Numerical characterization of astronaut CaOx renal stone incidence rates to quantify in-flight and post-flight relative risk.

Changes in urine chemistry potentially alter the risk of renal stone formation in astronauts. Quantifying spaceflight renal stone incidence risk compared to pre-flight levels remains a significant challenge for assessing the appropriate vehicle, mission, and countermeasure design. A computational biochemistry model representing CaOx crystal precipitation, growth, and agglomeration is combined with a probabilistic analysis to predict the in- and post-flight CaOx renal stone incidence risk ratio (IRR) relative to pre-flight values using 1517 astronaut 24-h urine chemistries. Our simulations predict that in-flight fluid intake alone would need to increase from current prescriptions of 2.0-2.5 L/day to ~3.2 L/day to approach the CaOx IRR of the pre-flight population. Bone protective interventions would reduce CaOx risk to pre-flight levels if Ca excretion alone is reduced to <150 mg/day or if current levels are diminished to 190 mg/day in combination with increasing fluid intake to 2.5-2.7 L/day. This analysis provides a quantitative risk assessment that can influence the critical balance between engineering and astronaut health requirements.

Prediction of renal crystalline size distributions in space using a PBE analytic model. 2. Effect of dietary countermeasures.

An analytic Population Balance Equation model is used to assess the efficacy of citrate, pyrophosphate, and augmented fluid intake as dietary countermeasures aimed at reducing the risk of renal stone formation for astronauts. The model uses the measured biochemical profile of the astronauts as input and predicts the steady-state size distribution of the nucleating, growing, and agglomerating renal calculi subject to biochemical changes brought about by administration of these dietary countermeasures. Numerical predictions indicate that an increase in citrate levels beyond its average normal ground-based urinary values is beneficial but only to a limited extent. Unfortunately, results also indicate that any decline in the citrate levels during space travel below its normal urinary values on Earth can easily move the astronaut into the stone-forming risk category. Pyrophosphate is found to be an effective inhibitor since numerical predictions indicate that even at quite small urinary concentrations, it has the potential of shifting the maximum crystal aggregate size to a much smaller and plausibly safer range. Finally, our numerical results predict a decline in urinary volume below 1.5 liters/day can act as a dangerous promoter of renal stone development in microgravity while urinary volume levels of 2.5-3 liters/day can serve as effective space countermeasures.

Prediction of renal crystalline size distributions in space using a PBE analytic model. 1. Effect of microgravity-induced biochemical alterations.

An analytical Population Balance Equation model is developed and used to assess the risk of critical renal stone formation for astronauts during future space missions. The model uses the renal biochemical profile of the subject as input and predicts the steady-state size distribution of the nucleating, growing, and agglomerating calcium oxalate crystals during their transit through the kidney. The model is verified through comparison with published results of several crystallization experiments. Numerical results indicate that the model is successful in clearly distinguishing between 1-G normal and 1-G recurrent stone-former subjects based solely on their published 24-h urine biochemical profiles. Numerical case studies further show that the predicted renal calculi size distribution for a microgravity astronaut is closer to that of a recurrent stone former on Earth rather than to a normal subject in 1 G. This interestingly implies that the increase in renal stone risk level in microgravity is relatively more significant for a normal person than a stone former. However, numerical predictions still underscore that the stone-former subject carries by far the highest absolute risk of critical stone formation during space travel.

Impact of weightlessness on cardiac shape and left ventricular stress/strain distributions.

In this paper, a finite element model of the heart is developed to investigate the impact of different gravitational loadings of Earth, Mars, Moon, and microgravity on the cardiac shape and strain/stress distributions in the left ventricle. The finite element model is based on realistic 3D heart geometry, detailed fiber/sheet micro-architecture, and a validated orthotropic cardiac tissue model and constitutive relationship that capture the passive behavior of the heart at end-diastole. The model predicts the trend and magnitude of cardiac shape change at different gravitational levels with great fidelity in comparison to recent cardiac sphericity measurements performed during simulated reduced-gravity parabolic flight experiments. Moreover, the numerical predictions indicate that although the left ventricular strain distributions remain relatively unaltered across the gravitational fields and the strain extrema values occur at the same relative locations, their values change noticeably with decreasing gravity. As for the stress, however, both the magnitude and location of the extrema change with a decrease in the gravitational field. Consequently, tension regions of the heart on Earth can change into compression regions in space.

Open access integrated therapeutic and diagnostic platforms for personalized cardiovascular medicine.

It is undeniable that the increasing costs in healthcare are a concern. Although technological advancements have been made in healthcare systems, the return on investment made by governments and payers has been poor. The current model of care is unsustainable and is due for an upgrade. In developed nations, a law of diminishing returns has been noted in population health standards, whilst in the developing world, westernized chronic illnesses, such as diabetes and cardiovascular disease have become emerging problems. The reasons for these trends are complex, multifactorial and not easily reversed. Personalized medicine has the potential to have a significant impact on these issues, but for it to be truly successful, interdisciplinary mass collaboration is required. We propose here a vision for open-access advanced analytics for personalized cardiac diagnostics using imaging, electrocardiography and genomics.

Ventricular chamber sphericity during spaceflight and parabolic flight intervals of less than 1 G.

INTRODUCTION: Pathology driven alterations in the geometric shape of the heart have been found to result in regional changes in ventricular wall stress and a remodeling of the myocardium. If reductions in the gravitational forces acting on the heart produce similar changes in the overall contour of the ventricles, this modification might also induce adaptations in the cardiac structure during long-term spaceflight. In this study we examined the changes in left ventricle (LV) shape in spaceflight and during parabolic flights. METHODS: The diastole dimensions of the human LV were assessed with echocardiography during spaceflight and in parabolic flights which replicated the gravity of the Moon, Mars, and spaceflight and were compared to findings in Earth's gravity. LV dimensions were translated into circularity indices and geometric aspect ratios and correlated with their corresponding gravitational conditions. RESULTS: During parabolic flight, a linear relationship (r = 0.99) was found between both the circularity index and geometric aspect ratio values and the respective gravitational fields in which they were measured. During spaceflight (N = 4) and parabolic flights (N = 3), there was an average 4.1 and 4.4% higher circularity index and a 5.3 and 8.1% lower geometric aspect ratio, respectively. CONCLUSIONS: A correlative trend was found between the degree of LV sphericity and the amount of gravitational force directed caudal to the longitudinal orientation of the body. The importance of this finding is uncertain, but may have implications regarding physiologic adaptations in the myocardial structure secondary to changes in LV wall stress upon prolonged exposure to microgravity.

Incorporation of myofilament activation mechanics into a lumped model of the human heart.

The success and usefulness of lumped cardiovascular models are directly dependent on the physiological fidelity of their formulation. In most existing lumped formulations for the heart, the compliance of the chamber is modeled based on its electrical analog, the capacitor. This has traditionally resulted in the use of a pre-described time-varying stiffness modulus for simulating the cardiac contractions. Unfortunately, such a time-varying stiffness does not include any physiological contractile machinery and thus no dependency on fiber sarcomere length and intracellular calcium concentrations, key mechanisms responsible for proper cardiac function. In this paper a lumped cardiovascular model is presented that is based on the incorporation of detailed myofilament activation for simulating the ventricular calcium binding and cross-bridging mechanism. Upon validation against experimental data, it is shown that the new myofilament activation-based model considerably increases the physiological validity and internal consistency of the cardiovascular simulations in comparison to the traditional variable compliance-based models. It is also shown, through specific case studies, that the present model can serve as a quick response tool for testing various hypotheses concerning the impact of the calcium binding and crossbridge kinetics on the overall performance of the cardiovascular system.

Effect of gravity on the caloric stimulation of the inner ear.

Robert Barany won the 1914 Nobel Prize in medicine for his convection hypothesis for caloric stimulation. Microgravity caloric tests aboard the 1983 SpaceLab 1 mission produced nystagmus results that contradicted the basic premise of Barany's convection theory. In this paper, we present a fluid structural analysis of the caloric stimulation of the lateral semicircular canal. Direct numerical simulations indicate that on earth, natural convection is the dominant mechanism for endolymphatic flow. However, in the microgravity environment of orbiting spacecraft, where buoyancy effects are mitigated, an expansive convection becomes the sole mechanism for producing endolymph motion and cupular displacement. Transient 1 g and microgravity case studies are presented to delineate the different dynamic behaviors of the 1 g and microgravity endolymphatic flows. The associated fluid-structural interactions are also analyzed based on the time evolution of cupular displacements.

Ventless pressure control of two-phase propellant tanks in microgravity.

This work studies pressurization and pressure control of a large liquid hydrogen storage tank. A finite element model is developed that couples a lumped thermodynamic formulation for the vapor region with a complete solution of the Navier-Stokes and energy equations for the flow and temperature fields in the liquid. Numerical results show that buoyancy effects are strong, even in microgravity, and can reposition a vapor bubble that is initially at the center of the tank to a region near the tank wall in a relatively short time. Long-term tank pressurization with the vapor bubble at the tank wall shows that after an initial transient lasting about a week, the final rate of pressure increase agrees with a purely thermodynamic analysis of the entire tank. However, the final pressure levels are quite different from thermodynamic predictions. Numerical results also show that there is significant thermal stratification in the liquid due to the effects of natural convection. A subcooled jet is used to provide simultaneous cooling and mixing in order to bring the tank pressure back down to its initial value. Three different jet speeds are examined. Although the lowest jet speed is ineffective at controlling the pressure because of insufficient penetration into the liquid region, the highest jet speed is shown to be quite effective at disrupting thermal stratification and reducing the tank pressure in reasonable time.