ELSEVIER 2Ghlorodeoxyadenosine in Combination With Cyclosporine Inhibits the Development of Transplant Arteriosclerosis in Rat Cardiac Allografts D.V. Cramer, G.D. Wu, F.A. Chapman, C. Marboe, and DR. Salomon ONG-TERM SURVIVAL following organ transplantation has been associated with a high frequency of vascular disease (transplant arteriosclerosis, TA) in the muscular arteries of the donor graft. It is estimated that approximately 50% of heart graft recipients have evidence of coronary vascular disease 5 years following transplantation.â The prevention of TA may depend on the development of more effective immunosuppression to prevent or treat chronic rejection without increasing the risk of adverse side effects. We have recently used a rat cardiac allograft model to evaluate an antitumor agent, 2-chlorodeoxyadenosine (2-CdA) in the prevention of TA. METHODS ducer cells, were reduced by 60% at 14 and 70% at 90 days Ptx in the treatment groups, indicating that 2-CdA has a prolonged, depletive effect on certain lymphocyte populations. DISCUSSION Heterotopic heart transplants were performed using LEW rats (RTlâ as the donor strain and F344 rats (RTlâ) as the recipients. ) Heart grafts were harvested at the end of a 90-day period posttransplantation (PTx). Heart samples were subjected to histological examination and vascular lesions were analyzed with a computerized digital image system. RESULTS Our preliminary results demonstrate that 2-CdA in combination with CsA inhibits the development of transplant arteriosclerosis in rat cardiac allografts. 2-CdA is a recently developed anticancer compound that also has immunosuppressive properties when used for the treatment of multiple sclerosis.2a3 Its effect on the immune system includes lymphocyte depletion of both T- and B-cell populations. 2-CdA inhibits the proliferative changes associated with the development of TA and suggests that this effect is primarily due to the drugâ unique mechanism of immunosuppression. s REFERENCES Our results indicate that a reduction in the incidence and severity of the vascular intimal proliferative (VIP) lesions was associated with the treatment using 2-CdA in combination with CsA when compared with controls receiving no treatment or treatment with CsA alone (Table 1). A reduction in the intimal thickening was 69.8% (P = .005) when compared with no treatment and 48.2% (P = .05) compared with the CsA monotherapy group. Examination of peripheral blood samples suggested that T-cell counts, especially CD4+ T-helperiinTable 1. Histological 1. Cramer, DV: In Medical intelligence Unit, R.G. Landes Company: Graft Arteriosclerosis in Heart Transplantation. Austin/ Georgetown, 1993 2. Beutler E: Lancet 340:952, 1992 3. Oberhuber G, Schmid T, Thaler W, et al: Transplantation 581743, 1994 From the Transplantation Biology Research Laboratory, National Institute of Transplantation, St Vincent Medical Center (D.V.C., G-D.W., F.A.C.), Los Angeles, California, Department of Pathology, University of Southern California School of Medicine (C.M.), Los Angeles, California, and the Department of Molecular and Experimental Medicine, The Scripps Research Institute (D.R.S.), La Jolla, California, USA. of LEW Cardiac Allografts Findings for 2-CdA Treated FM4 Recipients HistologicalScoreâ(Mean ? SD) VIP Group 1 N L3 S L PVF S MI MF 1.18 ? 0.37 0.55 k 0.27 0.83 ? 0.32 2.69 1.74 t 0.38 0.44 2 0.24 0.66 i- 0.39 0.39 + 0.36 NA 0.88 k 0.71 0.47 +- 0.27 0.61 ? 0.27 2.00 1.25 ? 0.71 0.28 2 0.16 0.16 k 0.1 0.28 ? 0.2 NA 1.17 5 0.29 1.40 + 0.22 1 .oo + 0.5 2.00 1.30 * 0.41 0.42 c 0.14 0.70 _f 0.22 0.83 + 0.29 2.16 1.35 -t 0.68 â VIP: Vascular intimal proliferation;PVF: perivascularfibrosis; Ml: myocardiuminflammation;MF: myocardiumfibrosis. â Group 1: P-CdA 0.1 mg/kg. CsA 2.5 mg/kg; Group 2: P-CdA 0.1 mg/kg, CsA 5 mg/kg; Group 3: P-CdA 1 mgikg, CsA 5 mg/kg; Group 4: historic control (nontreatment). *L: Large vessels; S: Small intramyocardial vessels. 0041-1315/97/$17.00 PII SO041 -1345(96)00326 0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 29, 616 (1997)
Transplantation Proceedings – Elsevier
Published: Feb 1, 1997
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera