia showed significant depression compared to the preischemic level and the value after 30 or 60 minutes of ischemia. The GC group had significantly lower plasma ALT and TNF-alpha levels as well as significantly less polymorphonuclear leukocyte infiltration in the liver compared to the NS group. The preischemic PI was significantly inhibited in the GC group when compared with that in the NS group, but PI in the GC group did not change significantly after reperfusion, irrespective of the ischemic time. This study demonstrated that warm ischemia of up to 60 minutes is tolerable for normal rat liver without a detrimental effect on phagocytic activity, whereas 90 minutes of hepatic ischemia causes a decrease of PI,increased TNF-alpha production, and a high mortality after reperfusion. Modulation of Kupffer cell function may have the potential to prevent reperfusion injury after hepatic ischemia, which may allow safe prolongation of the ischmic time Less
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