Experimental Research of Xeno Heart Transplantation

1990 Fiscal Year Final Research Report Summary

• Project/Area Number: 62480301
• Research Category: Grant-in-Aid for General Scientific Research (B)
• Allocation Type: Single-year Grants
• Research Field: Thoracic surgery
• Research Institution: National Cardiovascular Center, Research Institute
• Principal Investigator: SADA Masaharu National Cardiovascular Center, Research Institute, Dept. of Surgical Research, 実験治療開発部, 研究員 (20162399)
• Co-Investigator(Kenkyū-buntansha): YUTANI Chikao National Cardiovascular Center, Dept. of Clinical Laboratory, 臨床検査部, 医長 ; KAWAZOE Kouhei National Cardiovascular Center, Dept. of Cardiovascular Surgery, 第二病棟部, 医長 ; SAKAKIBARA Izumi Toray Institute, Dept of Pharmacology, 薬理研究室, 研究員 (90153866) ; SASAKI Hidemiki Kanazawa Medical College Dept. of Cardiovascular Surgery, 胸部外科, 講師 (60153996)
• Project Period (FY): 1987 – 1989
• Keywords: Xeno transplantation / Hyperacute resection / Histocomphtibility antigens / Mixed lymphocyte reaction / Xeno antibody

Research Abstract

1. Histopathological Changes on Macaque Hearts Perfused with Human Blood by Using Cardio-pulumonary Machine.
(1) Case 1 : Coronary Perfusion by Using ABO Imcompatible Human Whole Blood
(2) Case 2 : Coronary Perfusion by Using ABO Compatible Human Whole Blood
(3) Case 3 : Coronary Perfusion by Using ABO Compatible and Plasma Removed Human Blood
At the macroscopy, case 1 and 2 were observed edema and diffuse bleeding within 15 minutes after coronary perfusion started. After 30 minutes, Macaque hearts resulted in ventricular fibrillation and arrested. Case 3 was well beating and there was no macroscopic changes during observation. At the histopathological examination of RV, LV and IVS, case 1 and 2 were observed severe interstitial bleeding, contraction band necrosis, mononuclear infiltration and intra-arterial thrombus. But patchy necrosis was observed all cases. It was suggested that these histopathological changes like a hyperacute rejection were due to xeno-antibodies in human plasma.
2. A nalysis of cross-reactive Macaque histocompatibility antigens by using HLA alloantisera derived from human and monoclonal antibodies against HLA antigens.
Four hundred and sixty three HLA-class I and 81 monoclonal antibodies against HLA-class I antigens, submitted to 10th International Histocompatibility Workshop, were typed by Macaque lymphocytes using complement dependent cytotoxicity test. In 136 of 463 alloantisera were reacted strongly because of xeno-antibodies. HLA antigens, across the barrier of species, defined mono-specific were HLA-A1, -A2, -B40 (w60, w61), -B5 (51, w52), -B27, -21, -Cw1 and Cw2. HLA Antigens defined multispecific were A10 (25, 26) -Aw19 (31, 32, w33), B5-B35-B15 (w62, w63), a part of B7-B27, a part of B7-B40 (w60, w61) and B12 (44, 45) -B21-B5. It was suggested the possibility that histocompatibility antigens, across the barrier of species, were defined by using common HLA antisera and were able to select the suitable donor for xeno-transplantation from the obtained matching grades.