Masakazu Segawa

Effect of a platelet activating factor antagonist (CV6209) on shock caused by temporary hepatic inflow occlusion.

Platelet activating factor (PAF) is a newly discovered inflammatory chemical mediator, which was reported to play a pivotal role in various types of shock. There is also a great possibility that PAF plays an important role in the shock caused by hepatic inflow occlusion. In the present study, the effect of CV6209, a PAF antagonist, on the shock caused by the occlusion was investigated. Intravenous 3 micrograms/kg of PAF caused hypotension in Wistar rats (n=6), and pretreatment with intravenous 3 mg/kg of CV6209 significantly (p less than 0.01) prevented the hypotension (n=6). Forty-five minutes of hepatic inflow occlusion caused hypotension in rats during the occlusion period, and the hypotension continued even after restoration of blood flow in control group (pretreated with saline i.v. only, n=5). In contrast, this hypotension was significantly (p less than 0.01) reversed in PAF antagonist group (pretreated with 3 mg/kg of CV6209 i.v., n=5). In sham-operated rats (n=6), arterial pressure remained unchanged and not hypotensive during the monitoring period. The survival rate of rats 90 minutes after declamp was 30% in control group (n=20), and that was significantly (p less than 0.05) improved to be 65% in PAF antagonist group (n=20). In conclusion, PAF plays an important role in the shock and death caused by temporary hepatic inflow occlusion, and a PAF antagonist could be a therapeutic drug against temporary hepatic inflow occlusion.

Initial hepatic metabolic function in canine liver and pancreas cluster transplantation.

In this study, initial hepatic metabolic function was evaluated by determining the arterial ketone body ratio (AKBR) and plasma amino acid concentrations in an experimental orthotopic combined hepatopancreatic transplantation (OHPT), and comparing the same values in orthotopic liver transplantation (OLT). In OHPT, AKBR decreased in the anhepatic phase and recovered to the preoperative value just 1 h after reperfusion. On the other hand, in OLT, the recovery of AKBR took 3 h after reperfusion with a significant difference compared to OHPT (P<0.05). Plasma amino acid levels, especially alanine and total free plasma amino acids increased in the anhepatic phase and recovered within 1 h of reperfusion in OHPT. However, they did not recover until 3 h after reperfusion in OLT. This rapid recovery of hepatic metabolic function in OHPT should be attributed to the order of reperfusion in which the reconstruction of arterial blood flow precedes that of portal blood flow. This model is useful for assessing the best way by which the grafted liver can control the timing, order, rate, and volume of blood that should be released.

Focal nodular hyperplasia of the liver

We present herein two successfully treated cases of focal nodular hyperplasia (FNH) of the liver, a relatively rare disease. Case 1 was a 3 year old child in whom typical FNH developed in the left lateral segment of the liver, whereas Case 2 was a 22 year old man in whom characteristic findings were lacking on preoperative diagnostic imaging. Scintigraphy was not performed in either case, however, postoperative histological examination confirmed FNH. Thus, in patients with a hypervascular tumor and normal liver function, FNH should be strongly suspected and a series of scintigraphy proposed. Both cases showed a negative association with oral contraceptive intake but no other obvious etiology was suggested.

The immunosuppressive effect of hepatocytes in rats : assessment by heart allograft survival and delayed-type-hypersensitivity reactions

The immunosuppressive effect of hepatocytes was examined experimentally by heart allograft and delayed-type-hypersensitivity (DTH) reactions. The hepatocyte inoculation (1×107) of BDE (of the major histocompatibility complex haplotype RT1u), LEW (RT11), and DA (RT1a) into the spleens of LEW rats significantly prolonged the survival of BDE heart allografts to 14.3±2.7 (mean±SD), 9.2±0.8, and 10.8±2.3 days respectively, compared with 6.7±0.8 days in controls (p<0.01). Moreover, the BDE hepatocytes had a significantly prolonged survival compared to the LEW (p<0.01) and DA (0.02<p<0.05) groups. BDE hepatocyte (donor specific) inoculation 4 and 7 days before priming with the spleen cells reduced DTH responses in the LEW rats to 44.6±4.8 per cent, and 74.2±8.0 per cent, respectively. DA hepatocyte inoculation (third party) 4 and 7 days prior to priming reduced DTH responses to 72.5±11.5 per cent, and 76.5±11.9 per cent, respectively. All DTH responses were significantly suppressed after hepatocyte inoculation compared to 100 per cent in the controls (p<0.01). Moreover, the inoculation of BDE hepatocytes (donor specific) 4 days prior to the priming significantly reduced DTH responses compared to the group primed 7 days before (p<0.01). From these results we concluded that hepatocytes produced not only non-specific but also donor specific immunosuppressive effects through T cell immune reaction. Moreover, donor specific immunosuppressive effects were induced at least 4 to 7 days after hepatocyte inoculation.