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Late Effects of Total-Body Gamma Irradiation on Cardiac Structure and Function in Male Rhesus Macaques.

  • Academic Journal
  • DeBo RJ; Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
    Lees CJ; Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
    Dugan GO; Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
    Caudell DL; Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
    Michalson KT; Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
    Hanbury DB; Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
    Kavanagh K; Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
    Cline JM; Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
    Register TC; Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
  • Radiation research [Radiat Res] 2016 Jul; Vol. 186 (1), pp. 55-64. Date of Electronic Publication: 2016 Jun 22.
  • English
  • Heart disease is an increasingly recognized, serious late effect of radiation exposure, most notably among breast cancer and Hodgkin's disease survivors, as well as the Hiroshima and Nagasaki atomic bomb survivors. The purpose of this study was to evaluate the late effects of total-body irradiation (TBI) on cardiac morphology, function and selected circulating biomarkers in a well-established nonhuman primate model. For this study we used male rhesus macaques that were exposed to a single total-body dose of ionizing gamma radiation (6.5-8.4 Gy) 5.6-9.7 years earlier at ages ranging from ∼3-10 years old and a cohort of nonirradiated controls. Transthoracic echocardiography was performed annually for 3 years on 20 irradiated and 11 control animals. Myocardium was examined grossly and histologically, and myocardial fibrosis/collagen was assessed microscopically and by morphometric analysis of Masson's trichrome-stained sections. Serum/plasma from 27 irradiated and 13 control animals was evaluated for circulating biomarkers of cardiac damage [N-terminal pro B-type natriuretic protein (nt-proBNP) and troponin-I], inflammation (CRP, IL-6, MCP-1, sICAM) and microbial translocation [LPS-binding protein (LBP) and sCD14]. A higher prevalence of histological myocardial fibrosis was observed in the hearts obtained from the irradiated animals (9/14) relative to controls (0/3) (P = 0.04, χ(2)). Echocardiographically determined left ventricular end diastolic and systolic diameters were significantly smaller in irradiated animals (repeated measures ANOVA, P < 0.001 and P < 0.008, respectively). Histomorphometric analysis of trichrome-stained sections of heart tissue demonstrated ∼14.9 ± 1.4% (mean ± SEM) of myocardial area staining for collagen in irradiated animals compared to 9.1 ± 0.9 % in control animals. Circulating levels of MCP-1 and LBP were significantly higher in irradiated animals (P < 0.05). A high incidence of diabetes in the irradiated animals was associated with higher plasma triglyceride and lower HDLc but did not appear to be associated with cardiovascular phenotypes. These results demonstrate that single total-body doses of 6.5-8.4 Gy produced long-term effects including a high incidence of myocardial fibrosis, reduced left ventricular diameter and elevated systemic inflammation. Additional prospective studies are required to define the time course and mechanisms underlying radiation-induced heart disease in this model.
Additional Information
Publisher: Radiation Research Society Country of Publication: United States NLM ID: 0401245 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1938-5404 (Electronic) Linking ISSN: 00337587 NLM ISO Abbreviation: Radiat Res Subsets: MEDLINE
Publication: Bozeman, MT : Radiation Research Society
Original Publication: Charlottesville, VA : Kluge Carden Jennnings Pub. Co.
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U19 AI067798 United States AI NIAID NIH HHS
0 (Biomarkers)
0 (Lipids)
Date Created: 20160623 Date Completed: 20170525 Latest Revision: 20220408
20221216
PMC5068576
10.1667/RR14357.1
27333082
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