[Effect of Yunnan-cobra venom factor in overcoming acute humoral rejection after allograft cardiac transplantation in presensitized recipients: experiment with rats].
OBJECTIVE
To investigate the effect of Yunnan-cobra venom factor (Y-CVF) in overcoming acute humoral rejection after allograft cardiac transplantation in presensitized recipients.


METHODS
Fifteen Lewis rats received the transplantation of full-thickness skin graft of BN rats three times so as to be presensitized. Fifteen pairs of Lewis rat, as recipients of heart, and BN rat, as heart donors, were randomly divided into 2 groups: experimental group (n = 8), and control group (n = 7). The Lewis rats in the experimental group received heart transplantation of the heart of the BN rat 7 approximately 10 days after the third skin transplantation, and were injected with Y-CVF 80 microg/kg 24 hours before the heart transplantation. The Lewis rat in the control group received only the heart transplantation without Y-CVF injection. Blood samples were collected from all rats before pre-sensitization and 7 days after the third skin transplantation so as to determine the titer of anti-BN rat lymphocyte antibody. 0 and 24 hours, and 6 and 8 days after Y-CVF injection blood samples were collected from the Lewis rats to determine the total complement activity with the complement activity before Y-CVF injection defined as 100%. The survival time of the transplanted heart was observed. After the transplanted hearts stopped to beat, they were resected and underwent HE staining and microscopy. Immunohistochemistry was used to examine the deposition of IgG and complement 3 (C3).


RESULTS
The titer of anti-BN rat lymphocyte antibody was 0 before the pre-sensitization, and increased to 1:1028 - 1:2056 7 days after the third skin pre-sensitization. The serum total complement activity of the Lewis rats decreased to 0 twenty-four hours after the Y-CVF injection, recovered to 2.01% - 15.41% 6 days after, and returned to the normal level (89.61% - 109.46%) 8 days after. The mean survival time of the transplanted hearts of the control group was 12.71 +/- 13.94 hours (with a range of 1.5 - 15 hours), significantly shorter than that of the experimental group (99.50 +/- 38.72 hours, with a range of 23 - 153 hours, P < 0.01). Pathological examination showed that the acute humoral rejection in the control group was mainly complement-dependent antibody-mediated humoral rejection characterized by intravascular thrombosis, and that in the experimental group was mainly cellular rejection, characterized by extensive infiltration of mononuclear cells. Immunohistochemistry showed that remarkable IgG deposition was seen in the cardiac muscle cells and vascular endothelial cells in both groups; however, C3 deposition in vascular endothelial cells could be seen only in the control group.


CONCLUSIONS
Administration of CVF is effective in overcoming the acute humoral rejection after allograft cardiac transplantation in presensitized recipients.
Li
Rong
R
Institute of Organ Transplantation, Key Laboratory of Organ Transplantation (HUST), Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
Chen
Gang
G
Guo
Hui
H
Wang
Da-wei
DW
Xie
Lin
L
Wang
Shu-sen
SS
Wang
Wan-yu
WY
Xiong
Yu-liang
YL
Chen
Shi
S
D000818:Animals; D004546:Elapid Venoms / Q000627:therapeutic use*; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000379:methods*; D007074:Immunoglobulin G / Q000276:immunology; D011897:Random Allocation; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016038:Skin Transplantation / Q000379:methods; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
D004546:Elapid Venoms; D007074:Immunoglobulin G; C016310:cobra venom factor