Long-term spaceflight and the cardiovascular system

Abstract

While early investigations into the physiological effects of spaceflight suggest the body's ability to reversibly adapt, the corresponding effects of long-term spaceflight (>6 months) are much less conclusive. Prolonged exposure to microgravity and radiation yields profound effects on the cardiovascular system, including a massive cephalad fluid translocation and altered arterial pressure, which attenuate blood pressure regulatory mechanisms and increase cardiac output. Also, central venous pressure decreases due to the loss of venous compression. The stimulation of baroreceptors by the cephalad shift results in an approximately 10–15% reduction in plasma volume, with fluid translocating from the vascular lumen to the interstitium. Despite possible increases in cardiac workload, myocyte atrophy and notable yet unexplained alterations in hematocrit have been observed. Atrophy is postulated to result from shunting of protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated action. While data are scarce regarding their causative agents, arrhythmias have been frequently reported, albeit sublethal, during both Russian and American expeditions, with QT interval prolongation observed in long, but not short duration, spaceflight. Exposure of the heart to the proton and heavy ion radiation of deep space has also been shown to result in coronary artery degeneration, aortic stiffness, carotid intima thickening via collagen-mediated action, accelerated atherosclerosis, and induction of a pro-inflammatory state. Upon return, long term spaceflight frequently results in orthostatic intolerance and altered sympathetic responses, which can prove hazardous should any rapid mobilization or evacuation be required, and indicates that these cardiac risks should be especially monitored for future missions.

Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration

“…Light ions primarily inhibit the early motile stages of micro-vessel formation, whereas heavy ions prevent the later stages of development, although they also act synergistically (Wuu et al, 2020). In small blood vessels, the inhibition of angiogenesis causes a gradual loss of vessels because of the lack of replacement of damaged vasculature (rarefaction), which leads to pathologies in the deprived tissues (Vernice et al, 2020). On an organismal level, rarefaction eventually causes pain in the extremities, high blood pressure, a longterm increase in the risk of hypertension, arterial thromboembolism, cardiac ischemia, and cardiac dysfunction (Abdel-Qadir et al, 2017).…”

Cell-free DNA (cfDNA) and Exosome Profiling from a Year-Long Human Spaceflight Reveals Circulating Biomarkers

“…It is also reported that active 20S proteasomes within apoptotic exosome-like vesicles can induce autoantibody production and accelerate organ rejection after transplantation ( Dieudé et al., 2015 ), reduce the amount of oligomerized proteins ( Schmidt et al., 2020 ) and reduce tissue damage after myocardial injury ( Lai et al., 2012 ), and are correlated with cancer and other pathological status such as viral infection and vascular injury ( Dieudé et al., 2015 ; Gunasekaran et al., 2020 ; Tugutova et al., 2019 ). The elevated circulating exosomal 20S proteasome in the flight subject may reflect the increased physiological need to clear these proteins resulting from long-term blood, immune, or other physiological disorders caused by various stress factors during the flight or return to gravity ( Ben-Nissan and Sharon, 2014 ; Vernice et al, 2020 ). Study of plasma exosomes obtained from flight subjects at other time points including pre- and inflight will be necessary to further examine whether plasma exosomal proteasome can serve as biomarkers for pathological processes associated with space flight.…”

Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart

“…Entering into microgravity causes a cephalad shift of body fluids which leads to increased heart stroke volume, a rise in left ventricular end diastolic dimensions and a fluid shift between the vasculature and interstitium [4][5][6]. The fluid shift invokes compensatory endocrine and renal mechanisms [6].…”