CYTOMEGALOVIRUS INFECTION-ENHANCED CARDIAC ALLOGRAFT VASCULOPATHY IS ABOLISHED BY DHPG PROPHYLAXIS IN THE RAT

Background A wealth of clinical and experimental evidence exists for c ytomegalovirus (CMV) infection as an accelerating factor in the develo pment of cardiac allograft vasculopathy. In this study, the impact of 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG) on rat CMV infection- enhanced cardiac allograft vasculopathy is investigated. Methods and R esults Heterotopic rat cardiac allografts were performed from the DA t o the WF rat strain, and the recipients were immunosuppressed with cyc losporine A 2 mg.kg(-1).d(-1) SC for a period of 90 days until the end of experiment. Two groups of recipients were infected intraperitoneal ly with 10(5) plaque-forming units of rat CMV, whereas one group was l eft noninfected and used as controls. One group of rat CMV-infected ra ts was treated with DHPG with an initial dose of 20 mg/kg IP and a mai ntenance dose of 10 mg/kg IP twice a day from 1 day before transplanta tion to 30 days after transplantation. Compared with noninfected rats, rat CMV infection was associated with a significant increase in intim al thickening, from 0.68 +/- 0.10 to 1.30 +/- 0.12 score units (P < .0 1), and double the number of vessels affected (P < .01). DHPG treatmen t significantly reduced intimal thickening in rat CMV-infected rats, f rom 1.30 +/- 0.12 to 0.68 +/- 0.13 score units (P < .01), and halved t he number of vessels affected (P < .01). Conclusions The present resul ts demonstrate that DHPG prophylaxis entirely abolishes the accelerati ng effect of rat CMV infection on cardiac allograft vasculopathy in im munosuppressed rat recipients, which is consistent with our earlier fi ndings demonstrating a similar effect in nonimmunosuppressed rat aorti c allografts. Taken together, these results suggest that DHPG might be useful in the prevention of CMV-accelerated cardiac allograft vasculo pathy among heart transplant recipients.