Long-term microgravity exposure increases ECG repolarization instability manifested by low-frequency oscillations of T-Wave vector

Ventricular arrhythmias and sudden cardiac death during long-term space missions are a major concern for space agencies. Long-duration spaceflight and its ground-based analog head-down bed rest (HDBR) have been reported to markedly alter autonomic and cardiac functioning, particularly affecting ventricular repolarization of the electrocardiogram (ECG). In this study, novel methods are developed, departing from previously published methodologies, to quantify the index of Periodic Repolarization Dynamics (PRD), an arrhythmic risk marker that characterizes sympathetically-mediated low-frequency oscillations in the T-wave vector. PRD is evaluated in ECGs from 42 volunteers at rest and during an orthostatic tilt table test recorded before and after 60-day –6° HDBR. Our results indicate that tilt test, on top of enhancing sympathetic regulation of heart rate, notably increases PRD, both before and after HDBR, thus supporting previous evidence on PRD being an indicator of sympathetic modulation of ventricular repolarization. Importantly, long-term microgravity exposure is shown to lead to significant increases in PRD, both when evaluated at rest and, even more notably, in response to tilt test. The extent of microgravity-induced changes in PRD has been associated with arrhythmic risk in prior studies. An exercise-based, but not a nutrition-based, countermeasure is able to partially reverse microgravity-induced effects on PRD. In conclusion, long-term exposure to microgravity conditions leads to elevated low-frequency oscillations of ventricular repolarization, which are potentiated following sympathetic stimulation and are related to increased risk for repolarization instabilities and arrhythmias. Tested countermeasures are only partially effective in counteracting microgravity effects

Heart-Lung Interactions in Aerospace Medicine

Few of the heart-lung interactions that are discussed have been studied in any detail in the aerospace environment, but is seems that many such interactions must occur in the setting of altered accelerative loadings and pressure breathing. That few investigations are in progress suggests that clinical and academic laboratory investigators and aerospace organizations are further apart than during the pioneering work on pressure breathing and acceleration tolerance in the 1940s. The purpose is to reintroduce some of the perennial problems of aviation physiology as well as some newer aerospace concerns that may be of interest. Many possible heart-lung interactions are pondered, by necessity often drawing on data from within the aviation field, collected before the modern understanding of these interactions developed, or on recent laboratory data that may not be strictly applicable. In the field of zero-gravity effects, speculation inevitably outruns the sparse available data

Publications of the Space Physiology and Countermeasures Program, Cardiopulmonary Discipline: 1980-1990

A 10-year cumulative bibliography of publications resulting from research supported by the Cardiopulmonary Discipline of the Space Physiology and Countermeasures Program of NASA's Life Sciences Division is provided. Primary subjects included in this bibliography are Fluid Shifts, Cardiovascular Fitness, Cardiovascular Physiology, and Pulmonary Physiology. General physiology references are also included. Principal investigators whose research tasks resulted in publication are identified. Publications are identified by a record number corresponding with their entry in the Life Sciences Bibliographic Database, maintained at the George Washington University

Effects of Spaceflight on Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Structure and Function.

With extended stays aboard the International Space Station (ISS) becoming commonplace, there is a need to better understand the effects of microgravity on cardiac function. We utilized human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study the effects of microgravity on cell-level cardiac function and gene expression. The hiPSC-CMs were cultured aboard the ISS for 5.5 weeks and their gene expression, structure, and functions were compared with ground control hiPSC-CMs. Exposure to microgravity on the ISS caused alterations in hiPSC-CM calcium handling. RNA-sequencing analysis demonstrated that 2,635 genes were differentially expressed among flight, post-flight, and ground control samples, including genes involved in mitochondrial metabolism. This study represents the first use of hiPSC technology to model the effects of spaceflight on human cardiomyocyte structure and function

Cardiopulmonary discipline science plan

Life sciences research in the cardiopulmonary discipline must identify possible consequences of space flight on the cardiopulmonary system, understand the mechanisms of these effects, and develop effective and operationally practical countermeasures to protect crewmembers inflight and upon return to a gravitational environment. The long-range goal of the NASA Cardiopulmonary Discipline Research Program is to foster research to better understand the acute and long-term cardiovascular and pulmonary adaptation to space and to develop physiological countermeasures to ensure crew health in space and on return to Earth. The purpose of this Discipline Plan is to provide a conceptual strategy for NASA's Life Sciences Division research and development activities in the comprehensive area of cardiopulmonary sciences. It covers the significant research areas critical to NASA's programmatic requirements for the Extended-Duration Orbiter, Space Station Freedom, and exploration mission science activities. These science activities include ground-based and flight; basic, applied, and operational; and animal and human research and development. This document summarizes the current status of the program, outlines available knowledge, establishes goals and objectives, identifies science priorities, and defines critical questions in the subdiscipline areas of both cardiovascular and pulmonary function. It contains a general plan that will be used by both NASA Headquarters Program Offices and the field centers to review and plan basic, applied, and operational (intramural and extramural) research and development activities in this area

Cardiac and Vascular Responses to Thigh Cuffs and Respiratory Maneuvers on Crewmembers of the International Space Station

The transition to microgravity eliminates the hydrostatic gradients in the vascular system. The resulting fluid redistribution commonly manifests as facial edema, engorgement of the external neck veins, and a decrease in leg diameter. This experiment examined the responses to modified Valsalva and Mueller maneuvers measured by cardiac and vascular ultrasound (ECHO) in a baseline steady state and during preload reduction introduced with thigh occlusion cuffs used as a counter-measure device (Braslet cuffs) measured by cardiac and vascular ultrasound examinations. Methods: Nine International Space Station crewmember subjects (Expeditions 16 - 20) were examined in 15 experiment sessions 101 +/- 46.days after launch (mean +/- SD; 33 - 185). Twenty Seven cardiac and vascular parameters were obtained with/without respiratory maneuvers before and after tightening of the Braslet cuffs. Results: Non-physicians performed diagnostic-quality cardiac and vascular ultrasound examinations using remote guidance. Three of 27 combinations of maneuvers and Braslet or Braslet alone were identified as being significant changed when compared to baseline. Eleven of 81 differences between combinations of Mueller, Valsalva or baseline were significant and related to cardiac preload reduction or increase in lower extremity venous volume. Conclusions: Acute application of Braslet occlusion cuffs causes lower extremity fluid sequestration and exerts commensurate measurable effects on cardiac performance in microgravity. Ultrasound techniques to measure the hemodynamic effects of thigh cuffs in combination with respiratory maneuvers may serve as an invaluable tool in determining the volume status of the cardiac patient at the 'microgravity bedside'

Weightlessness and Cardiac Rhythm Disorders: Current Knowledge from Space Flight and Bed-Rest Studies

Isolatedepisodesofheartrhythmdisordershavebeenreportedduring40yearsofspaceflight,triggeringresearchtoevaluatetheriskofdevelopinglife-threateningarrhythmiasinducedbyprolongedexposuretoweightlessness.Infact,theseeventscouldcompromiseastronautperformanceduringexploratorymissions,aswellasposeatrisktheastronauthealth,duetolimitedoptionsofcareonboardtheInternationalSpaceStation.Startingfromoriginalobservations,thisminireviewwillexplorethelatestresearchinthisfield,consideringresultsobtainedbothduringspaceflightandonEarth,thelatterbysimulatinglong-termexposuretomicrogravitybyhead-downbedrestmaneuverinordertoelicitcardiovasculardeconditioningonnormalvolunteers

Cardiovascular deconditioning during long-term spaceflight through multiscale modeling

Human spaceflight has been fascinating man for centuries, representing the intangible need to explore the unknown, challenge new frontiers, advance technology and push scientific boundaries further. A key area of importance is cardiovascular deconditioning, that is, the collection of hemodynamic changes - from blood volume shift and reduction to altered cardiac function - induced by sustained presence in microgravity. A thorough grasp of the 0G adjustment point per se is important from a physiological viewpoint and fundamental for astronauts' safety and physical capability on long spaceflights. However, hemodynamic details of cardiovascular deconditioning are incomplete, inconsistent and poorly measured to date; thus a computational approach can be quite valuable. We present a validated 1D-0D multiscale model to study the cardiovascular response to long-term 0G spaceflight in comparison to the 1G supine reference condition. Cardiac work, oxygen consumption and contractility indexes, as well as central mean and pulse pressures were reduced, augmenting the cardiac deconditioning scenario. Exercise tolerance of a spaceflight traveler was found to be comparable to an untrained person with a sedentary lifestyle. At the capillary-venous level significant waveform alterations were observed which can modify the regular perfusion and average nutrient supply at the cellular level. The present study suggests special attention should be paid to future long spaceflights which demand prompt physical capacity at the time of restoration of partial gravity (e.g., Moon/Mars landing). Since spaceflight deconditioning has features similar to accelerated aging understanding deconditioning mechanisms in microgravity are also relevant to the understanding of aging physiology on Earth.Comment: 14 pages, 5 tables, 5 figure

Mechanisms of Orthostatic Intolerance During Real and Simulated Microgravity

Session MP1 includes short reports on: (1) Orthostatic Tests after 42 Days of Simulated Weightlessness; (2) Effects of 12 Days Exposure to Simulated Microgravity on Central Circulatory Hemodynamics in the Rhesus Monkey; (3) Increased Sensitivity and Resetting of Baroflex Control of Exercise Heart Rate After Prolonged Bed-Rest; (4) Complex Cardiovascular Dynamics and Deconditioning During Head-down Bed Rest; (5) The Cardiovascular Effects of 6 Hours of Head-down Tilt Upon Athletes and Non-athletes; (6) Individual Susceptibility to Post-spaceflight Orthostatic Intolerance: Contributions of Gender-related and Microgravity-related Factors; (7) Cassiopee Mission 1996: Comparison of Cardiovascular Alteration after Short and Long-term Spaceflights; (8) Cerebral and Femoral Flow Response to LBNP during 6 Month MIR Spaceflights (93-95); and (9) Cerebrovascular Changes due to Spaceflight and Postflight Presyncope