Document Detail

Cytomegalovirus infection-enhanced cardiac allograft vasculopathy is abolished by DHPG prophylaxis in the rat.
MedLine Citation:
PMID:  9193428     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: A wealth of clinical and experimental evidence exists for cytomegalovirus (CMV) infection as an accelerating factor in the development 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 RESULTS: Heterotopic rat cardiac allografts were performed from the DA to the WF rat strain, and the recipients were immunosuppressed with cyclosporine A 2 s.c. for a period of 90 days until the end of experiment. Two groups of recipients were infected intraperitoneally with 10(5) plaque-forming units of rat CMV, whereas one group was left noninfected and used as controls. One group of rat CMV-infected rats was treated with DHPG with an initial dose of 20 mg/kg i.p. and a maintenance dose of 10 mg/kg i.p. twice a day from 1 day before transplantation to 30 days after transplantation. Compared with noninfected rats, rat CMV infection was associated with a significant increase in intimal thickening, from 0.68 +/- 0.10 to 1.30 +/- 0.12 score units (P < .01), and double the number of vessels affected (P < .01). DHPG treatment significantly reduced intimal thickening in rat CMV-infected rats, from 1.30 +/- 0.12 to 0.68 +/- 0.13 score units (P < .01), and halved the number of vessels affected (P < .01). CONCLUSIONS: The present results demonstrate that DHPG prophylaxis entirely abolishes the accelerating effect of rat CMV infection on cardiac allograft vasculopathy in immunosuppressed rat recipients, which is consistent with our earlier findings demonstrating a similar effect in nonimmunosuppressed rat aortic allografts. Taken together, these results suggest that DHPG might be useful in the prevention of CMV-accelerated cardiac allograft vasculopathy among heart transplant recipients.
K Lemström; R Sihvola; C Bruggeman; P Häyry; P Koskinen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  95     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1997 Jun 
Date Detail:
Created Date:  1997-07-17     Completed Date:  1997-07-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2614-6     Citation Subset:  AIM; IM    
Transplantation Laboratory, University of Helsinki, Finland.
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MeSH Terms
Antiviral Agents / therapeutic use*
Coronary Disease / prevention & control*,  virology*
Cytomegalovirus Infections / complications*,  physiopathology
Ganciclovir / therapeutic use*
Heart / virology*
Heart Transplantation*
Rats, Inbred Strains
Rats, Inbred WF
Reg. No./Substance:
0/Antiviral Agents; 82410-32-0/Ganciclovir

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