Inhibition of Graft Coronary Arteriosclerosis After Heart Transplantation

Soukiasian, Harmik J.; Czer, Lawrence S. C.; Hai-Mei Wang; Luthringer, Daniel; Charles Wang; Kamlot, Andreas; Quartel, Adrian; Trento, Alfredo
October 2004
American Surgeon;Oct2004, Vol. 70 Issue 10, p833
Academic Journal
Graft coronary arteriosclerosis (GCA) is the leading cause of long-term mortality after heart transplantation (HTx). The goal of this study was to demonstrate that inhibition of immune-mediated injury by cyclosporine (CsA) protects the allograft from GCA. ACI-to-Lewis rat allografts were disparate in major and nonmajor histocompatibility loci. Isografts (Lewis-Lewis) were controls. Treatment groups received either olive oil or CsA at 2.5, 5, 10, or 20 mg/kg/day for 3 months. Histology (elastin) and immunohistochemistry using monoclonal antibodies to CD4, CD8, CD45R, RTIB, CDllb/c, CD25, and α-actin was performed to examine the epicardial and intramyocardial coronary arteries. Computerized image morphomelry was utilized to measure intimal and media! thickness and area. Rats receiving olive oil or CsA al 2.5 mg/kg/day had severe rejection and no graft survival. CsA at 5 mg/kg/day resulted in less severe rejection with significant intimal and medial proliferation (P < 0.001). CsA at 10-20 mg/kg/day paralleled Lewis-Lewis isograft outcomes and inhibited arteriosclerotic vascular changes in the allograft: (P < 0.001). Perivascular T-helper cells and macrophages were a characteristic finding with low-dose CsA but rare with higher CsA doses. In this new model of accelerated GCA in rats, immune-mediated antigen-dependent vasculopathy as a result of inadequate immunosuppresion is fundamental in the development of GCA, which appeared equally in epicardial arteries and intramyocardial arterioles. CsA prevents GCA in a dose-dependent fashion in the rat allograft.


Related Articles

  • Contribution of Proliferating Leukocytes to Phenotypic Change in Smooth Muscle Cells during the Development of Coronary Arteriosclerosis in Transplanted Hearts. Shirasawa, B.; Hamano, K.; Ueda, M.; Ito, H.; Kobayashi, T.; Fujimura, Y.; Kojima, A.; Esato, K. // European Surgical Research;2000, Vol. 32 Issue 1, p30 

    Background: It is well known that coronary arteriosclerosis after heart transplantation is concentric and rich in smooth muscle cells (SMCs); however, the role played by rejection in the intimal thickening caused by SMCs in coronary arteriosclerosis remains unclear. In this study, we examined...

  • Effects of Enalapril and L-158809 on Myocardial Beta-Adrenergic Receptor Density in Transplanted Rat Hearts. Nakame, T.; Iguchi, A.; Tabayashi, K. // European Surgical Research;2001, Vol. 33 Issue 4, p297 

    Background: We compare the effects of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II type 1 (AT[sub 1] ) receptor blocker on density of myocardial beta-adrenergic receptors (beta-ARs) in a heterotopic heart transplantation model. Methods: Hearts of F344 rats were heterotopically...

  • Unexpected Death in a Heart Transplant Recipient. Banet, Natalie; Gordon, Christopher; Willis, Monte; Gilligan, Peter; Thorne, Leigh // Laboratory Medicine;Jan2011, Vol. 42 Issue 1, p6 

    Patient: 55-year-old Hispanic male Chief Complaint: Three weeks pre-mortem: pleuritic chest pain, shortness of breath, and fatigue. History of Present Illness: The patient presented for routine monitoring of his heart transplant and complained of body weakness and positional chest discomfort. An...

  • Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial. Boissonnat, Pascale; Gaillard, S‚golŠne; Mercier, Catherine; Redonnet, Michel; Lelong, Bernard; Mattei, Marie-Fran‡oise; Mouly-Bandini, Annick; Pattier, Sabine; Sirinelli, AgnŠs; Epailly, Eric; Varnous, Shaida; Billes, Marc-Alain; Sebbag, Laurent; Ecochard, Ren‚; Cornu, Catherine; Gueyffier, Fran‡ois // Trials;2012, Vol. 13 Issue 1, p231 

    Background: Using reduced doses of Cyclosporine A immediately after heart transplantation in clinical trials may suggest benefits for renal function by reducing serum creatinine levels without a significant change in clinical endpoints. However, these trials were not sufficiently powered to...

  • Impact of Immunosuppressive Drugs on the Development of Cardiac Allograft Vasculopathy. Dandel, Michael; Hetzer, Roland // Current Vascular Pharmacology;Sep2010, Vol. 8 Issue 5, p706 

    No abstract available.

  • Repeated CMV Infection in a Heart Transplantation Patient. Melero-Ferrer, Josep; Sanchez-Lazaro, Ignacio J.; Navea-Tejerina, Amparo; Almenar-Bonet, Luis; Blanes-Julia, Marino; Martinez-Dolz, Luis; Salvador-Sanz, Antonio // Case Reports in Transplantation;2012, p1 

    Infections are one of the leading causes of morbidity and mortality in heart transplantation (HTx). Cytomegalovirus (CMV) is the most common viral infection during the first year after HTx, but it is more unusual after this time. We present the case of a patient who underwent an HTx due to a...

  • Early Sympathetic Reinnervation Demonstrated by Iodine-123 Metaiodobenzylguani- dine Imaging in a Child After Cardiac Transplantation. Watanabe, K.; Fukuchi, K.; Echigo, S. // Pediatric Cardiology;Sep/Oct2004, Vol. 25 Issue 5, p568 

    This article presents information on physiological changes undergone by a child after cardiac transplantation. In this context, a case study is being presented wherein a 2-year-old boy who underwent orthotopic cardiac transplantation because of dilated cardiomyopathy is being studied. It is...

  • Endothelial activation and development of coronary artery disease in transplanted human hearts. Labarrere, Carlos A.; Nelson, David R. // JAMA: Journal of the American Medical Association;10/08/97, Vol. 278 Issue 14, p1169 

    Presents a study to determine if early activation of arterial/arteriolar endothelium predicts the development of coronary artery disease, graft failure, or both in transplanted human hearts. Design and setting; Participants; Main outcome measures; Methods; Results; Conclusions.

  • Untitled. Smith, Jeanette M. // JAMA: Journal of the American Medical Association;3/09/94, Vol. 271 Issue 10, p730o 

    Presents an abstract of the article `Late Pathological Findings Following Cardiac Transplant: Review of 44 Autopsies Beyond Six Months Survival,' by R. Loire and others, which was lifted from a French cardiology journal. Anatomical lesion patterns; Graft coronary disease as an essential...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics