Viral serine proteinase inhibitor (SERP-1) effectively decreases the incidence of graft vasculopathy in heterotopic heart allografts

Background. Graft vascular disease (GVD) is the most common cause of late g raft failure in solid organ transplantation. Recent studies have shown good efficacy of a novel nontoxic viral-derived serine proteinase inhibitor (SE RP-1) in preventing postangioplasty restenosis. The current study was desig ned to test whether short-term treatment with SERP-1 was effective in reduc ing the incidence of GVD in a solid organ transplant. Methods. Piebald-Virol-Glaxo (PVG) donor hearts were transplanted into Augu st-Copenhagen-Irish (ACI) recipients and observed for 90 days. All recipien ts (n=60) were treated with microemulsion cyclosporine (CsA) 7.5 mg/kg per gavage from day 0 to day 9 and randomized into 4 groups. SERP-1 was given i ntravenously. Group I received CsA monotherapy; group II, C&A+SERP-1 1 ng(g (postoperative days 0-9); group III, C&A+SERP-1 10 ng/g (postoperative day s 0-9); and group IV, C&A+SERP-1 10 ng/g (postoperative days 0-9, 30, and 6 0). Graft viability was monitored by palpation, and GVD was assessed by mor phometry. Results. Two animals in group I rejected their allografts on postoperative days 7 and 14, 1 animal in group II rejected the allograft (postoperative d ay 31), and none in group III and IV rejected the allografts. At 90 days po stoperative, 23.8% of all coronary vessels showed evidence of GVD in group 1, 18.4% in group II, 12.9% in group III, and 11.8% in group IV. The differ ence in incidence of GVD was significant between groups I and III (P<0.05) and groups I and IV (P<0.05). Treatment with SERP-1 was well tolerated, and all animals regained weight quickly postsurgery. Conclusions. Treatment of allograft recipients with SERP-1 in combination w ith CsA early after transplantation significantly decreases the incidence o f GVD when compared to grafts treated with only CsA. These results demonstr ate the clinical potential for this novel serine protease inhibitor to prev ent GVD in solid organ transplantation.