Radiation-induced changes in the ultrastructure and mechanical function of the rat heart

Cilliers, G; Harper, Ian S.; Lochner, Amanda

doi:10.1016/0167-8140(89)90044-3

Cited by 37 publications

(16 citation statements)

References 18 publications

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“…During the intermediate phase, the influence of the heart irradiation disappeared (OR < 1). An explanation of this phenomenon may be derived from observations of early decline in cardiac function after heart irradiation followed by a period of recovery (likely coinciding with the intermediate phase) that precedes the onset of late symptoms reported for rats (43)(44)(45), dogs (38), and even humans (46,47). If true, this would change the traditional view of heart as a late-reacting organ and may bear relevance for clinical practice where the combination of subclinical injuries to lung and heart may give rise to unexpected toxicity, both early and late after the radiation treatment.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Radiation Injury: Identification of Risk Factors Associated with Regional Hypersensitivity

Novakova-Jiresova

Luijk

Goor³

et al. 2005

Cancer Research

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Effective radiation treatment of thoracic tumors is often limited by radiosensitivity of surrounding tissues. Several experimental studies have suggested variations in radiosensitivity of different pulmonary regions. Mice and rat studies in part contradict each other and urge for a more detailed analysis. This study was designed to obtain a more comprehensive insight in radiation injury development, expression, and its regional heterogeneity in lung. The latter is obviously highly critical for optimization of radiotherapy treatment plans and may shed light on the mechanisms of lung dysfunction after irradiation. Six different but volume-equal regions in rat lung were irradiated. Whereas the severity of damage, as seen in histologic analysis, was comparable in all regions, the degree of lung dysfunction, measured as breathing rates, largely varied. During the pneumonitic phase (early : 6-12 weeks), the most sensitive regions contained a substantial part of alveolar lung parenchyma. Also, a trend for hypersensitivity was observed when the heart lay in the irradiation field. In the fibrotic phase (late: 34-38 weeks), lung parenchyma and heartencompassing regions were the most sensitive. No impact of the heart was observed during the intermediate phase (16-28 weeks). The severity of respiratory dysfunction after partial thoracic irradiation is likely governed by an interaction between pulmonary and cardiac functional deficits. As a repercussion, more severe acute and delayed toxicity should be expected after combined lung and heart irradiation. This should be considered in the process of radiotherapy treatment planning of thoracic malignancies. (Cancer Res 2005; 65(9): 3568-76)

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Section: Discussionmentioning

confidence: 99%

Pulmonary Radiation Injury: Identification of Risk Factors Associated with Regional Hypersensitivity

Novakova-Jiresova

Luijk

Goor³

et al. 2005

Cancer Research

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“…In addition, mitochondria are sensitive to radiation and become a direct target of radiation damage within hours after exposure (12). Studies have shown that local heart irradiation can cause morphological damage in cardiac mitochondria (13, 14), and nontransient mitochondrial functional alterations including impairment of the respiratory chain and increased protein oxidation (15, 16). Irradiation has also been shown to increase the mitochondrial mass of certain cells in culture (17–19).…”

Section: Introductionmentioning

confidence: 99%

Radiation-Induced Alterations in Mitochondria of the Rat Heart

et al. 2014

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Radiation therapy for the treatment of thoracic cancers may be associated with radiation-induced heart disease (RIHD), especially in long-term cancer survivors. Mechanisms by which radiation causes heart disease are largely unknown. To identify potential long-term contributions of mitochondria in the development of radiation-induced heart disease, we examined the time course of effects of irradiation on cardiac mitochondria. In this study, Sprague-Dawley male rats received image-guided local X irradiation of the heart with a single dose ranging from 3–21 Gy. Two weeks after irradiation, left ventricular mitochondria were isolated to assess the dose-dependency of the mitochondrial permeability transition pore (mPTP) opening in a mitochondrial swelling assay. At time points from 6 h to 9 months after a cardiac dose of 21 Gy, the following analyses were performed: left ventricular Bax and Bcl-2 protein levels; apoptosis; mitochondrial inner membrane potential and mPTP opening; mitochondrial mass and expression of mitophagy mediators Parkin and PTEN induced putative kinase-1 (PINK-1); mitochondrial respiration and protein levels of succinate dehydrogenase A (SDHA); and the 70 kDa subunit of complex II. Local heart irradiation caused a prolonged increase in Bax/Bcl-2 ratio and induced apoptosis between 6 h and 2 weeks. The mitochondrial membrane potential was reduced until 2 weeks, and the calcium-induced mPTP opening was increased from 6 h up to 9 months. An increased mitochondrial mass together with unaltered levels of Parkin suggested that mitophagy did not occur. Lastly, we detected a significant decrease in succinate-driven state 2 respiration in isolated mitochondria from 2 weeks up to 9 months after irradiation, coinciding with reduced mitochondrial levels of succinate dehydrogenase A. Our results suggest that local heart irradiation induces long-term changes in cardiac mitochondrial membrane functions, levels of SDH and state 2 respiration. At any time after exposure to radiation, cardiac mitochondria are more prone to mPTP opening. Future studies will determine whether this makes the heart more susceptible to secondary stressors such as calcium overload or ischemia/reperfusion.

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“…Radiation either directly to the thorax or specifically to the heart (18,37,55,56,103,104) will result in the development of injury after doses of 15 Gy and higher. A single exposure to 15-60 Gy exerts an adverse long-term effect on cardiovascular function in the rat, resulting in morphological degeneration (53), mechanical dysfunction (98), damage to the endothelium (9), and increased mortality (56).…”

Section: Radiation As the Cause Of Late Cardiovascular Disease In Animentioning

confidence: 99%

Radiation as a Risk Factor for Cardiovascular Disease

Baker

Moulder

Hopewell

2011

Antioxidants & Redox Signaling

107

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Humans are continually exposed to ionizing radiation from terrestrial sources. The two major contributors to radiation exposure of the U.S. population are ubiquitous background radiation and medical exposure of patients. From the early 1980s to 2006, the average dose per individual in the United States for all sources of radiation increased by a factor of 1.7-6.2 mSv, with this increase due to the growth of medical imaging procedures. Radiation can place individuals at an increased risk of developing cardiovascular disease. Excess risk of cardiovascular disease occurs a long time after exposure to lower doses of radiation as demonstrated in Japanese atomic bomb survivors. This review examines sources of radiation (atomic bombs, radiation accidents, radiological terrorism, cancer treatment, space exploration, radiosurgery for cardiac arrhythmia, and computed tomography) and the risk for developing cardiovascular disease. The evidence presented suggests an association between cardiovascular disease and exposure to low-to-moderate levels of radiation, as well as the well-known association at high doses. Studies are needed to define the extent that diagnostic and therapeutic radiation results in increased risk factors for cardiovascular disease, to understand the mechanisms involved, and to develop strategies to mitigate or treat radiation-induced cardiovascular disease. Antioxid. Redox Signal. 15, 1945Signal. 15, -1956

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Radiation-induced changes in the ultrastructure and mechanical function of the rat heart

Cited by 37 publications

References 18 publications

Pulmonary Radiation Injury: Identification of Risk Factors Associated with Regional Hypersensitivity

Pulmonary Radiation Injury: Identification of Risk Factors Associated with Regional Hypersensitivity

Radiation-Induced Alterations in Mitochondria of the Rat Heart

Radiation as a Risk Factor for Cardiovascular Disease

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