Effects Of Complement Depletion With CVF On Acute Rejection After Cardiac Allotransplantation In Inbred Strain Rat

Objective and Background: Cardiac allotransplantation is now recongnized effective treatment for end-stage heart disease with 1-year survival rates of up 90%.However,acute cardiac allograft rejection occurrs in approximately 50-60% of recipients and result in compromised allograft function or even sudden death of the patient. Traditional immunology recognizes that the adaptive immune response induced by T cells is the main mechanism for the allograft rejection.But we know regulatory cell-mediated tolerance does not protect against chronic rejection and kidney transplantation into complement-inhibited rats reduces subsequent inflammation of the graft.Complement activation has recently been implicated as a contributing factor to early and late allograft dysfunction in cardiac transplantation.but the role is unclearly.The optimal solve style against organ transplantation rejection is the specific immunologic tolerance. And further investigation has crucial value not only for extending the mechanism of allograft rejection, but also for exploring new method and medicament to inhibit the allograft rejecton.Methods: To achieve our goals, we conducted the following works:1. we used the technique which was described by Ono to establish an abdominal heterotopic cardiac allotransplantation model in inbred strain rat.2. After injection with low dose CVF in the Lewis rat, we used the CH₅₀ test to measure the variation of C3 activity in serum.3. After injecting CVF in this cardiac allotransplantation model, We observe thesurvival and histology of the allograft.Results:1. We had succeeded to establish the model of heart heterotopic transplantation in inbred strain rat.2. CVF activity was inhibited to about 10% of pretreatment (normal) activity at days 1 to 2 after injection CVF. At day 8, hemolytic activity was still depressed to a mean of 68.81%.3. The survival time of cardiac allograft treated with CVF was significantly prolonged. In control animals, with uninhibited Complement activity, C3 was deposited in the cardiac vascular from days 1 to 6, and their endothelial characterized swelling, lifting, and stripping. The grafts of CVF-treated animals, in contrast, showed no C3 staining, and their endothelial had not obvious change. Compare with the control animals, the extent of infiltration by T cells of CD3⁺ phenotype were significantly reduced in CVF-treated animals.Conclusions: We used CVF to deplete the complement in the serum of the inbred rat cardiac allograft model, and observed the survival and histology of the allograft. We had main conclusions are as follows:1. The modified Ono technique is a stable method to establish the animal model of heterotopic cardiac allotransplantation.2. The CVF which provided by the Kunming Institute of Zoology has a highly anticomplementary activity even in a low dose.3. CVF can inhibit acute rejection and significantly prolong the survival time of cardiac allograft.