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10 Gy total body irradiation increases risk of coronary sclerosis, degeneration of heart structure and function in a rat model. Int J Radiat Biol 2009 Dec;85(12):1089-100

Date

12/10/2009

Pubmed ID

19995235

Pubmed Central ID

PMC2792125

DOI

10.3109/09553000903264473

Scopus ID

2-s2.0-72049116047   67 Citations

Abstract

PURPOSE: To determine the impact of 10 Gy total body irradiation (TBI) or local thorax irradiation, a dose relevant to a radiological terrorist threat, on lipid and liver profile, coronary microvasculature and ventricular function.

MATERIALS AND METHODS: WAG/RijCmcr rats received 10 Gy TBI followed by bone marrow transplantation, or 10 Gy local thorax irradiation. Age-matched, non-irradiated rats served as controls. The lipid profile and liver enzymes, coronary vessel morphology, nitric oxide synthase (NOS) isoforms, protease activated receptor (PAR)-1 expression and fibrinogen levels were compared. Two-dimensional strain echocardiography assessed global radial and circumferential strain on the heart.

RESULTS: TBI resulted in a sustained increase in total and low density lipoprotein (LDL) cholesterol (190 +/- 8 vs. 58 +/- 6; 82 +/- 8 vs. 13 +/- 3 mg/dl, respectively). The density of small coronary arterioles was decreased by 32%. Histology revealed complete blockage of some vessels while cardiomyocytes remained normal. TBI resulted in cellular peri-arterial fibrosis whereas control hearts had symmetrical penetrating vessels with less collagen and fibroblasts. TBI resulted in a 32 +/- 4% and 28 +/- 3% decrease in endothelial NOS and inducible NOS protein, respectively, and a 21 +/- 4% and 35 +/- 5% increase in fibrinogen and PAR-1 protein respectively, after 120 days. TBI reduced radial strain (19 +/- 8 vs. 46 +/- 7%) and circumferential strain (-8 +/- 3 vs. -15 +/- 3%) compared to controls. Thorax-only irradiation produced no changes over the same time frame.

CONCLUSIONS: TBI with 10 Gy, a dose relevant to radiological terrorist threats, worsened lipid profile, injured coronary microvasculature, altered endothelial physiology and myocardial mechanics. These changes were not manifest with local thorax irradiation. Non-thoracic circulating factors may be promoting radiation-induced injury to the heart.

Author List

Baker JE, Fish BL, Su J, Haworth ST, Strande JL, Komorowski RA, Migrino RQ, Doppalapudi A, Harmann L, Allen Li X, Hopewell JW, Moulder JE

Author

John E. Baker PhD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Bone Marrow Transplantation
Collagen
Coronary Artery Disease
Disease Models, Animal
Fibrinogen
Fibroblasts
Gamma Rays
Heart
Lipids
Male
Myocardium
Nitric Oxide Synthase
Radiation Dosage
Rats
Rats, Wistar
Receptor, PAR-1
Risk Factors
Whole-Body Irradiation
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a