Document Detail

Rapamycin inhibits transplant vasculopathy in long-surviving rat heart allografts.
MedLine Citation:
PMID:  7570985     Owner:  NLM     Status:  MEDLINE    
We have examined the effects of rapamycin (RPM) on transplant vasculopathy in long-surviving F344 rat heart allografts transplanted heterotopically into Lewis recipients. RPM was administered intraperitoneally for the first 14 days in groups 1 and 2 (0.5 and 2 mg/kg/day), and daily throughout the follow-up period in groups 3 (0.5 mg/kg/day) and 4 (5 mg/kg for 14 days, followed by a maintenance dose of 2.5 mg/kg/day). Treatment with low dose cyclosporine (CsA; 1.5 mg/kg/day) in combination with RPM (0.5 mg/kg/day for 14 days) (group 5) and immunosuppression with CsA only (5 mg/kg for 14 days, followed by 1.5 mg/kg/day) (group 6) were also examined. F344 isograft recipients treated with RPM (0.5 mg/kg/day for 14 days) (group 7), those that were untreated (group 8), and hearts in naive F344 animals (group 9) served as controls. Grafts of group 1 were removed at 50, 75, 100, 150, and 200 days and infiltrating cell populations and surface molecules were compared with those of the other groups at 100 days. All allografts in treated hosts functioned > 100 days; in contrast, grafts in untreated recipients were rejected acutely by 8 +/- 1 days (MST +/- SD). The incidence of transplant vasculopathy in group 1 increased progressively (MST +/- SD = 10 +/- 2%, 59 +/- 7%, 85 +/- 15%, and 80 +/- 12% at 50, 100, 150, and 200 days, respectively), as manifested by myointimal proliferation with dense mononuclear infiltration (predominantly ED1+ macrophages). Numbers of MHC class II+ infiltrating cells were prominent, as was expression of adhesion molecules and cytokines. The incidence of graft disease and extent of cellular infiltration at 100 days was significantly lower in animals receiving increased maintenance doses of RPM (for groups 2, 3, and 4: 25 +/- 15%, 22 +/- 11%, and 10 +/- 3%, respectively; P < 0.005). CsA treatment either in combination with RPM or alone (groups 5 and 6) failed to improve transplant vasculopathy, but reduced mononuclear cell infiltration. Isografts (groups 7 and 8) and naive hearts (group 9) developed no structural abnormalities throughout the follow-up period, regardless of RPM treatment. We conclude that the extent of transplant vasculopathy can be reduced markedly in this rat cardiac transplant model with maintenance RPM. Addition of CsA modifies the morphological picture but does not improve myointimal proliferation.
C Schmid; U Heemann; H Azuma; N L Tilney
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Transplantation     Volume:  60     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  1995 Oct 
Date Detail:
Created Date:  1995-11-22     Completed Date:  1995-11-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  729-33     Citation Subset:  IM    
Surgical Research Laboratory, Harvard Medical School, Boston, Massachusetts, USA.
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MeSH Terms
Cell Division / drug effects
Cyclosporine / therapeutic use
Dose-Response Relationship, Drug
Heart Transplantation / adverse effects*
Immunosuppressive Agents / therapeutic use*
Polyenes / therapeutic use*
Rats, Inbred F344
Rats, Inbred Lew
Time Factors
Tunica Intima / cytology,  drug effects
Vascular Diseases / etiology,  pathology,  prevention & control*
Ventricular Function / drug effects
Grant Support
9R 01 DK 46190-20/DK/NIDDK NIH HHS
Reg. No./Substance:
0/Immunosuppressive Agents; 0/Polyenes; 53123-88-9/Sirolimus; 59865-13-3/Cyclosporine

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