| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1994: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Experimental study of liver injury after partial hepatectomy with intermittent or continuous hepatic vascular occlusion : In normal and cirrhotic liver, rats, the total duration of clamping was 60 min and the liver damage following 3 ischemic modality were compared : a 15-min intermittent clamping group (Group I), a 30-min intermittent clamping group (Group II), and a 60-min continuous clamping group (Group III). The intracellular calcium concentration and hepatic enzyme were lowest in Group I.The recovery of ATP,energy charge and maintenance of phosphory lative efficiency of mitochondria was satisfactory in Group I,II in normal liver and Group I in cirrhotic liver. Therefore, when performing resection of a cirrhotic liver, a 15-min intermittent clamping should be adopted. On the other hand, calcium antagonist (Verapamil hydrochloride) revealed protective effect against ischemic liver injury.
Liver cell damage induced by experimental endotoxemia in rats and protective effect of the calc
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ium antagonist : Experimental liver injury was induced by the continuous intravenous administration of lipopolys accharide (LPS,L-group) in rats, and diltiazem was also injected simultaneously with LPS (LD-group). The involvement of Kupffer cells in LPS induced liver injury was assessed in rats pretreated with Gadolinium chloride (GdC13). In the L-group, the level of calcium concentration in the mitochondria was elevated, then that in cytoplasm was elevated. The level of calcium concentration of cytoplasm and mitochondria was reduced significantly in the LD-group. The elevation of serum liver enzymes and decrease of mitochondrial function were significantly inhibited in the Ld-Group. There were no differences of serum purine nucleoside phosphorylase (PNP) activity between the L and LD groups. On the other hand, the elevation of serum PNP activity and liver enzymes were significantly inhibited by GdC13 pretreatment. These results suggest that the Kupffer cells, activated by LPS,injured sinusoidal endothelial cells, and the damage of hepatocytes progressed. Diltiazem protected the hepatocytes during experimental endotoxemia by inhibiting elevation of calcium concentration in the cytoplasm and mitochondria. Diltiazem did not, however, appear to protect the endothelial cells. Less
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