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


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.
Baker
John E
JE
Division of Cardiothoracic Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. jbaker@mcw.edu
Fish
Brian L
BL
Su
Jidong
J
Haworth
Steven T
ST
Strande
Jennifer L
JL
Komorowski
Richard A
RA
Migrino
Raymond Q
RQ
Doppalapudi
Anil
A
Harmann
Leanne
L
Allen Li
X
X
Hopewell
John W
JW
Moulder
John E
JE
D000818:Animals; D016026:Bone Marrow Transplantation; D003094:Collagen / Q000378:metabolism; D003324:Coronary Artery Disease / Q000150:complications / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005720:Gamma Rays / Q000009:adverse effects*; D006321:Heart / Q000503:physiopathology* / Q000528:radiation effects*; D008055:Lipids / Q000097:blood; D008297:Male; D009206:Myocardium / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000737:chemistry / Q000378:metabolism; D011829:Radiation Dosage; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000378:metabolism; D012307:Risk Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D008055:Lipids; D044463:Receptor, PAR-1; D005340:Fibrinogen; D003094:Collagen; D019001:Nitric Oxide Synthase