Key result
10 Gy total body irradiation in rats worsened lipid profiles (LDL 82 vs 13 mg/dl), injured coronary microvasculature, and reduced radial strain (19% vs 46%) compared to controls.
Why the study?
Does 10 Gy total body irradiation alter lipid profiles, coronary microvasculature, and ventricular function in a rat model?
Does 10 Gy total body irradiation alter lipid profiles, coronary microvasculature, and ventricular function in a rat model?
Total body irradiation, but not local thorax irradiation, induces significant coronary microvascular injury and ventricular dysfunction in rats, suggesting a role for non-thoracic circulating factors in radiation-induced heart disease.
Does not support changes to radiation protocols; leaves open whether circulating factors drive human radiation cardiotoxicity.
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.
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Baker et al. (2009) studied Radiation-induced injury. Total body irradiation (TBI) vs. Local thorax irradiation or non-irradiated controls was evaluated on Lipid profile, coronary microvasculature, and ventricular function. 10 Gy total body irradiation in rats worsened lipid profiles (LDL 82 vs 13 mg/dl), injured coronary microvasculature, and reduced radial strain (19% vs 46%) compared to controls.
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