10 Gy total body irradiation increases risk of coronary sclerosis, degeneration of heart structure and function in a rat model

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.

Keywords:

• vascular sclerosis
• blood lipids
• ventricular function
• total body irradiation
• thorax only irradiation
• morphology
• cardiovascular risk factors

Acknowledgements

The secretarial support of Mary Lynne Koenig, technical support of Eric Jensen, DVM, Mary Lou Mader and Amy Irving, Vladimir Semenko, PhD, for dosimetry studies and stimulating discussions with Eric P. Cohen, MD, are gratefully acknowledged. This work was presented in part at the 57th Annual Scientific Session meeting of the American College of Cardiology, 2008. This work was supported in part by cooperative agreement AI067734 and grants HL54075 and AI080363 from the National Institutes of Health.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.