Consequences of space radiation on the brain and cardiovascular system.

Staying longer in outer space will inevitably increase the health risks of astronauts due to the exposures to galactic cosmic rays and solar particle events. Exposure may pose a significant hazard to space flight crews not only during the mission but also later, when slow-developing adverse effects could finally become apparent. The body of literature examining ground-based outcomes in response to high-energy charged-particle radiation suggests differential effects in response to different particles and energies. Numerous animal and cellular models have repeatedly demonstrated the negative effects of high-energy charged-particle on the brain and cognitive function. However, research on the role of space radiation in potentiating cardiovascular dysfunction is still in its early stages. This review summarizes the available data from studies using ground-based animal models to evaluate the response of the brain and heart to the high-energy charged particles of GCR and SPE, addresses potential sex differences in these effects, and aims to highlight gaps in the current literature for future study.

Low- and moderate-dose non-cancer effects of ionizing radiation in directly exposed individuals, especially circulatory and ocular diseases: a review of the epidemiology.

PURPOSE: There are well-known correlations between high and moderate doses (>0.5 Gy) of ionizing radiation exposure and circulatory system damage, also between radiation and posterior subcapsular cataract. At lower dose correlations with circulatory disease are emerging in the Japanese atomic bomb survivors and in some occupationally exposed groups, and are still to some extent controversial. Heterogeneity in excess relative risks per unit dose in epidemiological studies at low (<0.1 Gy) and at low-moderate (>0.1 Gy, <0.5 Gy) doses may result from confounding and other types of bias, and effect modification by established risk factors. There is also accumulating evidence of excess cataract risks at lower dose and low dose rate in various cohorts. Other ocular endpoints, specifically glaucoma and macular degeneration have been little studied. In this paper, we review recent epidemiological findings, and also discuss some of the underlying radiobiology of these conditions. We briefly review some other types of mainly neurological nonmalignant disease in relation to radiation exposure. CONCLUSIONS: We document statistically significant excess risk of the major types of circulatory disease, specifically ischemic heart disease and stroke, in moderate- or low-dose exposed groups, with some not altogether consistent evidence suggesting dose-response non-linearity, particularly for stroke. However, the patterns of risk reported are not straightforward. We also document evidence of excess risks at lower doses/dose-rates of posterior subcapsular and cortical cataract in the Chernobyl liquidators, US Radiologic Technologists and Russian Mayak nuclear workers, with fundamentally linear dose-response. Nuclear cataracts are less radiogenic. For other ocular endpoints, specifically glaucoma and macular degeneration there is very little evidence of effects at low doses; radiation-associated glaucoma has been documented only for doses >5 Gy, and so has the characteristics of a tissue reaction. There is some evidence of neurological detriment following low-moderate dose (∼0.1-0.2 Gy) radiation exposure in utero or in early childhood.

Unchanged cardiovascular and respiratory outcomes in healthy C57Bl/6 mice after in utero exposure to ionizing radiation.

BACKGROUND: Advancements in medical technologies that utilize ionizing radiation have led to improved diagnosis and patient outcomes, however, the effect of ionizing radiation on the patient is still debated. In the case of pregnancy, the potential effects are not only to the mother but also to the fetus. The aim of this study was to determine if exposure from ionizing radiation during pregnancy alters the development of the cardiovascular and respiratory system of the offspring. MATERIALS AND METHODS: Pregnant C57Bl/6 mice were whole-body irradiated at gestational day 15 with a 137Cs gamma radiation emitting source at 0 mGy (sham), 50 mGy, 300 mGy, or 1000 mGy. Post weaning weight and blood pressure measurements were taken weekly for both male and female pups until euthanasia at 16-17 weeks postnatal age. Immediately following, the trachea was cannulated, and the lungs and heart excised. The lung was then examined to assess respiratory physiological outcomes. RESULTS AND CONCLUSIONS: In utero exposures to 1000 mGy caused significant growth reduction compared to sham irradiated, which remained persistent for both male and female pups. Growth restriction was not observed for lower exposures. There was no significant change in any cardiovascular or respiratory outcomes measured. Overall, intrauterine exposures to ionizing radiation does not appear to significantly alter the development of the cardiovascular and respiratory system in C57Bl/6 pups up to 17 weeks postnatal age.

Computational feasibility of simulating changes in blood flow through whole-organ vascular networks from radiation injury.

Vasculature is necessary to the healthy function of most tissues. In radiation therapy, injury of the vasculature can have both beneficial and detrimental effects, such as tumor starvation, cardiac fibrosis, and white-matter necrosis. These effects are caused by changes in blood flow due to the vascular injury. Previously, research has focused on simulating the radiation injury of vasculature in small volumes of tissue, ignoring the systemic effects of local damage on blood flow. Little is known about the computational feasibility of simulating the radiation injury to whole-organ vascular networks. The goal of this study was to test the computational feasibility of simulating the dose deposition to a whole-organ vascular network and the resulting change in blood flow. To do this, we developed an amorphous track-structure model to transport radiation and combined this with existing methods to model the vasculature and blood flow rates. We assessed the algorithm's computational scalability, execution time, and memory usage. The data demonstrated it is computationally feasible to calculate the radiation dose and resulting changes in blood flow from 2 million protons to a network comprising 8.5 billion blood vessels (approximately the number in the human brain) in 87 hours using a 128-node cluster. Furthermore, the algorithm demonstrated both strong and weak scalability, meaning that additional computational resources can reduce the execution time further. These results demonstrate, for the first time, that it is computationally feasible to calculate radiation dose deposition in whole-organ vascular networks. These findings provide key insights into the computational aspects of modeling whole-organ radiation damage. Modeling the effects radiation has on vasculature could prove useful in the study of radiation effects on tissues, organs, and organisms.

Evolving Role of Novel Quantitative PET Techniques to Detect Radiation-Induced Complications.

Radiation-induced normal tissue toxicities vary in terms of pathophysiologic determinants and timing of disease development, and they are influenced by the dose and radiation volume the critical organs receive, and the radiosensitivity of normal tissues and their baseline rate of cell turnover. Radiation-induced lung injury is dose limiting for the treatment of lung and thoracic cancers and can lead to fibrosis and potentially fatal pneumonitis. This article focuses on pulmonary and cardiovascular complications of radiation therapy and discusses how PET-based novel quantitative techniques can be used to detect these events earlier than current imaging modalities or clinical presentation allow.

[The reaction of the circulatory system to stress and electromagnetic fields emitted by mobile phones - 24-h monitoring of ECG and blood pressure]. / Reakcja ukladu krazenia na stres i pole elektromagnetyczne emitowane przez telefony komórkowe ­ 24-godzinne monitorowanie EKG i cisnienia tetniczego.

BACKGROUND: Experimental studies have shown cardiovascular effects of electromagnetic fields (EMF) emitted by mobile phones (e.g., prolonged QTc interval and abnormal blood pressure [BP] values). Also, stress may have an impact on the cardiovascular function. However, there are practically no data regarding the joint effect of exposure to stress and EMF, with both factors pertaining, e.g., to employees of mobile network operators. MATERIAL AND METHODS: Out of 208 subjects who had taken part in survey research, 55 workers agreed to undergo resting ECG, 24-h ECG and ambulatory blood pressure monitoring (ABPM). Their health condition, occupational and life-stress levels and EMF exposure were also assessed. RESULTS: Among the workers using mobile phones for more than 60 min daily, the systolic BP values in office measurement and at night-time in ABPM were significantly higher than among the workers spending less time talking on mobile phones (p = 0.04 and p = 0.036, respectively). The workers with the highest level of occupational stress showed significantly higher systolic 24-h BP (p = 0.007) and at day-time (p = 0.002), both during work (p = 0.010) and after work (p = 0.005), and higher diastolic BP values at day-time (p = 0.028). Cardiovascular response was strongly gender-related: males showed more BP abnormalities while females displayed more impairments in ECG records. The heart rate from 24 h was significantly correlated with the level of occupational stress, after adjusting for gender, life-stress and EMF. CONCLUSIONS: The findings obtained thus far have indicated the need to conduct in-depth studies on the impact of stress and EMF emitted by mobile phones on the health effects, in order to clarify the observed gender-related differences in cardiovascular response to the combined exposure to stress and EMF. Med Pr. 2019;70(4):411-24.

Cardiovascular effects of space radiation: implications for future human deep space exploration.

BACKGROUND: A manned mission to Mars has been contemplated by the world's largest space agencies for a number of years. The duration of the trip would necessitate a much longer exposure to deep space radiation than any human has ever been exposed to in the past. Concern regarding cancer risk has thus far stalled the progress of deep space exploration; however, the effect of space radiation on the cardiovascular system is significantly less well understood. DISCUSSION: Damage by radiation in space is mediated by a number of sources, including X-rays, protons and heavier charged atomic nuclei (HZE ions, the high-energy component of galactic cosmic rays). Previously, only lunar mission astronauts have been exposed to significant deep space radiation, with all other missions being low earth orbits only. The effect of this radiation on the human body has been inconclusively studied, and the long-term damage caused to the vascular endothelium by this radiation due to the effect of high-energy particles is not well known. CONCLUSION: Current radiation shielding technology, which would be viable for use in spacecraft, would not eliminate radiation risk. Similar to how a variety of shielding techniques are used every day by radiographers, again without full risk elimination, we need to explore and better understand the effect of deep space radiation in order to ensure the safety of those on future space missions.

GeneLab Database Analyses Suggest Long-Term Impact of Space Radiation on the Cardiovascular System by the Activation of FYN Through Reactive Oxygen Species.

Space radiation has recently been considered a risk factor for astronauts' cardiac health. As an example, for the case of how to query and identify datasets within NASA's GeneLab database and demonstrate the database utility, we used an unbiased systems biology method for identifying key genes/drivers for the contribution of space radiation on the cardiovascular system. This knowledge can contribute to designing appropriate experiments targeting these specific pathways. Microarray data from cardiomyocytes of male C57BL/6 mice followed-up for 28 days after exposure to 900 mGy of 1 GeV proton or 150 mGy of 1 GeV/n 56Fe were compared to human endothelial cells (HUVECs) cultured for 7 days on the International Space Station (ISS). We observed common molecular pathways between simulated space radiation and HUVECs flown on the ISS. The analysis suggests FYN is the central driver/hub for the cardiovascular response to space radiation: the known oxidative stress induced immediately following radiation would only be transient and would upregulate FYN, which in turn would reduce reactive oxygen species (ROS) levels, protecting the cardiovascular system. The transcriptomic signature of exposure to protons was also much closer to the spaceflight signature than 56Fe's signature. To our knowledge, this is the first time GeneLab datasets were utilized to provide potential biological indications that the majority of ions on the ISS are protons, clearly illustrating the power of omics analysis. More generally, this work also demonstrates how to combine animal radiation studies done on the ground and spaceflight studies to evaluate human risk in space.

Early Changes in Cardiovascular Biomarkers with Contemporary Thoracic Radiation Therapy for Breast Cancer, Lung Cancer, and Lymphoma.

PURPOSE: We characterized the early changes in cardiovascular biomarkers with contemporary thoracic radiation therapy (RT) and evaluated their associations with radiation dose-volume metrics including mean heart dose (MHD), V5, and V30. METHODS AND MATERIALS: In a prospective longitudinal study of 87 patients with breast cancer, lung cancer, or mediastinal lymphoma treated with photon or proton thoracic RT, blood samples were obtained pre-RT and after completion of RT (median, 20 days; interquartile range [IQR], 1-35). High-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, placental growth factor (PIGF), and growth differentiation factor 15 (GDF-15) were measured. Associations between MHD, V5 and V30, and biomarker levels and associations between echocardiography-derived measures of cardiac function and biomarker levels were assessed in multivariable linear regression models. Analyses were performed according to the following subgroups: (1) breast cancer alone and (2) lung cancer and lymphoma combined. RESULTS: The median (IQR) estimates of MHD ranged from 1.3 Gy (0.9-2.4) in breast cancer (n = 60) to 6.8 Gy (5.4-10.2) in mediastinal lymphoma (n = 14) and 8.4 Gy (6.7-16.1) in lung cancer (n = 13) patients (P < .001). There were no significant increases in biomarker levels from pre-RT to post-RT in breast cancer. In lung cancer/lymphoma, PIGF increased from a median (IQR) of 20 ng/L (16-26) to 22 ng/L (16-30) (P = .005), and GDF-15 increased from 1171 ng/L (755-2493) to 1887 ng/L (903-3763) (P = .006). MHD, V5, and V30 were significantly associated with post-RT PIGF and GDF-15 levels in multivariable models. Changes in biomarkers were not significantly associated with changes in echocardiography-derived measures of cardiac function. CONCLUSION: Contemporary thoracic RT induces acute abnormalities in vascular and inflammatory biomarkers that are associated with radiation dose-volume metrics, particularly in lung cancer and mediastinal lymphoma. Long-term follow-up studies are needed to determine the impact of these changes on the development of overt cardiac disease.

Cardiovascular Toxicities of Radiation Therapy.

As cancer survival outcomes improve, there is a growing focus on survivorship and long-term morbidity after cancer treatment. In particular, there has been concern about the long-term effects of radiotherapy on cardiac function. In this review, we discuss the cardiac effects of radiotherapy in the context of potential confounding factors, examine the potential parameters of interest when studying and modeling cardiac injury, highlight current treatment techniques to minimize radiation to the heart, and consider future areas of improvement and study.

Multi-Modality Imaging in the Assessment of Cardiovascular Toxicity in the Cancer Patient.

Cancer therapy can be associated with both cardiac and vascular toxicity. Advanced multi-modality imaging can be used to stratify patient risk, identify cardiovascular injury during and after therapy, and forecast recovery. Echocardiography continues to be the mainstay in the evaluation of cardiac toxicity. Particularly, echocardiography-based strain imaging is useful for risk stratification of patients at baseline, and detection of subclinical left ventricle (LV) dysfunction during therapy. Cardiac magnetic resonance (CMR) serves a complementary role in the patient with poor echocardiographic or equilibrium radionuclide angiographic image quality or in situations where a more accurate and precise LV ejection fraction measurement is needed to inform decisions regarding discontinuation of chemotherapy. New CMR techniques like T1 and T2 mapping and positron emission tomography (PET) imaging will help us better understand the structural, pathological, and metabolic myocardial changes associated with ventricular dysfunction or release of serum biomarkers. CMR may also be helpful in the evaluation of vascular complications of cancer therapy. Stress echocardiography, stress CMR, computed tomography, and PET are excellent imaging options in the evaluation of ischemia in patients receiving therapies that could potentially cause vasospasm or accelerated atherosclerosis.

Heart in space: effect of the extraterrestrial environment on the cardiovascular system.

National space agencies and private corporations aim at an extended presence of humans in space in the medium to long term. Together with currently suboptimal technology, microgravity and cosmic rays raise health concerns about deep-space exploration missions. Both of these physical factors affect the cardiovascular system, whose gravity-dependence is pronounced. Heart and vascular function are, therefore, susceptible to substantial changes in weightlessness. The altered cardiovascular function in space causes physiological problems in the postflight period. A compromised cardiovascular system can be excessively vulnerable to space radiation, synergistically resulting in increased damage. The space radiation dose is significantly lower than in patients undergoing radiotherapy, in whom cardiac damage is well-documented following cancer therapy in the thoracic region. Nevertheless, epidemiological findings suggest an increased risk of late cardiovascular disease even with low doses of radiation. Moreover, the peculiar biological effectiveness of heavy ions in cosmic rays might increase this risk substantially. However, whether radiation-induced cardiovascular effects have a threshold at low doses is still unclear. The main countermeasures to mitigate the effect of the space environment on cardiac function are physical exercise, antioxidants, nutraceuticals, and radiation shielding.

Impact of Ionizing Radiation on the Cardiovascular System: A Review.

Radiation therapy has become one of the main forms of treatment for various types of cancers. Cancer patients previously treated with high doses of radiation are at a greater risk to develop cardiovascular complications later in life. The heart can receive varying doses of radiation depending on the type of therapy and can even reach doses in the range of 17 Gy. Multiple studies have highlighted the role of oxidative stress and inflammation in radiation-induced cardiovascular damage. Doses of ionizing radiation below 200 mGy, however, have been shown to have beneficial effects in some experimental models of radiation-induced damage, but low-dose effects in the heart is still debated. Low-dose radiation may promote heart health and reduce damage from oxidative stress and inflammation, however there are few studies focusing on the impact of low-dose radiation on the heart. In this review, we summarize recent studies from animal models and human data focusing on the effects and mechanism(s) of action of radiation-induced damage to the heart, as well as the effects of high and low doses of radiation and dose rates.

Out of the frying pan and into the fire: damage-associated molecular patterns and cardiovascular toxicity following cancer therapy.

Cardio-oncology is a new and rapidly expanding field that merges cancer and cardiovascular disease. Cardiovascular disease is an omnipresent side effect of cancer therapy; in fact, it is the second leading cause of death in cancer survivors after recurrent cancer. It has been well documented that many cancer chemotherapeutic agents cause cardiovascular toxicity. Nonetheless, the underlying cause of cancer therapy-induced cardiovascular toxicity is largely unknown. In this review, we discuss the potential role of damage-associated molecular patterns (DAMPs) as an underlying contributor to cancer therapy-induced cardiovascular toxicity. With an increasing number of cancer patients, as well as extended life expectancy, understanding the mechanisms underlying cancer therapy-induced cardiovascular disease is of the utmost importance to ensure that cancer is the only disease burden that cancer survivors have to endure.

Biological effects and mechanisms of shortwave radiation: a review.

With the increasing knowledge of shortwave radiation, it is widely used in wireless communications, radar observations, industrial manufacturing, and medical treatments. Despite of the benefits from shortwave, these wide applications expose humans to the risk of shortwave electromagnetic radiation, which is alleged to cause potential damage to biological systems. This review focused on the exposure to shortwave electromagnetic radiation, considering in vitro, in vivo and epidemiological results that have provided insight into the biological effects and mechanisms of shortwave. Additionally, some protective measures and suggestions are discussed here in the hope of obtaining more benefits from shortwave with fewer health risks.

Radiobiology in Cardiovascular Imaging.

The introduction of ionizing radiation in medicine revolutionized the diagnosis and treatment of disease and dramatically improved and continues to improve the quality of health care. Cardiovascular imaging and medical imaging in general, however, are associated with a range of radiobiologic effects, including, in rare instances, moderate to severe skin damage resulting from cardiac fluoroscopy. For the dose range associated with diagnostic imaging (corresponding to effective doses on the order of 10 mSv [1 rem]), the possible effects are stochastic in nature and largely theoretical. The most notable of these effects, of course, is the possible increase in cancer risk. The current review addresses radiobiology relevant to cardiovascular imaging, with particular emphasis on radiation induction of cancer, including consideration of the linear nonthreshold dose-response model and of alternative models such as radiation hormesis.

[Preventing cardiovascular risk in miners].

The article presents results concerning usage of intravenous laser radiation of blood in miners with cardiovascular diseases. After cardiovascular state assessment, the miners at high cardiovascular risk were subjected to prophylactic procedures with traditional medical treatment added by intravenous laser therapy. Findings are anti-arrhythmic, antihypertensive, antiatherogenic and anti-aggregation effects of complex treatment with intravenous laser radiation of blood in miners at high cardiovascular risk and its subsequent decrease due to treatment.

Cardiovascular effects of radiotherapy on the patient with cancer.

The incidence of cancer (CA) has increased globally and radiotherapy (RT) is a vital component in its treatment. Cardiovascular injuries induced by RT in the treatment of thoracic and cervical CA have been causing problems in clinical practice for decades, and are among the most serious adverse effects of radiation experienced by the growing number of cancer survivors. This article presentes a review on the Lilacs, Scielo and Pubmed databases of the main cardiovascular injuries, their mechanisms, clinical presentations, treatments and prevention proposals. Injuries caused by RT include diseases of the pericardium, coronary artery disease, valvular disease, myocardial disease with systolic and diastolic dysfunction, conduction disorders, and carotid artery and great vessels disease. Thoracic and cervical irradiation increases cardiovascular morbidity and mortality. Despite the great progress in the improvement of RT techniques, totally excluding prime areas of the cardiovascular system from the irradiation field is not yet possible. Guidelines must be created for monitoring, diagnosis and treatment of patients with CA treated with RT.

Cardiovascular effects of radiotherapy on the patient with cancer / Efeitos cardiovasculares da radioterapia no paciente com câncer

Summary The incidence of cancer (CA) has increased globally and radiotherapy (RT) is a vital component in its treatment. Cardiovascular injuries induced by RT in the treatment of thoracic and cervical CA have been causing problems in clinical practice for decades, and are among the most serious adverse effects of radiation experienced by the growing number of cancer survivors. This article presentes a review on the Lilacs, Scielo and Pubmed databases of the main cardiovascular injuries, their mechanisms, clinical presentations, treatments and prevention proposals. Injuries caused by RT include diseases of the pericardium, coronary artery disease, valvular disease, myocardial disease with systolic and diastolic dysfunction, conduction disorders, and carotid artery and great vessels disease. Thoracic and cervical irradiation increases cardiovascular morbidity and mortality. Despite the great progress in the improvement of RT techniques, totally excluding prime areas of the cardiovascular system from the irradiation field is not yet possible. Guidelines must be created for monitoring, diagnosis and treatment of patients with CA treated with RT.

Resumo A incidência de câncer (CA) tem aumentado globalmente e a radioterapia (RT) é um componente vital do tratamento. As lesões cardiovasculares induzidas pela RT no tratamento de CA torácicos e cervicais geram problemas à prática clínica há décadas e estão entre os efeitos adversos mais graves da RT experimentados pelo crescente número de sobreviventes de CA. Neste artigo, realiza-se revisão nas bases Lilacs, Scielo e Pubmed das principais lesões cardiovasculares secundárias à RT, os mecanismos fisiopatológicos, as apresentações clínicas, os tratamentos e as propostas de prevenção. Dentre as lesões pela RT, destacam-se as doenças do pericárdio, a doença arterial coronariana, a doença valvular, a doença do miocárdio com disfunção sistólica e diastólica, os distúrbios de condução, a doença das artérias carótidas e dos grandes vasos. A irradiação torácica e cervical aumentam a morbimortalidade cardiovascular. Apesar da grande evolução no aprimoramento das técnicas de RT, ainda não foi possível excluir totalmente áreas nobres do sistema cardiovascular dos campos de irradiação. Faz-se necessária a instituição de diretrizes para monitoramento, diagnóstico e tratamento dos pacientes com CA submetidos à RT.

Radiation Toxicity to the Cardiovascular System.

Radiation therapy is an important component of cancer treatment, and today, it is applied to approximately 50% of malignancies, including valvular, myocardial, pericardial, coronary or peripheral vascular disease, and arrhythmias. An increased clinical suspicion and knowledge of those mechanisms is important to initiate appropriate screening for the optimal diagnosis and treatment. As the number of cancer survivors has been steadily increasing over the last decades, cardio-oncology, an evolving subspecialty of cardiology, will soon play a pivotal role in raising awareness of the increased cardiovascular risk and formulate strategies to optimally manage patients in this unique population.