PREOPERATIVE DEPLETION OF C3 IMPROVES THE SURVIVAL OF GUINEA PIG-TO-RAT CARDIAC XENOGRAFT RECIPIENTS

Rat strains with congenitally reduced total hemolytic complement activ ity do not reject cardiac xenografts hyperacutely. Prolongation of gra ft survival in the guinea pig-to-C6-deficient PVG rat donor/recipient combination has been observed. However, experience with this model has been complicated by a high postoperative mortality from respiratory d istress. The authors hypothesized that placement of the xenograft resu lted in local activation of complement, which contributed to remote pu lmonary injury leading to respiratory dysfunction. To test this hypoth esis, an attempt was made to reduce early complement component activat ion with the use of an antibody to rat C3 in C6-deficient PVG recipien ts. Six of eight untreated C6-deficient PVG recipients died in the imm ediate postoperative period with vigorously beating heart grafts, wher eas only 2 of 14 C6-deficient recipients pretreated with anti-rat C3 a ntibody died within 24 h postoperatively. Although pretreatment with a nti-C3 antibody improved survival of recipients, the duration of cardi ac xenograft survival was similar whether the recipients were pretreat ed or not. The use of anti-C3 antibody in CG-deficient rats is a valid approach to studying xenotransplantation in the absence of hyperacute rejection and has an additional advantage in that it does not require the use of expensive reagents such as cobra venom factor.