Increased rat cardiac allograft survival by the glycosaminoglycan pentosanpolysulfate

Background. Modulation of the inflammatory response has proven to be of ben efit in salvaging cardiac allografts at risk of irreversible injury. Pentos an polysulfate (PPS), like heparin, is a negatively charged sulfated glycos aminoglycan (GAG) that possesses antiinflammatory properties including the ability to inhibit activation of the complement system. This study was cond ucted to determine the potential of PPS to prolong allograft survival in an experimental model of cardiac transplantation. Materials and methods. A heterotopic cardiac transplant was performed by im planting the heart from fetal Brown Norway rats into the ear pinnae of adul t Lewis rats. Vehicle (saline) or PPS (30 mg/kg) was administered subcutane ously immediately after transplantation and daily thereafter (n = 6 in each group). Another GAG, heparin, was also analyzed to determine the effect of anticoagulation on transplant survival (n = 6). Results. Treatment with PPS significantly (P < 0.05) increased allograft su rvival time as compared to vehicle-treated animals (8.0 +/- 0.3 days vs 5.5 +/- 0.5 days). The results noted with PPS were similar to those observed i n cyclosporine (10 mg/kg; n = 6) treated animals (8.25 +/- 0.25 days). Trea tment with heparin (300 U/kg/day) did not significantly prolong cardiac gra ft survival time, suggesting that anticoagulation is not sufficient to prol ong transplant survival. Analysis of tissue histology showed diminished tra nsplant rejection as evidenced by decreased white blood cell infiltration a nd cellular necrosis. Conclusions. The results of this study indicate that PPS possesses the abil ity to prolong cardiac transplant viability in a heterotopic cardiac transp lant model, independent of its anticoagulant actions. (C) 1999 Academic Pre ss.