Evaluation of the Spaceflight Cardiovascular Disease Risk Using the Clinical Prediction Model Astro-CHARM and the NASA Radiation Risk Model
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Ianik Plante↗
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Computer simulation of cardiovascular changes during extended duration space flights
The application of mathematical modeling and computer simulation to the study of spaceflight cardiovascular changes is examined using a multicompartment representation model of the entire human cardiovascular system including its control elements. The model simulates the beat-to-beat dynamic responses of the cardiovascular system to orthostatic stresses. Simulation results pertaining to long-term space flight, the combined effect of +G(z) and blood volume loss, and the effect of anti-G suit inflation are discussed, including past results on the original version of the model which has been used in a number of analysis applications at NASA. New results pertain to analysis of cardiovascular changes in extended duration space flights and demonstrate the use of this model in evaluation of physiological factors that contribute to orthostatic intolerance following an exposure to weightlessness, in particular, blood volume loss and changes in the sensitivity of baroreceptors.
Srinivasan, R. Srini↗
Image-Based Computational Fluid Dynamics in Blood Vessel Models: Toward Developing a Prognostic Tool to Assess Cardiovascular Function Changes in Prolonged Space Flights
One of NASA's objectives is to be able to perform a complete, pre-flight, evaluation of cardiovascular changes in astronauts scheduled for prolonged space missions. Computational fluid dynamics (CFD) has shown promise as a method for estimating cardiovascular function during reduced gravity conditions. For this purpose, MRI can provide geometrical information, to reconstruct vessel geometries, and measure all spatial velocity components, providing location specific boundary conditions. The objective of this study was to investigate the reliability of MRI-based model reconstruction and measured boundary conditions for CFD simulations. An aortic arch model and a carotid bifurcation model were scanned in a 1.5T Siemens MRI scanner. Axial MRI acquisitions provided images for geometry reconstruction (slice thickness 3 and 5 mm; pixel size 1x1 and 0.5x0.5 square millimeters). Velocity acquisitions provided measured inlet boundary conditions and localized three-directional steady-flow velocity data (0.7-3.0 L/min). The vessel walls were isolated using NIH provided software (ImageJ) and lofted to form the geometric surface. Constructed and idealized geometries were imported into a commercial CFD code for meshing and simulation. Contour and vector plots of the velocity showed identical features between the MRI velocity data, the MRI-based CFD data, and the idealized-geometry CFD data, with less than 10% differences in the local velocity values. CFD results on models reconstructed from different MRI resolution settings showed insignificant differences (less than 5%). This study illustrated, quantitatively, that reliable CFD simulations can be performed with MRI reconstructed models and gives evidence that a future, subject-specific, computational evaluation of the cardiovascular system alteration during space travel is feasible.
Chatzimavroudis, George P.↗
Characterization of fluid physics effects on cardiovascular response to microgravity (G-572)
The investigation of cardiovascular adaptation to space flight has seen substantial advancement in the last several years. In-flight echocardiographic measurements of astronaut cardiac function on the Space Shuttle have documented an initial increase, followed by a progressive reduction in both left ventricular volume index and stroke volume with a compensatory increase in heart rate to maintain cardiac output. To date, the reduced cardiac size and stroke volume have been presumed to be the consequence of the reduction in circulating fluid volume within a few days after orbital insertion. However, no specific mechanism for the reduced stroke volume has been identified. The following investigation proposes the use of a hydraulic model of the cardiovascular system to examine the possibility that the observed reduction in stroke volume may, in part, be related to fluid physics effects on heart function. The automated model is being prepared to fly as a Get Away Special (GAS) payload within the next year.
Pantalos, George M.↗
Characterization of fluid physics effects on cardiovascular response to microgravity (G-572)
The recognition and understanding of cardiovascular adaptation to spaceflight has experienced substantial advancement in the last several years. In-flight echocardiographic measurements of astronaut cardiac function on the Space Shuttle have documented a 15 percent reduction in both left ventricular volume index and stroke volume with a compensatory increase in heart rate to maintain cardiac output. To date, the reduced cardiac size and stroke volume have been presumed to be the consequence of the reduction in circulating fluid volume following diuresis and other physiological processes to reduce blood volume within a few days after orbital insertion. However, no specific mechanism for the reduced stroke volume has been elucidated. The following investigation proposes the use of a hydraulic model of the cardiovascular system to examine the possibility that the observed reduction in stroke volume may, in part, be related to fluid physics effects on heart function. The automated model is being prepared to fly as a GAS payload. The experimental apparatus consists of a pneumatically actuated, elliptical artificial ventricle connected to a closed-loop, hydraulic circuit with compliance and resistance elements to create physiologic pressure and flow conditions. The ventricle is instrumented with high-fidelity, acceleration-insensitive, catheter-tip pressure transducers (Millar Instruments) in the apex and base to determine the instantaneous ventricular pressures and (delta)P(sub LV) across the left ventricle (LVP(sub apex)-LVP(sub base). The ventricle is also instrumented with a flow probe and pressure transducers immediately upstream of the inflow valve and downstream of the outflow valve. The experiment will be microprocessor controlled with analog signals stored on the FM data tape recorder. By varying the circulating fluid volume, ventricular function can be determined for varying preload pressures with fixed afterload pressure. Pilot experiments on board the NASA KC-135 aircraft have demonstrated proof-of-concept and provided early support for the proposed hypothesis. A review of the pilot experiments and developmental progress on the GAS version of this experiment will be presented.
Pantalos, George M.↗
Spectral analysis of resting cardiovascular variables and responses to oscillatory LBNP before and after 6 degree head dowm bedrest
A major focus of our research program is to develop noninvasive procedures for determining changes in cardiovascular function associated with the null gravity environment. We define changes in cardiovascular function to be (1) the result of the regulatory system operating at values different from 'normal' but with an overall control system basically unchanged by the null gravity exposure, or (2) the result of operating with a control system that has significantly different regulatory characteristics after an exposure. To this end, we have used a model of weightlessness that consisted of exposing humans to 2 hrs. in the launch position, followed by 20 hrs. of 6 deg head down bedrest. Our principal objective was to use this model to measure cardiovascular responses to the 6 deg head down bedrest protocol and to develop the most sensitive 'systems identification' procedure for indicating change. A second objective, related to future experiments, is to use the procedure in combination with experiments designed to determine the degree to which a regulatory pathway has been altered and to determine the mechanisms responsible for the changes.
Knapp, Charles F.↗
Instrumentation for Non-Invasive Assessment of Cardiovascular Regulation
It is critically important to be able to assess alterations in cardiovascular regulation during and after space flight. We propose to develop an instrument for the non-invasive assessment of such alterations that can be used on the ground and potentially during space flight. This instrumentation would be used by the Cardiovascular Alterations Team at multiple sites for the study of the effects of space flight on the cardiovascular system and the evaluation of countermeasures. In particular, the Cardiovascular Alterations Team will use this instrumentation in conjunction with ground-based human bed-rest studies and during application of acute stresses e.g., tilt, lower body negative pressure, and exercise. In future studies, the Cardiovascular Alterations Team anticipates using this instrumentation to study astronauts before and after space flight and ultimately, during space flight. The instrumentation may also be used by the Bone Demineralization/Calcium Metabolism Team, the Neurovestibular Team and the Human Performance Factors, Sleep and Chronobiology Team to measure changes in autonomic nervous function. The instrumentation will be based on a powerful new technology - cardiovascular system identification (CSI) - which has been developed in our laboratory. CSI provides a non-invasive approach for the study of alterations in cardiovascular regulation. This approach involves the analysis of second-to-second fluctuations in physiologic signals such as heart rate and non-invasively measured arterial blood pressure in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of multiple physiologic mechanisms, CSI provides a closed-loop model of the cardiovascular regulatory state in an individual subject.
Cohen, Richard J.↗
Influence of Population Variation of Physiological Parameters in Computational Models of Space Physiology
The earliest manifestations of Visual Impairment and Intracranial Pressure (VIIP) syndrome become evident after months of spaceflight and include a variety of ophthalmic changes, including posterior globe flattening and distension of the optic nerve sheath. Prevailing evidence links the occurrence of VIIP to the cephalic fluid shift induced by microgravity and the subsequent pressure changes around the optic nerve and eye. Deducing the etiology of VIIP is challenging due to the wide range of physiological parameters that may be influenced by spaceflight and are required to address a realistic spectrum of physiological responses. Here, we report on the application of an efficient approach to interrogating physiological parameter space through computational modeling. Specifically, we assess the influence of uncertainty in input parameters for two models of VIIP syndrome: a lumped-parameter model (LPM) of the cardiovascular and central nervous systems, and a finite-element model (FEM) of the posterior eye, optic nerve head (ONH) and optic nerve sheath. Methods: To investigate the parameter space in each model, we employed Latin hypercube sampling partial rank correlation coefficient (LHSPRCC) strategies. LHS techniques outperform Monte Carlo approaches by enforcing efficient sampling across the entire range of all parameters. The PRCC method estimates the sensitivity of model outputs to these parameters while adjusting for the linear effects of all other inputs. The LPM analysis addressed uncertainties in 42 physiological parameters, such as initial compartmental volume and nominal compartment percentage of total cardiac output in the supine state, while the FEM evaluated the effects on biomechanical strain from uncertainties in 23 material and pressure parameters for the ocular anatomy. Results and Conclusion: The LPM analysis identified several key factors including high sensitivity to the initial fluid distribution. The FEM study found that intraocular pressure and intracranial pressure had dominant impact on the peak strains in the ONH and retro-laminar optic nerve, respectively; optic nerve and lamina cribrosa stiffness were also important. This investigation illustrates the ability of LHSPRCC to identify the most influential physiological parameters, which must therefore be well-characterized to produce the most accurate numerical results.
biomechanics↗
An Integrated Biomechanical Model for Microgravity-Induced Visual Impairment
When gravitational unloading occurs upon entry to space, astronauts experience a major shift in the distribution of their bodily fluids, with a net headward movement. Measurements have shown that intraocular pressure spikes, and there is a strong suspicion that intracranial pressure also rises. Some astronauts in both short- and long-duration spaceflight develop visual acuity changes, which may or may not reverse upon return to earth gravity. To date, of the 36 U.S. astronauts who have participated in long-duration space missions on the International Space Station, 15 crew members have developed minor to severe visual decrements and anatomical changes. These ophthalmic changes include hyperopic shift, optic nerve distension, optic disc edema, globe flattening, choroidal folds, and elevated cerebrospinal fluid pressure. In order to understand the physical mechanisms behind these phenomena, NASA is developing an integrated model that appropriately captures whole-body fluids transport through lumped-parameter models for the cerebrospinal and cardiovascular systems. This data feeds into a finite element model for the ocular globe and retrobulbar subarachnoid space through time-dependent boundary conditions. Although tissue models and finite element representations of the corneo-scleral shell, retina, choroid and optic nerve head have been integrated to study pathological conditions such as glaucoma, the retrobulbar subarachnoid space behind the eye has received much less attention. This presentation will describe the development and scientific foundation of our holistic model.
Nelson, Emily S.↗
DigitalHuman (DH): An Integrative Mathematical Model ofHuman Physiology
Mathematical models and simulation are important tools in discovering the key causal relationships governing physiological processes and improving medical intervention when physiological complexity is a central issue. We have developed a model of integrative human physiology called DigitalHuman (DH) consisting of -5000 variables modeling human physiology describing cardiovascular, renal, respiratory, endocrine, neural and metabolic physiology. Users can view time-dependent solutions and interactively introduce perturbations by altering numerical parameters to investigate new hypotheses. The variables, parameters and quantitative relationships as well as all other model details are described in XML text files. All aspects of the model, including the mathematical equations describing the physiological processes are written in XML open source, text-readable files. Model structure is based upon empirical data of physiological responses documented within the peer-reviewed literature. The model can be used to understand proposed physiological mechanisms and physiological interactions that may not be otherwise intUitively evident. Some of the current uses of this model include the analyses of renal control of blood pressure, the central role of the liver in creating and maintaining insulin resistance, and the mechanisms causing orthostatic hypotension in astronauts. Additionally the open source aspect of the modeling environment allows any investigator to add detailed descriptions of human physiology to test new concepts. The model accurately predicts both qualitative and more importantly quantitative changes in clinically and experimentally observed responses. DigitalHuman provides scientists a modeling environment to understand the complex interactions of integrative physiology. This research was supported by.NIH HL 51971, NSF EPSCoR, and NASA
Hester, Robert L.↗
Influences of prostanoids and nitric oxide on post-suspension hypotension in female Sprague-Dawley rats
Impairment in cardiovascular functions sometimes manifested in astronauts during standing postflight, may be related to the diminished autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, using the 30 degrees head-down tilt (HDT) model, we compared the cardiovascular and biochemical effects of 7 days of suspension and a subsequent 6-h post-suspension period between suspended and non-suspended conscious female Sprague-Dawley rats. Mean arterial pressure (MAP) and heart rate were measured prior to suspension (basal), daily thereafter, and every 2h post-suspension. Following 7 days of suspension, MAP was not different from their basal values, however, upon release from suspension, MAP was significantly reduced compared to the non-suspended rats. Nitric oxide levels were elevated while thromboxane A(2) levels declined significantly in both plasma and tissue samples following post-suspension. The levels of prostacyclin following post-suspension remained unaltered in plasma and aortic rings but was significantly elevated in carotid arterial rings. Therefore, the post-suspension reduction in mean arterial pressure is due mostly to overproduction of nitric oxide and to a lesser extent prostacyclin.
Non-NASA Center↗
Flow and pressure regulation in the cardiovascular system
Principles and descriptive fragments which may contribute to a model of the regulating chains in the cardiovascular system are presented. Attention is given to the strain sensitivity of blood vessels, the law of the autonomy of the heart beat oscillator, the law of the encapsulation of body fluids, the law of the conservation of protein, the law of minimum 'arterial' pressure, the design of the 'mammalian' kidney, questions of homeokinetic organization, and the development of self-regulatory chains. Details concerning the development program for the heart muscle are considered along with the speed of response of the breathing rate and the significance of the pulmonary vascular pressure-flow characteristics.
Iberall, A.↗
The effects of exercise on blood flow with reference to the human cardiovascular system: a finite element study
This paper reports on a theoretical investigation into the effects of vasomotion on blood through the human cardiovascular system. The finite element method has been used to analyse the model. Vasoconstriction and vasodilation may be effected either through the action of the central nervous system or autoregulation. One of the conditions responsible for vasomotion is exercise. The proposed model has been solved and quantitative results of flows and pressures due to changing the conductances of specific networks of arterioles, capillaries and venules comprising the arms, legs, stomach and their combinations have been obtained.
NASA Discipline Cardiopulmonary↗
User's instructions for the whole-body algorithms
The design of an algorithm that provides for the simulation of long and short term biological stresses is reported. The physiological responses of models representing circulatory, respiratory, cardiovascular, and thermoregulatory systems during space flight simulation are described.
Grounds, D. J.↗
Delineating the Impact of Weightlessness on Human Physiology Using Computational Models
Microgravity environment has profound effects on several important human physiological systems. The impact of weightlessness is usually indirect as mediated by changes in the biological fluid flow and transport and alterations in the deformation and stress fields of the compliant tissues. In this context, Fluid-Structural and Fluid-Solid Interaction models provide a valuable tool in delineating the physical origins of the physiological changes so that systematic countermeasures can be devised to reduce their adverse effects. In this presentation, impact of gravity on three human physiological systems will be considered. The first case involves prediction of cardiac shape change and altered stress distributions in weightlessness. The second, presents a fluid-structural-interaction (FSI) analysis and assessment of the vestibular system and explores the reasons behind the unexpected microgravity caloric stimulation test results performed aboard the Skylab. The last case investigates renal stone development in microgravity and the possible impact of re-entry into partial gravity on the development and transport of nucleating, growing, and agglomerating renal calculi in the nephron. Finally, the need for model validation and verification and application of the FSI models to assess the effects of Artificial Gravity (AG) are also briefly discussed.
Computational Models↗
Numerical Modeling of Ocular Dysfunction in Space
Upon introduction to microgravity, the near-loss of hydrostatic pressure causes a marked cephalic (headward) shift of fluid in an astronaut's body. The fluid shift, along with other factors of spaceflight, induces a cascade of interdependent physiological responses which occur at varying time scales. Long-duration missions carry an increased risk for the development of the Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath, kinking of the optic nerve and potentially permanent degradation of visual function. In the cases of VIIP found to date, the initial onset of symptoms occurred after several weeks to several months of spaceflight, by which time the gross bodily fluid distribution is well established. We are developing a suite of numerical models to simulate the effects of fluid shift on the cardiovascular, central nervous and ocular systems. These models calculate the modified mean volumes, flow rates and pressures that are characteristic of the altered quasi-homeostatic state in microgravity, including intracranial and intraocular pressures. The results of the lumped models provide initial and boundary data to a 3D finite element biomechanics simulation of the globe, optic nerve head and retrobulbar subarachnoid space. The integrated set of models will be used to investigate the evolution of the biomechanical stress state in the ocular tissues due to long-term exposure to microgravity.
intraocular pressure↗
Minipigs as a Model to Study Separate and Combined Effects of Space Radiation and Altered Gravity on Cardiovascular disease, Spaceflight-Associated Neuro-Ocular Syndrome (SANS), and Central Nervous System (CNS) effects
Minipigs are a well-characterized animal model used to study thecardiovascular system, metabolism, bone, gastrointestinal tract,pancreas, liver, kidney, lung, immune system, central nervous system(white matter) etc. Due to their anatomical, physiological, andbiochemical similarities to humans, minipigs are considered atranslational model in biomedical research and development. Also, their large size and cognitive abilities allow collection of supplementary information regarding the central nervous system(BMed) and Spaceflight-Associated Neuro-Ocular Syndrome (SANS) risk.
Janapriya Saha↗
Evaluation of biological models using Spacelab
Biological models of hypogravity effects are described, including the cardiovascular-fluid shift, musculoskeletal, embryological and space sickness models. These models predict such effects as loss of extracellular fluid and electrolytes, decrease in red blood cell mass, and the loss of muscle and bone mass in weight-bearing portions of the body. Experimentation in Spacelab by the use of implanted electromagnetic flow probes, by fertilizing frog eggs in hypogravity and fixing the eggs at various stages of early development and by assessing the role of the vestibulocular reflex arc in space sickness is suggested. It is concluded that the use of small animals eliminates the uncertainties caused by corrective or preventive measures employed with human subjects.
Tollinger, D.↗