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All sourcesNASA NTRSDOE OSTI
NASA NTRS2006

User Interactive Software for Analysis of Human Physiological Data

Ambulatory physiological monitoring has been used to study human health and performance in space and in a variety of Earth-based environments (e.g., military aircraft, armored vehicles, small groups in isolation, and patients). Large, multi-channel data files are typically recorded in these environments, and these files often require the removal of contaminated data prior to processing and analyses. Physiological data processing can now be performed with user-friendly, interactive software developed by the Ames Psychophysiology Research Laboratory. This software, which runs on a Windows platform, contains various signal-processing routines for both time- and frequency- domain data analyses (e.g., peak detection, differentiation and integration, digital filtering, adaptive thresholds, Fast Fourier Transform power spectrum, auto-correlation, etc.). Data acquired with any ambulatory monitoring system that provides text or binary file format are easily imported to the processing software. The application provides a graphical user interface where one can manually select and correct data artifacts utilizing linear and zero interpolation and adding trigger points for missed peaks. Block and moving average routines are also provided for data reduction. Processed data in numeric and graphic format can be exported to Excel. This software, PostProc (for post-processing) requires the Dadisp engineering spreadsheet (DSP Development Corp), or equivalent, for implementation. Specific processing routines were written for electrocardiography, electroencephalography, electromyography, blood pressure, skin conductance level, impedance cardiography (cardiac output, stroke volume, thoracic fluid volume), temperature, and respiration

Cowings, Patricia S.↗
NASA NTRS2011

Use of Minute-by-Minute Cardiovascular Measurements During Tilt Tests to Strengthen Inference on the Effect of Long-Duration Space Flight on Orthostatic Hypotension

Typical methodology for evaluating the effects of spaceflight on orthostatic hypotension (OH) has been survival analysis of tolerance times from 80 head-up tilt tests. However when scheduled test durations are short, there may not be enough failures to allow survival analysis to adequately estimate and compare the effects of flight phase (e.g. pre-flight, number of days post-flight), flight duration, and their interaction, as well as interactions with effects of interventions or countermeasures. The problem is exacerbated in the presence of a repeated measures design, in which subjects participate in tilt tests during various flight phases. Here we show how it is possible to dramatically improve the efficiency of statistical inference in this setting by making use of the additional information contained in minute-by-minute observations of cardiovascular parameters thought to be reflective of progression towards presyncope during tilt testing. Methods: We retrospectively examined operational tilt test (OTT; 10 -min 80 head-up tilt) data from 20 International Space Station (ISS) and 66 Shuttle astronauts 10 d before launch (L-10), on landing day (R+0) and during recovery (R+1, R+3, R+6-10) depending on the level of participation. Data from 5 ISS astronauts tested on R+0 or R+1 who used non-standard countermeasures were excluded. In addition to OTT survival time, 8 cardiovascular parameters (CP: heart rate, systolic, diastolic, and mean arterial blood pressure, pulse pressure, stroke volume, cardiac output, and total peripheral resistance) that might be predictive of progression towards presyncope were measured every minute of each OTT. Statistical analysis was predicated on a two ]stage model of causation. In the first stage, flight duration and time from landing affect the astronauts' degree of OH, which is manifested in the time trends and variation of the above CPs during OTTs. In the second stage, the behavior of these parameters directly affects OTT survival time. Actual analysis proceeded in the opposite direction. First we identified those CPs or linear combinations that best predicted OTT survival regardless of what spaceflight conditions led to OTT completion or presyncope. From these, we calculated a summary statistic (one per OTT) that best predicted survival. We then used mixed ]model regression analysis to relate changes in the summary statistic to flight phase and duration. Inference on the effects of phase, duration, and their interaction on OH follows directly from this second analysis. Results: A linear combination (W) of diastolic blood pressure (DBP) and stroke volume (SV) was found to be the best predictor of OTT survival using the complete data set of minute-by-minute observations of CPs for each OTT. Furthermore, the log-transformed standard deviation of W (Z = log SW) was found to be a strong predictor of survival in the reduced data set consisting of one observation per OTT. In other words, this measure of variability of W during an OTT was the best indicator of whether or not the subject could complete the 10-min test, with higher variability (i.e. higher values of Z) being associated with greater probability of failure. In the mixed-model regression analysis where Z was now treated as a outcome with flight phase and duration groups (ISS and STS) as predictors, we found that there was a significantly more variability in W (higher values of Z) for both groups at R+0, but with no evidence of an interaction until R+3, when the ISS group still had inflated variability, but not the STS group. Conclusions: Variability of the cardiovascular index W recovers more slowly after long-compared to short-duration spaceflight. Since high variability of W has also been shown to be predictive of OTT failure, a primary manifestation of OH, a logical conclusion is that recovery from OH also is slower after long-duration compared to short-duration spaceflights.

Feiveson, Alan H.↗
NASA NTRS2011

A Data Mining Project to Identify Cardiovascular Related Factors That May Contribute to Changes in Visual Acuity Within the US Astronaut Corps

Many of the cardiovascular-related adaptations that occur in the microgravity environment are due, in part, to a well-characterized cephalad-fluid shift that is evidenced by facial edema and decreased lower limb circumference. It is believed that most of these alterations occur as a compensatory response necessary to maintain a "normal" blood pressure and cardiac output while in space. However, data from both flight and analog research suggest that in some instances these microgravity-induced alterations may contribute to cardiovascular-related pathologies. Most concerning is the potential relation between the vision disturbances experienced by some long duration crewmembers and changes in cerebral blood flow and intra-ocular pressure. The purpose of this project was to identify cardiovascular measures that may potentially distinguish individuals at risk for visual disturbances after long duration space flight. Toward this goal, we constructed a dataset from Medical Operation tilt/stand test evaluations pre- (days L-15-L-5) and immediate post-flight (day R+0) on 20 (3 females, 17 males). We restricted our evaluation to only crewmembers who participated in both shuttle and space station missions. Data analysis was performed using both descriptive and analytical methods (Stata 11.2, College Station, TX) and are presented as means +/- 95% CI. Crewmembers averaged 5207 (3447 - 8934) flight hours across both long (MIR-23 through Expedition16) and short (STS-27 through STS-101) duration missions between 1988 and 2008. The mean age of the crew at the time of their most recent shuttle flight was 41 (34-44) compared to 47 (40-54) years during their time on station. In order to focus our analysis (we did not have codes to separate out subjects by symptomotology) , we performed a visual inspection of each cardiovascular measures captured during testing and plotted them against stand time, pre- to post-flight, and between mission duration. It was found that pulse pressure most clearly differentiated the two mission types. Statistical analysis confirmed that pulse pressure was significantly higher before [45.6; (42.1 to 49.1)] and after [50.7; (46.9 to 54.6)] time on station compared with their most recent shuttle flight [31.6 (27.8 to 35.4), and 32.2 (28.3 to 36.0) respectively] even after correcting differences in age and cumulative number of mission hours. Without knowing the identity of which long duration crewmembers demonstrated visual changes, we were limited to examining whether certain crew regulate components of pulse pressure, systolic and diastolic blood pressure, differently due to microgravity exposure. To that end, we stratified crew into tertiles based on either their pre-flight measure of systolic or diastolic blood pressure. Those crew in the highest tertile for both systolic (lower tertile (n=8; 103-111), middle tertile (n=7; 113-121), and upper tertile (n=5; 125-136) and diastolic blood pressure (lower tertile (n=8; 58-64), middle tertile (n=7; 67-73), and upper tertile (n=5; 75-81) demonstrated less variability in pulse pressure between R+0 and L-10 (Figure 2). Interestingly, those crewmembers with the highest resting systolic blood pressure demonstrated either no change or in some instances an increase in total peripheral resistance, where those in the lower tertiles had lower values of total peripheral resistance compared to pre-flight levels. In this study, it was found that crewmembers in the highest tertile for both systolic and diastolic blood pressure demonstrated less variability in pulse pressure and that the decrease in variability was due in part to lower levels of compliance as indicated by similar or higher levels of total peripheral resistance after compared with before flight levels. Whether there is a relation between blood pressure regulation and total peripheral resistance in crew presenting with negative changes in visual acuity remains unknown.

Westby, Christian M.↗
NASA NTRS2013

Association Between Cardiovascular and Intraocular Pressure Changes in a 14-Day 6 deg Head Down Tilt (HDT) Bed Rest Study: Possible Implications in Retinal Anatomy

Visual symptoms and intracranial pressure increase reported in astronauts returning from long duration missions in low Earth-orbit are thought to be related to fluid shifts within the body due to microgravity exposure. Because of this possible relation to fluid shifts, studies conducted in head-down tilt (HDT) bed rest are being monitored for potential changes in ocular health. These measures will also serve to determine whether HDT is a suitable ground-based analog to model subclinical cardiovascular and ocular changes that could shed light on the etiology of the VIIP syndrome observed in spaceflight. Sixteen healthy normotensive (12M, 4F, age range 29-54 years), non-smoker and normal weight subjects, volunteered to participate in a 14 day 6 deg head HDT study conducted at the NASA Flight Analogs Research Unit (FARU). This facility provides standard bed rest conditions (diet, wake/sleep time, time allowed in sunlight) during the time that the subjects stay at the FARU. Cardiovascular parameters were obtained in supine posture at BR-5, BR+0, and BR+3 and ocular monitoring was performed weekly. Intraocular pressure (IOP) increased from pre-bed rest BR-3) to the third day into bed rest (BR+3). Values reached a plateau towards the end of the bed rest phase (BR10) and decreased within the first three days of recovery (BR+2) returning to levels comparable to baseline at BR-3. As expected, most cardiovascular parameters were affected by 14 days of HDT bed rest. Plasma volume decreased as a result of bed rest but recovered to baseline levels by BR+3. Indications of cardiovascular deconditioning included increase in both systolic and diastolic blood pressure and heart rate, and a decrease in stroke volume and cardiac output between BR-5 and BR+3. Due to the experimental design of this study, we were not able to test the hypothesis that fluid shifts might be involved in the IOP increase during the bed rest phase, since cardiovascular measures were not available for those time points. There was no correlation between the largest change in IOP (BR-3 versus BR3) and cardiovascular measure changes between baseline (BR-5) and post bed rest (BR+2). While no clinically relevant visual changes were observed during the study, measurement of various retinal parameters was performed with optical coherence tomography (OCT). A decrease in central subfield retinal thickness was observed between BR+2 and baseline at BR-10, but no association was observed with IOP changes. This work investigates the time course of changes in IOP during 14-day HDT bed rest in an attempt to characterize HDT bed rest as a model of the VIIP syndrome and delve into its etiology.

Cromwell, Ronita↗
NASA NTRS2014

Convective and Diffusive O2 Transport Components of Peak Oxygen Uptake Following Long-duration Spaceflight

Spaceflight reduces aerobic capacity and may be linked with maladaptations in the O2 transport pathway. The aim was to 1) evaluate the cardiorespiratory adaptations following 6 months aboard the International Space Station and 2) model the contributions of convective (Q (raised dot) O2) and peripheral diffusive (DO2) components of O2 transport to changes in peak O2 uptake (V (raised dot) O2PEAK). To date, 1 male astronaut (XX yrs) completed an incremental exercise test to measure V (raised dot) O2PEAK prior to and 2 days post-flight. Cardiac output (Q (raised dot) ) was measured at three submaximal work rates via carbon dioxide rebreathing. The Q (raised dot) :V (raised dot) O2 relationship was extrapolated to V (raised dot) O2PEAK to determine Q (raised dot) PEAK. Hemoglobin concentration was measured at rest via a venous blood sample. These measurements were used to model the changes in Q (raised dot) O2 and DO2 using Fick's principle of mass conservation and Law of Diffusion as established by Wagner and colleagues (Annu. Rev. Physiol 58: 21-50, 1996 and J. Appl. Physiol. 73: 1067-1076, 1992). V (raised dot) O2PEAK decreased postflight from 3.72 to 3.45 l min-1, but Q (raised dot) PEAK increased from 24.5 to 27.7 l min-1. The decrease in V (raised dot) O2PEAK post-flight was associated with a 21.2% decrease in DO2, an 18.6% decrease in O2 extraction, but a 3.4% increase in Q (raised dot) O2. These preliminary data suggest that long-duration spaceflight reduces peripheral diffusing capacity and that it largely contributes to the post-flight decrease in aerobic capacity.

Ade, Carl J.↗
NASA NTRS2014

Peak Oxygen Uptake during and after Long-duration Space Flight

Aerobic capacity (VO2peak) previously has not been measured during or after long-duration spaceflight. PURPOSE: To measure VO2peak and submaximal exercise responses during and after International Space Station (ISS) missions. METHODS: Astronauts (9 M, 5 F: 49 +/- 5 yr, 175 +/- 7 cm, 77.2 +/- 15.1 kg, 40.6 +/- 6.4 mL/kg/min [mean +/-SD]) performed graded peak cycle tests ~90 days before spaceflight, 15 d (FD15) after launch and every ~30 d thereafter during flight, and 1 (R+1), 10 (R+10), and 30 d (R+30) after landing. Oxygen consumption (VO2) and heart rate (HR) were measured from rest to peak exercise, while cardiac output (Q), stroke volume (SV), and arterial-venous oxygen difference (a-vO2diff) were measured only during rest and submaximal exercise. Data were analyzed using mixed-model linear regression. Body mass contributed significantly to statistical models, and thus results are reported as modeled estimates for an average subject. RESULTS: Early inflight (FD15) VO2peak was 17% lower (95% CI = - 22%, -13%) than preflight. VO2peak increased during spaceflight (0.001 L/min/d, P = 0.02) but did not return to preflight levels. On R+1 VO2peak was 15% (95% CI = -19%, -10%) lower than preflight but recovered to within 2% of preflight by R+30 (95% CI = -6%, +3%). Peak HR was not significantly different from preflight at any time. Inflight submaximal VO2 and a-vO2diff were generally lower than preflight, but the Q vs. VO2 slope was unchanged. In contrast, the SV vs. VO2 slope was lower (P < 0.001), primarily due to elevated SV at rest, and the HR vs. VO2 slope was greater (P < 0.001), largely due to elevated HR during more intense exercise. On R+1 although the relationships between VO2 and Q, SV, and HR were not statistically different than preflight, resting and submaximal exercise SV was lower (P < 0.001), resting and submaximal exercise HR was higher (P < 0.002), and a-vO2diff was unchanged. HR and SV returned to preflight levels by R+30. CONCLUSION: In the average astronaut VO2peak was reduced during spaceflight and immediately after landing but factors contributing to lower VO2peak may be different during spaceflight and recovery. Maintaining Q while VO2 is reduced inflight may be suggestive of an elevated blood flow to vascular beds other than exercising muscles, but decreased SV after flight likely reduces Q at peak exertion.

Moore, Alan D., Jr.↗
NASA NTRS2001

Efficacy of Cardiopulmonary Resuscitation in the Microgravity Environment

End tidal carbon dioxide (EtCO 2) has been previously shown to be an effective non-invasive tool for estimating cardiac output during cardiopulmonary resuscitation (CPR). Animal models have shown that this diagnostic adjunct can be used as a predictor of survival when EtCO 2 values are maintained above 25% of prearrest values.

Johnston, Smith L.↗
NASA NTRS2018

Evaluation of the Danish Aerospace Corporation Portable Pulmonary Function System

A research project designed to investigate changes in maximal oxygen consumption (VO2max) during and following long duration flight on the International Space Station (ISS) has recently been completed. The device used to measure VO2 on board ISS, the Portable Pulmonary Function System (PPFS) manufactured by the Danish Aerospace Corporation (DAC), is based on previous-generation devices manufactured by DAC, but the PPFS has not been validated for analyzing metabolic gases or measuring cardiac output (Qc). The purpose of the present evaluation is to compare PPFS metabolic gas analysis measurements to measurements obtained using a clinically-validated system (ParvoMedics TrueOne(c) 2400 system; Parvo). In addition, Qc data collected with the PPFS were compared to Qc measurements from echocardiography. METHODS: Ten subjects completed three cycle exercise tests to maximal exertion. The first test was conducted to determine each subject's VO2max and set the work rates for the second and third (comparison) tests. The protocol for the two comparison tests consisted of three 5-minute stages designed to elicit 25%, 50%, and 75% VO2max (based upon results from the initial test), followed by 1-minute stages of increasing work rate (25 watt/minute) until the subject reached maximal effort. During one of the two comparison tests, metabolic gases and Qc were assessed with the PPFS; metabolic gases and Qc were assessed with the Parvo and by echocardiography, respectively, during the other test. The order of the comparison tests was counterbalanced. VO2max and maximal work rate during the comparison tests were compared using t tests. Mixed-effects regression modeling was used to analyze submaximal data. RESULTS: All of the data were within normal physiological ranges. The PPFS-measured values for VO2max were 6% lower than values obtained with the Parvo (PPFS: 3.11 +/- 0.75 L/min; Parvo: 3.32 +/- 0.87 L/min; mean +/- standard deviation; P = 0.02); this difference is probably due to flow restriction imposed by the PPFS Qc accessories. Submaximal VO2 values were slightly lower when measured with the PPFS, although differences were not physiologically relevant. The PPFS-measured values of submaximal carbon dioxide production (VCO2) were lower than the data obtained from Parvo, which could be attributed to lower fractions of expired carbon dioxide measured by the PPFS. The PPFS Qc values tended to be lower than echocardiography-derived values. CONCLUSIONS: The results of the present study indicate a need to further examine the PPFS and to better quantify its reproducibility; however, none of the findings of the current evaluation indicate that the PPFS needs to be replaced or modified.

Portable Pulmonary Function System (PPFS)↗
NASA NTRSDate not supplied

Citizen Science Approach for Searching and Curating Literature of the Effects of Spaceflight on Cardiovascular Outcomes in Rodents and Humans

The spaceflight environment causes significant changes to the structure and function of the cardiovascular system, including fluid redistribution, alterations in blood pressure, and changes in cardiac output. The goal of this project is to quantitatively summarize the data on the effects of actual or simulated microgravity and radiation exposure resulting from spaceflight on the cardiovascular system. As the first step, a group of investigators approached through a collaboration of the Ames Life Science Data Archive (ALSDA) Analysis Working Group developed a list of relevant cardiovascular search terms. Based on these, medical librarians generated and executed the search strategy in Medline, CINAHL, Embase and NASA repositories. In parallel, we recruited students and young professionals from various space industry-affiliated organizations, resulting in ~100 individuals joining. With this program we aimed to reach students and young people underrepresented in STEM, including first-generation, female, minorities, disadvantaged backgrounds, fostered individuals, etc. These individuals completed a virtual training course on the nature and methodologies of the project. Following this, the participants were structured into teams with more senior/experienced individuals designated as team leaders. Currently, the teams are screening approximately 15,000 studies using the systematic review tool, Covidence. Teams will be extracting and curating data for meta-analysis of the cardiovascular spaceflight literature, but also extracting, submitting, and curating appropriate datasets into the new ALSDA submission portal and repository. This effort will result in collaborative publications based upon the literature meta-analyses, and a number of publicly accessible datasets for reuse, modeling, machine learning, and knowledge graph-type approaches. This approach reduces the length of time to complete title/abstract screening time from 1-2 years needed for this volume of studies, to 3-4 months, while also providing a unique, open-access educational experience to space research and training in knowledge synthesis tools to interested individuals.

space biology↗
NASA NTRSDate not supplied

Mitigating Headward Fluid Shifts With Veno-Constrictive Thigh Cuffs During Spaceflight

Astronauts experience a chronic headward fluid shift in weightlessness as evidenced by increased cardiac output, decreased leg volume, a redistribution of venous fluid, and venous congestion in the upper body. Alterations in cerebrospinal fluid hydrodynamics and changes in cerebral venous pressure secondary to the headward fluid shift may contribute to ocular changes associated with spaceflight-associated neuro-ocular syndrome (SANS). Veno-constrictive thigh cuffs (VTC; Braslets) provided to Soyuz crewmembers alleviate symptoms of the headward fluid shift during the first week of spaceflight and have been documented to reduce internal jugular vein (IJV) distension during weightlessness. Application of VTCs designed collaboratively by NASA Johnson Space Center Cardiovascular and Vision Laboratory (CVL) and Clemson Textile Laboratory at Clemson University to improve fit and comfort was documented to mitigate changes in choroid thickness, intraocular pressure, and IJV area during posture-induced headward fluid shifts. VTC are demonstrated to reduce headward fluid shifts in both ground-based and spaceflight studies, and thus, may be a countermeasure against development of SANS. In addition, VTC are a simple mechanical countermeasure currently at a high technical readiness level (TRL) and are compact and lightweight, making them compatible with the spaceflight operations environment

Connor R. Ferguson↗
NASA NTRS2001

LabHEART: an interactive computer model of rabbit ventricular myocyte ion channels and Ca transport

An interactive computer program, LabHEART, was developed to simulate the action potential (AP), ionic currents, and Ca handling mechanisms in a rabbit ventricular myocyte. User-oriented, its design allows switching between voltage and current clamp and easy on-line manipulation of key parameters to change the original formulation. The model reproduces normal rabbit ventricular myocyte currents, Ca transients, and APs. We also changed parameters to simulate data from heart failure (HF) myocytes, including reduced transient outward (I(to)) and inward rectifying K currents (I(K1)), enhanced Na/Ca exchange expression, and reduced sarcoplasmic reticulum Ca-ATPase function, but unaltered Ca current density. These changes caused reduced Ca transient amplitude and increased AP duration (especially at lower frequency) as observed experimentally. The model shows that the increased Na/Ca exchange current (I(NaCa)) in HF lowers the intracellular [Ca] threshold for a triggered AP from 800 to 540 nM. Similarly, the decrease in I(K1) reduces the threshold to 600 nM. Changes in I(to) have no effect. Combining enhanced Na/Ca exchange with reduced I(K1) (as in HF) lowers the threshold to trigger an AP to 380 nM. These changes reproduce experimental results in HF, where the contributions of different factors are not readily distinguishable. We conclude that the triggered APs that contribute to nonreentrant ventricular tachycardia in HF are due approximately equally (and nearly additively) to alterations in I(NaCa) and I(K1). A free copy of this software can be obtained at http://www.meddean.luc.edu/lumen/DeptWebs/physio/bers.html.

NASA Discipline Cardiopulmonary↗
NASA NTRS2001

Cardiac atrophy after bed rest and spaceflight

Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity of cardiac muscle under different loading conditions.

Flight Experiment↗
NASA NTRS2000

Contractile reserve and intracellular calcium regulation in mouse myocytes from normal and hypertrophied failing hearts

Mouse myocyte contractility and the changes induced by pressure overload are not fully understood. We studied contractile reserve in isolated left ventricular myocytes from mice with ascending aortic stenosis (AS) during compensatory hypertrophy (4-week AS) and the later stage of early failure (7-week AS) and from control mice. Myocyte contraction and [Ca(2+)](i) transients with fluo-3 were measured simultaneously. At baseline (0.5 Hz, 1.5 mmol/L [Ca(2+)](o), 25 degrees C), the amplitude of myocyte shortening and peak-systolic [Ca(2+)](i) in 7-week AS were not different from those of controls, whereas contraction, relaxation, and the decline of [Ca(2+)](i) transients were slower. In response to the challenge of high [Ca(2+)](o), fractional cell shortening was severely depressed with reduced peak-systolic [Ca(2+)](i) in 7-week AS compared with controls. In response to rapid pacing stimulation, cell shortening and peak-systolic [Ca(2+)](i) increased in controls, but this response was depressed in 7-week AS. In contrast, the responses to both challenge with high [Ca(2+)](o) and rapid pacing in 4-week AS were similar to those of controls. Although protein levels of Na(+)-Ca(2+) exchanger were increased in both 4-week and 7-week AS, the ratio of SR Ca(2+)-ATPase to phospholamban protein levels was depressed in 7-week AS compared with controls but not in 4-week AS. This was associated with an impaired capacity to increase sarcoplasmic reticulum Ca(2+) load during high work states in 7-week AS myocytes. In hypertrophied failing mouse myocytes, depressed contractile reserve is related to an impaired augmentation of systolic [Ca(2+)](i) and SR Ca(2+) load and simulates findings in human failing myocytes.

Non-NASA Center↗
NASA NTRS2000

Left ventricular hypertrophy in ascending aortic stenosis mice: anoikis and the progression to early failure

BACKGROUND: To determine potential mechanisms of the transition from hypertrophy to very early failure, we examined apoptosis in a model of ascending aortic stenosis (AS) in male FVB/n mice. METHODS AND RESULTS: Compared with age-matched controls, 4-week and 7-week AS animals (n=12 to 16 per group) had increased ratios of left ventricular weight to body weight (4.7+/-0.7 versus 3.1+/-0.2 and 5. 7+/-0.4 versus 2.7+/-0.1 mg/g, respectively, P<0.05) with similar body weights. Myocyte width was also increased in 4-week and 7-week AS mice compared with controls (19.0+/-0.8 and 25.2+/-1.8 versus 14. 1+/-0.5 microm, respectively, P<0.01). By 7 weeks, AS myocytes displayed branching with distinct differences in intercalated disk size and staining for beta(1)-integrin on both cell surface and adjacent extracellular matrix. In vivo left ventricular systolic developed pressure per gram as well as endocardial fractional shortening were similar in 4-week AS and controls but depressed in 7-week AS mice. Myocyte apoptosis estimated by in situ nick end-labeling (TUNEL) was extremely rare in 4-week AS and control mice; however, a low prevalence of TUNEL-positive myocytes and DNA laddering were detected in 7-week AS mice. The specificity of TUNEL labeling was confirmed by in situ ligation of hairpin oligonucleotides. CONCLUSIONS: Our findings indicate that myocyte apoptosis develops during the transition from hypertrophy to early failure in mice with chronic biomechanical stress and support the hypothesis that the disruption of normal myocyte anchorage to adjacent extracellular matrix and cells, a process called anoikis, may signal apoptosis.

NASA Discipline Cardiopulmonary↗
NASA NTRS2000

TAK1 is activated in the myocardium after pressure overload and is sufficient to provoke heart failure in transgenic mice

The transforming-growth-factor-beta-activated kinase TAK1 is a member of the mitogen-activated protein kinase kinase kinase family, which couples extracellular stimuli to gene transcription. The in vivo function of TAK1 is not understood. Here, we investigated the potential involvement of TAK1 in cardiac hypertrophy. In adult mouse myocardium, TAK1 kinase activity was upregulated 7 days after aortic banding, a mechanical load that induces hypertrophy and expression of transforming growth factor beta. An activating mutation of TAK1 expressed in myocardium of transgenic mice was sufficient to produce p38 mitogen-activated protein kinase phosphorylation in vivo, cardiac hypertrophy, interstitial fibrosis, severe myocardial dysfunction, 'fetal' gene induction, apoptosis and early lethality. Thus, TAK1 activity is induced as a delayed response to mechanical stress, and can suffice to elicit myocardial hypertrophy and fulminant heart failure.

NASA Discipline Cardiopulmonary↗
NASA NTRS2013

Label-Free Detection of Cardiac Troponin-I Using Carbon Nanofiber Based Nanoelectrode Arrays

A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. A carbon nanofiber (CNF) multiplexed array has been fabricated with 9 sensing pads, each containing 40,000 carbon nanofibers as nanoelectrodes. Here, we report the use of vertically aligned CNF nanoelectrodes for the detection of cardiac Troponin-I for the early diagnosis of myocardial infarction. Antibody, antitroponin, probe immobilization and subsequent binding to human cardiac troponin-I were characterized using electrochemical impedance spectroscopy and cyclic voltammetry techniques. Each step of the modification process resulted in changes in electrical capacitance or resistance to charge transfer due to the changes at the electrode surface upon antibody immobilization and binding to the specific antigen. This sensor demonstrates high sensitivity, down to 0.2 ng/mL, and good selectivity making this platform a good candidate for early stage diagnosis of myocardial infarction.

cardiac output↗
NASA NTRS1994

Altered baroreflex control of forearm vascular resistance during simulated microgravity

Reflex peripheral vasoconstriction induced by activation of cardiopulmonary baroreceptors in response to reduced central venous pressure (CVP) is a basic mechanism for elevating systemic vascular resistance and defending arterial blood pressure during orthostatically-induced reductions in cardiac filling and output. The sensitivity of the cardiopulmonary baroreflex response [defined as the slope of the relationship between changes in forearm vascular resistance (FVR) and CVP] and the resultant vasoconstriction are closely and inversely associated with the amount of circulating blood volume. Thus, a high-gain FVR response will be elicited by a hypovolemic state. Exposure to microgravity during spaceflight results in reduced plasma volume. It is therefore reasonable to expect that the FVR response to cardiopulmonary baroreceptor unloading would be accentuated following adaptation to microgravity. Such data could provide better insight about the physiological mechanisms underlying alterations in blood pressure control following spaceflight. We therefore exposed eleven men to 6 degrees head-down bedrest for 7 days and measured specific hemodynamic responses to low levels of the lower body negative pressure to determine if there are alterations in cardiopulmonary baroreceptor stimulus-FVR reflex response relationship during prolonged exposure to an analog of microgravity.

NASA Program Space Physiology and Countermeasures↗