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

被引：93

作者：

Baker, John E. ^{[1
,2
,6
]}

Fish, Brian L. ^{[3
]}

Su, Jidong ^{[1
]}

Haworth, Steven T. ^{[4
]}

Strande, Jennifer L. ^{[4
,5
]}

Komorowski, Richard A. ^{[8
]}

Migrino, Raymond Q. ^{[5
]}

Doppalapudi, Anil ^{[4
]}

Harmann, Leanne ^{[4
]}

Li, X. Allen ^{[3
]}

Hopewell, John W. ^{[7
]}

Moulder, John E. ^{[3
]}

机构：

[1] Med Coll Wisconsin, Div Cardiothorac Surg, Milwaukee, WI 53226 USA

[2] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA

[3] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA

[4] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA

[5] Med Coll Wisconsin, Div Cardiovasc Med, Milwaukee, WI 53226 USA

[6] Childrens Hosp Wisconsin, Childrens Res Inst, Milwaukee, WI 53201 USA

[7] Churchill Hosp, Dept Clin Oncol, Oxford OX3 7LJ, England

[8] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA

来源：

INTERNATIONAL JOURNAL OF RADIATION BIOLOGY | 2009年 / 85卷 / 12期

基金：

美国国家卫生研究院;

关键词：

vascular sclerosis; blood lipids; ventricular function; total body irradiation; thorax only irradiation; morphology; cardiovascular risk factors; BONE-MARROW-TRANSPLANTATION; ATOMIC-BOMB SURVIVORS; II TYPE-2 RECEPTOR; RADIATION NEPHROPATHY; IONIZING-RADIATION; ANGIOTENSIN-II; CARDIOVASCULAR-DISEASE; STRAIN DIFFERENCES; X-IRRADIATION; CANCER;

D O I：

10.3109/09553000903264473

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (78 +/- 3 vs. 715 +/- 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.

引用

页码：1089 / 1100

页数：12