## 1 Introduction
### Effects on the Cardiovascular System  
During short-duration spaceflight, microgravity alters cardiovascular physiology by reducing circulatory blood volume, diastolic blood pressure, left ventricular mass, and cardiac contractility [42; 123]. Several studies have demonstrated that peak exercise performance is reduced both inflight and immediately after short-duration spaceflight due primarily to a reduction in maximal cardiac output and O\({}_{2}\) delivery [124; 125]. Prolonged exposure to microgravity does cause unloading of the cardiovascular system (e.g., removal of expected loading effects from Earth's gravity when upright during the day), resulting in cardiac atrophy. These changes may be an example of adaptive physiologic changes (\"physiologic atrophy\") that returns to baseline after returning from spaceflight. This process may be similar to the adaptive physiologic changes to the cardiovascular system seen during athletic training (\"physiologic hypertrophy\"). Thus far, there is no evidence that the observed short-term cardiac atrophy could permanently impair systolic function. However, this physiologic adaptation to microgravity in space could lead to orthostatic hypotension/intolerance upon returning to Earth's gravity due to changes in the comparative position of peripheral resistance and sympathetic nerve activity [41; 126; 127]. Figure 1 demonstrates potential effects of the space environment on each organ system. Another potential effect of microgravity exposure is that an alteration of hydrostatic forces in the vertical gravitational (Gz) axis could lead to the formation of internal jugular vein thromboses [28; 29]. Anticoagulation would not be an ideal choice for prevention  
Figure 1: Potential effects of the space environment on each organ system. as astronauts have an increased risk of suffering traumatic injury during spaceflight, thus potentially inflating the risk of developing an intracerebral hemorrhage or subdural hematoma. In addition, if a traumatic accident were to occur during spaceflight, the previously discussed cardiovascular adaptations could impair the body's ability to tolerate blood loss and shock [45; 46; 47]. During long-duration spaceflight, one recent study demonstrated that astronauts did not experience orthostatic hypotension/intolerance during routine activities or after landing following 6 months in space [128]. It is worth noting that all of these astronauts performed aggressive exercise countermeasures while in flight [128]. Another study of healthy astronauts after 6 months of space travel showed that the space environment caused transient changes in left atrial structure/electrophysiology, increasing the risk of developing atrial fibrillation (AF) [129]. However, there was no definitive evidence of increased incidence of supraventricular arrhythmias and no identified episodes of AF [129]. Evaluation with echocardiography or cardiac MRI may be considered following long-duration spaceflight in certain cases. Prior human studies with supplemental data obtained from animal studies, have shown that healthy individuals with prolonged exposure to ionizing radiation may be at increased risk for the development of accelerated atherosclerosis secondary to radiation-induced endothelial damage and a subsequent pro-inflammatory response [3; 4; 57; 58; 59; 60; 123]. One study utilizing human 3D micro-vessel models showed that ionizing radiation inhibits angiogenesis via mechanisms dependent on the linear energy transfer (LET) of charged particles [130], which could eventually lead to cardiac dysfunction [131; 132]. In fact, specific characteristics of the radiation encountered in space may be an important factor to understanding its effects. For example, studies of pediatric patients undergoing radiotherapy have shown an increase in cardiac-related morbidity/mortality due to radiation exposure, but not until radiation doses exceeded 10 Gy [133].