Cardiovascular deconditioning during long-term spaceflight through multiscale modeling

Human spaceflight presents significant challenges to the cardiovascular system. Prolonged exposure to microgravity leads to cardiovascular deconditioning, characterized by fluid shifts, blood volume reduction, decreased cardiac muscle mass, and impaired exercise capacity. Understanding these changes is crucial for astronaut health and safety, particularly for long-duration missions to the Moon or Mars. Existing data on cardiovascular deconditioning are incomplete, inconsistent, and often limited to a few cardiac parameters due to the difficulties of performing clinical measurements in space. Ground-based analogs like bed rest and water immersion are not perfect representations of microgravity. Therefore, computational modeling offers a valuable approach to investigate the complex hemodynamic responses to microgravity. This study utilizes a validated 1D-0D multiscale model to comprehensively study cardiovascular response to long-term (at least 5 months) spaceflight, focusing on parameters not easily measured in vivo, such as right heart hemodynamics, oxygen consumption, and exercise tolerance. The model compares a 1G supine (reference baseline) condition to a long-term microgravity (0G) spaceflight condition, aiming to elucidate the underlying mechanisms and detailed hemodynamic changes.

The paper reviews over 50 studies on cardiovascular deconditioning during microgravity, prioritizing data from recent long-term spaceflights with routine countermeasures to establish a baseline. The review reveals inconsistencies and limitations in existing data, particularly regarding right heart hemodynamics, oxygen consumption, and exercise tolerance. The variability and often conflicting results are attributed to differences in baseline postures, crew characteristics, mission objectives, countermeasures employed, and mission durations. The authors highlight the existing literature's insufficiency to provide a complete picture of cardiovascular response in microgravity, underscoring the need for the computational approach presented in this paper.

A validated 1D-0D multiscale model of the cardiovascular system was employed. The model combines a 1D description of the arterial tree with a lumped-parameter (0D) representation of the venous return, heart chambers, pulmonary circulation, and baroreceptor regulation. The model has previously been validated against heart pacing and open-loop responses. The 1G supine condition served as the reference baseline. The 0G spaceflight condition was simulated by incorporating changes to model parameters based on a comprehensive literature review of long-term spaceflight data. These changes reflected the primary hemodynamic adjustments observed in microgravity, namely blood shift from lower to upper body, total blood volume reduction, reduced cardiac function and volume, increased lower extremity venous compliance, arterial resistance variations, and alterations in the baroreflex response. The model's output included time-series, average values, and waveform alterations of pressures, flow rates, and volumes in four cardiovascular regions (cerebral, cardio-thoracic, abdominal, and lower limbs). A new metric, Normalized Signal Difference (NSD), was introduced to quantify waveform alterations. Simulations were run until steady-state conditions were achieved. The model was validated a posteriori by comparing modeled cardiac parameters (e.g., stroke volume, cardiac output, mean arterial pressure) with available literature data from long-term spaceflights.

The model revealed a significant reduction in key cardiac parameters during simulated long-term spaceflight compared to the 1G supine condition. Cardiac work decreased by 19.29%, and oxygen consumption decreased by 1.91% (RPP) and 8.38% (TTI/min). Left ventricular contractility indices showed reductions (e.g., stroke volume -18.32%, ejection fraction -9.93%), consistent with literature data. Cardiac output decreased by 7.58% despite an increased heart rate (13%), reflecting a reduced stroke volume. Mean arterial pressure decreased by 9.92%, also agreeing with existing data. Analysis of pressure, flow rate, and volume time-series showed decreases in both mean pressure and flow rate across different regions. Pressure variations were relatively homogeneous (-8% to -12%), while flow rate changes were more heterogeneous, varying from -16% to -18% in the cerebral region to -2% to -6% in the lower limbs. The analysis of pulse pressure (PP) revealed high variability (+4.82% to -56%), and volume reductions were most pronounced in the lower limbs and abdomen. Waveform analysis using the NSD metric revealed significant alterations in pressure and flow rate signals, especially in the distal regions. Waveform changes were more pronounced for flow rate than pressure, and NSD values generally increased from proximal to distal regions. The study also examined the proximal-to-distal pathway of the arterial tree, showing that mean pressure changes remained fairly constant (-10%), while flow rate changes showed a non-uniform pattern, potentially due to resistance and compliance variations along the pathway. The overall findings suggest a state of cardiac deconditioning similar to that of an untrained person with a sedentary lifestyle. The key findings were validated by comparing modeled parameters with available in vivo measurements from long-term spaceflights.

The results demonstrate heterogeneous hemodynamic responses to microgravity. The combination of blood volume reduction and shift produced varying effects across the body. While blood shifted towards the upper body, this did not lead to increases in pressure and flow rate due to the interplay of resistance and compliance changes in different regions. The increased venous compliance in the legs helped mitigate pressure variations in the lower body. The smaller pressure variations in the venous compared to arterial regions are attributed to higher venous compliance. The high variability in pulse pressure and NSD emphasizes the heterogeneity of hemodynamic adjustments in different vascular districts. The increase of NSD towards distal regions suggests that the microgravity induced changes primarily affect peripheral regions where reflections from bifurcations and arteriolar interfaces modify the wave pattern, and this is worsened by the increased heart rate during spaceflight. While the changes observed in the simulated 0G steady-state are not dramatically severe in themselves, the condition becomes hazardous during re-entry or landing due to the backward blood shift, hypovolemic state, and reduced baroreceptor response, potentially causing orthostatic intolerance.

This study provides valuable insights into the complexities of cardiovascular deconditioning during long-term spaceflight using multiscale modeling. The model successfully predicted key hemodynamic changes and revealed significant waveform alterations, especially in distal regions. The findings underscore the importance of developing effective countermeasures for long space missions to mitigate cardiovascular risks associated with re-entry and gravity restoration. Future work could integrate different countermeasures into the model to evaluate their effectiveness and optimize strategies for maintaining cardiovascular health in space. The strong analogy between spaceflight deconditioning and sedentary aging suggests potential applications of these findings for improving our understanding of aging processes on Earth.

The model does not explicitly simulate interstitial fluid shifts. The effects of interstitial fluid shifts are implicitly considered by modifying the total and unstressed volumes of cardiovascular compartments. Although the model incorporates several aspects of cardiovascular deconditioning in microgravity, other factors like muscular atrophy and bone demineralization were not included, potentially underestimating the complexity of the overall physiological adaptation.