|Budget Amount *help
¥6,800,000 (Direct Cost : ¥6,800,000)
Fiscal Year 1991 : ¥300,000 (Direct Cost : ¥300,000)
Fiscal Year 1990 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1989 : ¥5,500,000 (Direct Cost : ¥5,500,000)
First Research : The protective effect of the immunosuppressive drug FK506 on warm ischemic injury of pig liver was studied as research of liver preservation.
Second Research : The incidence of ulcer is very high after orthotopic liver transplantation in young pigs. Therefore we studied the pathogenesis of gastric ulcer following pig liver transplantation and its prevention by vagotomy-pyloroplasty.
Third Research : To prevent rejection effectively, allograft recipients usually receive life-long immunosuppressive treatment, which may occasionally be associated with life-threatening complications. These complications of long-term immunosuppressive treatment would be avoided if it were possible to achieve a state of antigen-specific unresponsiveness that would promote a condition such tolerance we have attempted to induce such tolerance by injection of donor's spleen cells to recipients spleen at the end of operation and by administration of cyclosporin for only 7 days postoperatively.
rials and Methods
First Research : Male or female pigs weighing from 18 to 22 kg were used. Before induction of ischemic injury to the liver, side-to-side portocaval shunt and cannulation through the common bile duct were performed. Warm ischemia for 3 hours was induced by cross-clamping the portal vein and the hepatic artery at the hepatic hilus. The animals were divided into two groups : Group I pigs (n=7) served as the control, Group II (n=5) was given FK506 (1mg/kg, i. m.) for 4 days prior to being subjected to the ischemia. Survival rate, serum glutamic oxaloacetic transaminase (S-GOT), serum lactic dehydrogenase (S-LDH), hepatic transport activity of BSP, bile flow, neutrophil dependent chemiluminescence, and histologic examination of the liver were serially studied.
Second Research : Eleven orthotopic liver transplantations were performed on female young pigs weighing from 14 to 21 kg. The animals were divided into control (4 pigs) and vagotomy (7 pigs) groups. Bilateral truncal vagotomy and phyloroplasty were performed in pigs of vagotomy group. Cyclosporin (10 mg/kg, orally) was given postoperatively in the both groups. A necropsy was performed when recipient pigs died.
Third Research : To study the induction of immuno-tolerance, 5 orthotopic liver transplantations with truncal vagotomy and pyloroplasty were performed on female young pigs weighing from 19 to 20 kg. The animals were randomized into control (3 pigs) which received a 7-day postoperative course of cyclosporin (10 mg/kg, orally) and the experimental group which received the injection of donor's spleen cells (2^*10^9) to the recipient spleen via the splenic artery at the end of operation and a 7-day postoperative course of cyclosporin.
First Research : Six of 7 animals in Group I (control) died within 7 days. In contrast, all of the 5 pigs in Group II survived more than 7 days. Hepatic transport activity of BSP and bile flow were improved in Group II. The chemiluminescence of blood samples from Group I increased markedly after reperfusion. In contrast, marked increase of the chemiluminescence of blood from Group II was not observed. Vacuolar degeneration of the hepatic cells and dilatation of the sinusoid in Group I were revealed histologically, similar histological changes of the liver in Group II, however, were slight.
Second Research : In the control pigs which did not have vagotomy-pyloroplasty, the incidence of the ulcer was 100%. The ulcers involved the cardia-lesser curvature massively and all four animals died of massive gastrointestinal bleeding. In the vagotomy group, gastric ulcer was not observed. One pig is still alive one year after operation. The others died of ileus (two pigs, survived in days 5 and 28), liver necrosis (one pig, 3 days), suppurative cholangitis (2 pigs, in day 34 and 84), accidental bleeding due to falling out from arterial cannulation (one pig, 3 days). Vagotomy-pyloroplasty prevented gastric ulcer very effectively in young pig orthotopic liver transplantation.
Third Research : Results of the experiment to induced the immunoto-lerance are not clear yet. Survival of the experimental group which received donor's spleen cells was in days 28 and 84. In contrast, survival of the control group was in days 3, 5 and 34. Less