AEB-071 Versus Tacrolimus Monotherapy to Prevent Acute Cardiac Allograft Rejection in the Rat: A Preliminary Report

We investigated the Brown Norway-Lewis rat strain combination for cardiac graft survival over 30 days after transplantation using varying doses of oral AEB and Tac monotherapy. Grafts were monitored by daily palpation; cessation of palpable ventricular contraction was considered to be rejection. Apart from necropsy, we performed histologic examinations of cardiac graft at 7 days after transplantation. In untreated recipients, allograft mean survival times (MST) was 6.83 ± 0.41 days. AEB at 15, 30, or 60 mg/kg versus Tac at 1.2 mg/kg significantly prolonged graft survival to a MST of 12.33 ± 1.21, 16.67 ± 1.21, and 19.33 ± 3.83, versus 17.00 ± 6.90 days, respectively. Histologic assessment at 7 days after transplantation showed that high-dose AEB significantly decreased the histologic rejection score, indicative of decreased inflammatory cell infiltration into the graft. These results suggested that the administration of AEB (medium or high-dose), a PKC inhibitor, mitigated acute rejection and displayed significantly longer MST, similar to high-dose Tac after heterotopic heart transplantation in the rat.