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F12-8 The interaction between hepatic sinusoidal cells causing graft dysfunction in liver transplantation
Clinical and Research Forum/International Hepatology Communications 3 Suppl. (1995) $5-$36
F12-5
CONFUCIANISMANDORGANDONATION IN KOREA SooTae Kin~M.D.,Ph.D.,FACS
Professor Emeritus of Surgery Seoul National University, Hallym University, Korea Most Koreans are basically occupied with Confucianism as a religion, even now. We have one thousand history of Confucianism which has taught us that the body including hair and skin tom, from parents. Therefore one should not be injured by any means. This is the first obligation of its filial duty. We had a special punishment during the Yi dynasty( the last dynasty in Korea ). The worst punishment of a crime during one's life time, which was recognized after his d~th, was cutting the neck of his corpse out of his coffin. On March 16, 1988, the first liver transplantation was performed. The proOd success suppressed the blame of surgeons. But the nocessity of brain death as legal death steadly has been opened to the public. In June 1992, favorable response rate of transplantation from brain death patient was 81.2 %. In March 1992, after the 2nd liver transplantation, the prosecutor officially announced not to be prosecuted. The ministry of Heath and Welfare is now going to present the legislation for legal approval of brain death to the National Assembly. Current cases of cadavaric transplantation are as follnws, by 1993, 120 of kidney, by 1994, 42 of liver, 12 of pancreas, 28 of heart [n conclusion, even though cadavefie transplantation is going on without legal permission and some progress has been made. we have still many economical, socia], and religious problems.
F12-7
HEPATOCYTE TRANSPLANTATIONIN MULTILOCATIONS OF CONGENITALLY ENZYME DEFICIENT RATS F. Naknzawa,~ K. Onodera,~ K. Kato, 1 M. Sawa,' S. Kasai,~ M. Mitt, ~ T.Matsushita, 2 K.Funatsn 2 2nd Dept. of Surgery, Asahikawa Medical College, Asahikawa, Japan 2 Dept. of Chemical Engineering, Faculty of Engineering, Kyushu University, Fukuoka, Japan
The aim of this study was to investigate the efficacy of multilocational hepatocyte transplantation (HTx) including newly developed polyurethane form (PUF) in congenitally enzyme deficient rats. Methods: Ascorbic acid (AsA) biosynthetic enzyme deficient (ODS-Od/Od) rats were pretreated with 0.05%AAF for 4 days prior to 70% hepatectomy and HTx. (1) Hepatocytes isolated from the liver of congeneic rats were transplanted into the portal vein (Pv), spleen (Sp), omentum (Ore), mesentery (Ms), and peritoneum (Per). The recipients were divided into 6 groups as follows; I:Pv (n=10), II:Pv+Sp (n=10), III:Pv+Sp+Om (n=3), W:Pv+Sp+Om+Ms (n=7), V:Om+Ms+Per (n=5), VI:HTx(-) (n=10) (2) Hepatocytes were immobilized to collagen coated PUF (15x15x lmm). ODS-od/od rats (n=5) received 8-10 PUFs in Ore, Ms, and Per. Results: (1)Survival rates at 8 M after HTx were 75, 80, 67, 71, 0 and 0% for groups I, II. III, IV, V, and VI, respectively. AverageAsA value of the survived rats in groups I-W was 1.16/~ g/ml, and rats in group IV showed the highest value (1.87p g/ml). Histological examination showed small foci of hepatocytes in fatty tissues of Om and Ms, and intrasplenicany transplanted hepatocytes recomposed hepatic cord structure. (2) Capillaries and connective tissues were observed around PUFs at 2 M after HTx, and small foci of surviving hepatocytes w~e found among connective tissues. However, transplantation of hepateeytes attached to PUFs could not improve the survival rates. Conclusion: Transplanted hepat~cytes in multilocations survived for long periods of time and improved survival rate of ODS-Od/od rats.
$35
F12-6
OPEN THE DOOR FOR ORGAN DONATION IN THE FAR EAST WITH HONG KONG UNIVERSITYEXPERIENCE.
S.T. Fan, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong From October 1991 to April 1995, 20 urthotopic liver transplantations were performed in the Department of Surgery, The University of Hong Kong, Queen Mary Hospital. There wer~ fifteen adults and six paediatric recipients with a mean age of 29.9 years (range 8 months to 62 years). The underlying liver diseases were biliary atresia (n=6), alcoholic cirrhosis (n =4), fulminant hepatic failure (n =2), polycystic liver (n =2), primary biliary cirrhosis (n=2), secondary biliary cirrhosis (n=l), cryptogenic cirrhosis (n=2) and hepatitis B related cirrhosis (n= 1). Four patients were in critical condition in ICU before transplantation (UNOS status 4). Fifteen cadaveric, four living related and one living unrelated (interspouse) grafts were used. The weight of living donor grafts ranged from 220 gm to 623 gm. One patient received combined liver and kidney transplant. There was no intraoperative or 30-day mortality. Two patients died from graR failure due to primary non-function and resistent rejection respectively because no graft was available fnr retransplantation. The overall I-year graft and patient survival rates were 87.5 %. Survival rates for cadaveric and living donor grafts were 87% and 100% respectively. Early results of liver transplantation in Horlg Kong is encouraging. Shortage (ff suitable cadaveric organ is a major issue and will limit the possibility of improving patient survival by retransplantation. The use of living donor graft is a viable option in selected patients.
F12-8 THE INTERACTION BETWEEN HEPATIC SINUSOIDAL CELLS CAUSING GRAFT DYSFUNCTION IN LIVERTRANSPLANTATION H.Sakurai, M.K.itagawa, T.Noguchi, Y.Kawarada FirstDept. of Surgery, Mie Univ.Schoolof Medicine,Tsu,Japan [Purpose] To investigate the functional dynamics of hepatic sinusoidal cells and the pathophysiology of the microcirculatory impairment in the grafted liver. [Methods] Orthotopic total liver transplantation was performed in adult mongrel dogs. The grafted livers were divided into two groups according to ischemic time, during which they were perfused with cold lactated Ringer's solution. Group I (n=10): ischemic time of 60 min., Group II (n=10): ischemic time of 120 min. Examined in vivo were hepatic tissue blood flow (HBF), arterial ketone body ratio (AKBR), while endothelin-1 (ET-1) and TGF- 13 mRNA levels were examined in cell culture. [Results] HBF in Group I recovered to 90% of the preoperative value by POD5 showing transient decrease from 6 to 24 hours after hepatic blood reflow. AKJ3R was lowest prior to reflow, and increased to preoperative level 6 hours after reflow in Group I. While those of Group II remained significantly lower than Group I. In the supernatant of non-parenchymal cell (NPC) culture, ET-1 levels were significantly higher in Group II than in Group I.ln both groups ET-1 in sinusoidal endothelial cell culture was significantly lower than '~hose in NPC. TGF-/3 mRNA in Kupffer cell was significantly higher in Group II than in Group I. [Conclusion] Recovery from microcirculation disorder of liver graft was delayed due to prolonged duration of cold perfusion and the upregulated production of liver derived ET-1, increasing the susceptibility to liver failure. In sinusoidal cell culture study, ET-1 production was enhanced via the cytokine network (TGF/3 ) in the presence of Kupffer ceils.
F12-5
CONFUCIANISMANDORGANDONATION IN KOREA SooTae Kin~M.D.,Ph.D.,FACS
Professor Emeritus of Surgery Seoul National University, Hallym University, Korea Most Koreans are basically occupied with Confucianism as a religion, even now. We have one thousand history of Confucianism which has taught us that the body including hair and skin tom, from parents. Therefore one should not be injured by any means. This is the first obligation of its filial duty. We had a special punishment during the Yi dynasty( the last dynasty in Korea ). The worst punishment of a crime during one's life time, which was recognized after his d~th, was cutting the neck of his corpse out of his coffin. On March 16, 1988, the first liver transplantation was performed. The proOd success suppressed the blame of surgeons. But the nocessity of brain death as legal death steadly has been opened to the public. In June 1992, favorable response rate of transplantation from brain death patient was 81.2 %. In March 1992, after the 2nd liver transplantation, the prosecutor officially announced not to be prosecuted. The ministry of Heath and Welfare is now going to present the legislation for legal approval of brain death to the National Assembly. Current cases of cadavaric transplantation are as follnws, by 1993, 120 of kidney, by 1994, 42 of liver, 12 of pancreas, 28 of heart [n conclusion, even though cadavefie transplantation is going on without legal permission and some progress has been made. we have still many economical, socia], and religious problems.
F12-7
HEPATOCYTE TRANSPLANTATIONIN MULTILOCATIONS OF CONGENITALLY ENZYME DEFICIENT RATS F. Naknzawa,~ K. Onodera,~ K. Kato, 1 M. Sawa,' S. Kasai,~ M. Mitt, ~ T.Matsushita, 2 K.Funatsn 2 2nd Dept. of Surgery, Asahikawa Medical College, Asahikawa, Japan 2 Dept. of Chemical Engineering, Faculty of Engineering, Kyushu University, Fukuoka, Japan
The aim of this study was to investigate the efficacy of multilocational hepatocyte transplantation (HTx) including newly developed polyurethane form (PUF) in congenitally enzyme deficient rats. Methods: Ascorbic acid (AsA) biosynthetic enzyme deficient (ODS-Od/Od) rats were pretreated with 0.05%AAF for 4 days prior to 70% hepatectomy and HTx. (1) Hepatocytes isolated from the liver of congeneic rats were transplanted into the portal vein (Pv), spleen (Sp), omentum (Ore), mesentery (Ms), and peritoneum (Per). The recipients were divided into 6 groups as follows; I:Pv (n=10), II:Pv+Sp (n=10), III:Pv+Sp+Om (n=3), W:Pv+Sp+Om+Ms (n=7), V:Om+Ms+Per (n=5), VI:HTx(-) (n=10) (2) Hepatocytes were immobilized to collagen coated PUF (15x15x lmm). ODS-od/od rats (n=5) received 8-10 PUFs in Ore, Ms, and Per. Results: (1)Survival rates at 8 M after HTx were 75, 80, 67, 71, 0 and 0% for groups I, II. III, IV, V, and VI, respectively. AverageAsA value of the survived rats in groups I-W was 1.16/~ g/ml, and rats in group IV showed the highest value (1.87p g/ml). Histological examination showed small foci of hepatocytes in fatty tissues of Om and Ms, and intrasplenicany transplanted hepatocytes recomposed hepatic cord structure. (2) Capillaries and connective tissues were observed around PUFs at 2 M after HTx, and small foci of surviving hepatocytes w~e found among connective tissues. However, transplantation of hepateeytes attached to PUFs could not improve the survival rates. Conclusion: Transplanted hepat~cytes in multilocations survived for long periods of time and improved survival rate of ODS-Od/od rats.
$35
F12-6
OPEN THE DOOR FOR ORGAN DONATION IN THE FAR EAST WITH HONG KONG UNIVERSITYEXPERIENCE.
S.T. Fan, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong From October 1991 to April 1995, 20 urthotopic liver transplantations were performed in the Department of Surgery, The University of Hong Kong, Queen Mary Hospital. There wer~ fifteen adults and six paediatric recipients with a mean age of 29.9 years (range 8 months to 62 years). The underlying liver diseases were biliary atresia (n=6), alcoholic cirrhosis (n =4), fulminant hepatic failure (n =2), polycystic liver (n =2), primary biliary cirrhosis (n=2), secondary biliary cirrhosis (n=l), cryptogenic cirrhosis (n=2) and hepatitis B related cirrhosis (n= 1). Four patients were in critical condition in ICU before transplantation (UNOS status 4). Fifteen cadaveric, four living related and one living unrelated (interspouse) grafts were used. The weight of living donor grafts ranged from 220 gm to 623 gm. One patient received combined liver and kidney transplant. There was no intraoperative or 30-day mortality. Two patients died from graR failure due to primary non-function and resistent rejection respectively because no graft was available fnr retransplantation. The overall I-year graft and patient survival rates were 87.5 %. Survival rates for cadaveric and living donor grafts were 87% and 100% respectively. Early results of liver transplantation in Horlg Kong is encouraging. Shortage (ff suitable cadaveric organ is a major issue and will limit the possibility of improving patient survival by retransplantation. The use of living donor graft is a viable option in selected patients.
F12-8 THE INTERACTION BETWEEN HEPATIC SINUSOIDAL CELLS CAUSING GRAFT DYSFUNCTION IN LIVERTRANSPLANTATION H.Sakurai, M.K.itagawa, T.Noguchi, Y.Kawarada FirstDept. of Surgery, Mie Univ.Schoolof Medicine,Tsu,Japan [Purpose] To investigate the functional dynamics of hepatic sinusoidal cells and the pathophysiology of the microcirculatory impairment in the grafted liver. [Methods] Orthotopic total liver transplantation was performed in adult mongrel dogs. The grafted livers were divided into two groups according to ischemic time, during which they were perfused with cold lactated Ringer's solution. Group I (n=10): ischemic time of 60 min., Group II (n=10): ischemic time of 120 min. Examined in vivo were hepatic tissue blood flow (HBF), arterial ketone body ratio (AKBR), while endothelin-1 (ET-1) and TGF- 13 mRNA levels were examined in cell culture. [Results] HBF in Group I recovered to 90% of the preoperative value by POD5 showing transient decrease from 6 to 24 hours after hepatic blood reflow. AKJ3R was lowest prior to reflow, and increased to preoperative level 6 hours after reflow in Group I. While those of Group II remained significantly lower than Group I. In the supernatant of non-parenchymal cell (NPC) culture, ET-1 levels were significantly higher in Group II than in Group I.ln both groups ET-1 in sinusoidal endothelial cell culture was significantly lower than '~hose in NPC. TGF-/3 mRNA in Kupffer cell was significantly higher in Group II than in Group I. [Conclusion] Recovery from microcirculation disorder of liver graft was delayed due to prolonged duration of cold perfusion and the upregulated production of liver derived ET-1, increasing the susceptibility to liver failure. In sinusoidal cell culture study, ET-1 production was enhanced via the cytokine network (TGF/3 ) in the presence of Kupffer ceils.