Ch. Suh et al., PREOPERATIVE DEPLETION OF C3 IMPROVES THE SURVIVAL OF GUINEA PIG-TO-RAT CARDIAC XENOGRAFT RECIPIENTS, Journal of investigative surgery, 10(1-2), 1997, pp. 37-40
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.