Cytomegalovirus (CMV) infection accelerates transplant vascular sclerosis (TVS) and chronic rejection(CR) in both human and animal solid organ transplantation models. The host/viral mechanisms involved in this process are unclear. We examine the role of the rat CMV (RCMV)-encoded chemokine-receptor R33 in the development of TVS using a rat heart transplantation/CR model. F344 heart grafts were transplanted heterotopically into Lewis recipients. The ability of RCMV lacking the R33 gene (RCMV-∆r33) to accelerate CR/TVS (neointimal index, NI) was compared to wild-type (WT) RCMV. Allograft recipients were infected with 1 × 10 5 pfu RCMV or RCMV-∆r33 on postoperative day (POD) 1.Grafts from RCMV-∆r33-infected recipients demonstrated an accelerated time to allograft CR compared to grafts from uninfected recipients (POD = 56 vs. 90), this was slower than that seen in grafts from WT-RCMV-infected recipients (POD = 45). Similarly, the degree of graft TVS formation at terminal rejection in RMCV-∆r33 infected recipients was more severe than uninfected recipients (NI = 63 vs. 45), yet not as severe as in WT-RCMV infected recipients (NI = 83). In parallel, RCMV-∆r33 failed to induce vascular smooth muscle

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Since 2002 our transplant program has utilized a steroid free, cyclosporine (CSA)- and rapamycin (RAPA)-based maintenance immunosuppression regimen. In cases where it has been desirable to avoid the potential nephrotoxicity with this regimen we have used mycophenolic acid (MPA) as our "switch" drug of choice. Both mycophenolate mofetil (MMF) (Roche Inc., Nutley, NJ, USA) and enteric-coated MPA (ECM) (Novartis, East Hanover, NJ, USA) have been used. In this study, we retrospectively compared the tolerability of the two formulations of MPA. Thus we compared 103 recipients switched to RAPA/MMF (RMM group) to 114 switched to RAPA/ECM (REC group). There was a significantly higher incidence of patients requiring dose changes and drug discontinuation in the RMM group, as well as an increased frequency of dose changes. There were significantly more acute rejection episodes and kidney losses in the dose adjustment vs. no dose adjustment patients. However, when comparing the incidence of acute rejection and kidney loss between the RMM and REC groups, there was no significant difference. We conclude that in this cohort of recipients, the ECM formulation of MPA was better tolerated than the MMF formulation, resulting in fewer patients requiring dose adjustments or drug discontinuation.