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NASA NTRS2008

Validation of Cardiovascular Parameters During NASA's Functional Task Test

Microgravity-induced physiological changes, including cardiovascular deconditioning may impair crewmembers f capabilities during exploration missions on the Moon and Mars. The Functional Task Test (FTT), which will be used to assess task performance in short and long duration astronauts, consists of 7 functional tests to evaluate crewmembers f ability to perform activities to be conducted in a partial-gravity environment or following an emergency landing on Earth. The Recovery from Fall/Stand Test (RFST) tests both the subject fs ability to get up from a prone position and orthostatic intolerance. PURPOSE: Crewmembers have never become presyncopal in the first 3 min of quiet stand, yet it is unknown whether 3 min is long enough to cause similar heart rate fluctuations to a 5-min stand. The purpose of this study was to validate and test the reliability of heart rate variability (HRV) analysis of a 3-min quiet stand. METHODS: To determine the validity of using 3 vs. 5-min of standing to assess HRV, 7 healthy subjects remained in a prone position for 2 min, stood up quickly and stood quietly for 6 min. ECG and continuous blood pressure data were recorded. Mean R-R interval and spectral HRV were measured in minutes 0-3 and 0-5 following the heart rate transient due to standing. Significant differences between the segments were determined by a paired t-test. To determine the reliability of the 3-min stand test, 13 healthy subjects completed 3 trials of the complete FTT on separate days, including the RFST with a 3-min stand test. Analysis of variance (ANOVA) was performed on the HRV measures. RESULTS: Spectral HRV measures reflecting autonomic activity were not different (p>0.05) during the 0-3 and 0-5 min segment (mean R-R interval: 738+/-74 ms, 728+/-69 ms; low frequency to high frequency ratio: 6.5+/-2.2, 7.7+/-2.7; normalized high frequency: 0.19+/-0.03, 0.18+/-0.04). The average coefficient of variation for mean R-R interval, systolic and diastolic blood pressures in the prone position and stand test were less than 8% for the test sessions. ANOVA results yielded a greater inter-subject variability (p.0.006) than inter-session variability (p>0.05) for HRV in the stand test. CONCLUSION: These studies show that a 3 minute stand delivers repeatable cardiovascular heart rate and BP data in the context of this larger series of tests such as the FTT.

Arzeno, N. M.↗
NASA NTRS2009

Validation of Cardiovascular Parameters during NASA's Functional Task Test

Microgravity exposure causes physiological deconditioning and impairs crewmember task performance. The Functional Task Test (FTT) is designed to correlate these physiological changes to performance in a series of operationally-relevant tasks. One of these, the Recovery from Fall/Stand Test (RFST), tests both the ability to recover from a prone position and cardiovascular responses to orthostasis. PURPOSE: Three minutes were chosen for the duration of this test, yet it is unknown if this is long enough to induce cardiovascular responses similar to the operational 5 min stand test. The purpose of this study was to determine the validity and reliability of heart rate variability (HRV) analysis of a 3 min stand and to examine the effect of spaceflight on these measures. METHODS: To determine the validity of using 3 vs. 5 min of standing to assess HRV, ECG was collected from 7 healthy subjects who participated in a 6 min RFST. Mean R-R interval (RR) and spectral HRV were measured in minutes 0-3 and 0-5 following the heart rate transient due to standing. Significant differences between the segments were determined by a paired t-test. To determine the reliability of the 3-min stand test, 13 healthy subjects completed 3 trials of the FTT on separate days, including the RFST with a 3 min stand. Analysis of variance (ANOVA) was performed on the HRV measures. One crewmember completed the FTT before a 14-day mission, on landing day (R+0) and one (R+1) day after returning to Earth. RESULTS VALIDITY: HRV measures reflecting autonomic activity were not significantly different during the 0-3 and 0-5 min segments. RELIABILITY: The average coefficient of variation for RR, systolic (SBP) and diastolic blood pressures during the RFST were less than 8% for the 3 sessions. ANOVA results yielded a greater inter-subject variability (p<0.006) than inter-session variability (p>0.05) for HRV in the RFST. SPACEFLIGHT: Lower RR and higher SBP were observed on R+0 in rest and stand. On R+1, both RR and SBP trended towards preflight rest and stand values. Postflight HRV showed higher LF/HF for rest and stand and lower HFnu during rest. CONCLUSION: These studies show that a 3 min stand delivers repeatable HRV data in the context of this larger series of FTT tests. Spaceflight-induced changes in blood pressure, RR and autonomic function (HRV) are evident from the RFST.

Arzeno, N. M.↗
NASA NTRS2009

Splanchnic Compression Improves the Efficacy of Compression Stockings to Prevent Orthostatic Intolerance

Purpose: Post-spaceflight orthostatic intolerance (OI) is observed in 20-30% of astronauts. Previous data from our laboratory suggests that this is largely a result of decreased venous return. Currently, NASA astronauts wear an anti-gravity suit (AGS) which consists of inflatable air bladders over the calves, thighs and abdomen, typically pressurized from 26 to 78 mmHg. We recently determined that, thigh-high graded compression stockings (JOBST , 55 mmHg at ankle, 6 mmHg at top of thigh) were effective, though to a lesser degree than the AGS. The purpose of this study was to evaluate the addition of splanchnic compression to prevent orthostatic intolerance. Methods: Ten healthy volunteers (6M, 4F) participated in three 80 head-up tilts on separate days while (1) normovolemic (2) hypovolemic w/ breast-high compression stockings (BS)(JOBST(R), 55 mmHg at the ankle, 6 mmHg at top of thigh, 12 mmHg over abdomen) (3) hypovolemic w/o stockings. Hypovolemia was induced by IV infusion of furosemide (0.5 mg/kg) and 48 hrs of a low salt diet to simulate plasma volume loss following space flight. Hypovolemic testing occurred 24 and 48 hrs after furosemide. One-way repeated measures ANOVA, with Bonferroni corrections, was used to test for differences in blood pressure and heart rate responses to head-up tilt, stand times were compared using a Kaplan-Meyer survival analysis. Results: BS were effective in preventing OI and presyncope in hypovolemic test subjects ( p = 0.015). BS prevented the decrease in systolic blood pressure seen during tilt in normovolemia (p < 0.001) and hypovolemia w/o countermeasure (p = 0.005). BS also prevented the decrease in diastolic blood pressure seen during tilt in normovolemia (p = 0.006) and hypovolemia w/o countermeasure (p = 0.041). Hypovolemia w/o countermeasure showed a higher tilt-induced heart rate increase (p = 0.022) than seen in normovolemia; heart rate while wearing BS was not different than normovolemia (p = 0.353). Conclusion: BS may be an effective countermeasure to post-space flight OI. The addition of splanchnic compression is more effective than the previous thigh-high garments. These stockings are readily available, inexpensive, and can be worn for days following landing as astronauts re-adapt to Earth gravity.

Platts, Steven H.↗
NASA NTRS2009

Gender Differences in Baroreflex Sensitivity after Bed Rest

Two potential contributing factors to post-spaceflight orthostatic intolerance are decreases in baroreflex sensitivity (BRS) and sympathetic nervous system response. The purpose of this study was to examine the shape of the BRS curve and sympathetic response to a wide range of blood pressures (BP) before and during 6 head-down bed rest (BR). METHODS: Normal volunteers were tested one day before BR (20M, 1 0F) and near BR days 30 (20M, 10F), 60 (16M, 8F), and 90 (1 0M, 5F). BP was pharmacologically manipulated by 10-min infusions of phenylephrine (PE) and sodium nitroprusside (SNP) at 3 increasing concentrations with a 20-min rest between PE and SNP. Electrocardiogram and continuous finger blood pressure were recorded. A blood sample was drawn at the end of each infusion to measure plasma norepinephrine levels. The spontaneous baroreflex slope (SBS), a measure of BRS, was calculated as the slope of a sequence of 3 or more beats in which the systolic BP (SBP) and following R-R interval (RR) both increased or decreased. The data included saturated responses at the upper but not the lower end of the BP range. Mean response curves were constructed using second-order mixed model analysis. Results are based on term significance in the models. RESULTS RR: RR was lower during BR than pre BR (p<0.001). Pre BR males were modeled by a linear RR response to SBP (p=0.000) while females had a quadratic response which saturated at high SBP (p=0.019). By day 30, both genders were modeled by a linear response; compared to males, females had an attenuated (lower slope) RR response to changes in SBP (p=0.031). SBS: SBS vs SBP analysis showed a lower SBS during BR (p<0.001) when compared to pre BR. Females had a higher SBS than males pre BR (p=0.006). Females exhibited saturating SBS at higher SBP (p=0.016) on day 30, while males were modeled by a linear SBS response to SBP (p=0.035). NE: Females had different NE response to diastolic BP than males pre BR (p=0.035) and on day 30 (p=0.005). CONCLUSION: NE, RR and SBS responses to BP are affected by gender and BR. Not only do gender and BR baseline differences exist, but gender and BR also influence the slope and saturation of the BRS curves. Attenuated and saturating RR and SBS responses, as well as differences in baseline values, may contribute to the higher rates of orthostatic intolerance in women and after bed rest.

Arzeno, Natalia M.↗
NASA NTRS2010

Midodrine as a Countermeasure to Orthostatic Hypotension Immediately After Space Shuttle Landing

Midodrine prevents post-space flight orthostatic intolerance when testing is conducted in a controlled laboratory setting within 2-4 hours after Space Shuttle landing. It is unknown if midodrine is as effective during re-entry and immediately following landing. METHODS: Cardiovascular responses to 10 minutes of 80 head-up tilt in five male astronauts were compared before and immediately after Space Shuttle missions. Preflight tests were conducted in the Johnson Space Center Cardiovascular Laboratory without midodrine. Post-flight testing was performed in the Crew Transport Vehicle on the Space Shuttle runway within 60 minutes of landing; midodrine was self-administered before re-entry. Survival analysis was performed (Gehan-Breslow test) to compare presyncope rates pre- to post-flight. Cardiovascular responses (last minute standing minus supine) to tilt before and after space flight were compared using paired t-tests. RESULTS: Midodrine did not prevent post-flight orthostatic hypotension in two of the five astronauts, but the rate of presyncope across the group did not increase (p=0.17) from pre- to post-flight. Also, although the change in heart rate from supine to the last minute of standing was not affected by space flight, systolic blood pressure decreased more (p=0.05) and diastolic blood pressure tended to decrease (p=0.08) after space flight. CONCLUSIONS: Accurate interpretation of the current results requires that similar data be collected in control subjects (without midodrine) on the CTV. However, drug interaction concerns with commonly used anti-emetics and potentiation of prolonged QTc intervals observed in long duration astronauts make the routine use of midodrine for immediate post-flight orthostatic hypotension unlikely. 2

Platts, Steven H.↗
NASA NTRS2011

Extreme Tele-Echocardiography: Methodology for Remote Guidance of In-flight Echocardiography Aboard the International Space Station

Echocardiography is ideally suited for cardiovascular imaging in remote environments, but the expertise to perform it is often lacking. In 2001, an ATL HDI5000 was delivered to the International Space Station (ISS). The instrument is currently being used in a study to investigate the impact of long-term microgravity on cardiovascular function. The purpose of this report is to describe the methodology for remote guidance of echocardiography in space. Methods: In the year before launch of an ISS mission, potential astronaut echocardiographic operators participate in 5 sessions to train for echo acquisitions that occur roughly monthly during the mission, including one exercise echocardiogram. The focus of training is familiarity with the study protocol and remote guidance procedures. On-orbit, real-time guidance of in-flight acquisitions is provided by a sonographer in the Telescience Center of Mission Control. Physician investigators with remote access are able to relay comments on image optimization to the sonographer. Live video feed is relayed from the ISS to the ground via the Tracking and Data Relay Satellite System with a 2 second transmission delay. The expert sonographer uses these images along with two-way audio to provide instructions and feedback. Images are stored in non-compressed DICOM format for asynchronous relay to the ground for subsequent off-line analysis. Results: Since June, 2009, a total of 19 resting echocardiograms and 4 exercise studies have been performed in-flight. Average acquisition time has been 45 minutes, reflecting 26,000 km of ISS travel per study. Image quality has been adequate in all studies, but remote guidance has proven imperative for fine-tuning imaging and prioritizing views when communication outages limit the study duration. Typical resting studies have included 12 video loops and 21 still-frame images requiring 750 MB of storage. Conclusions: Despite limited crew training, remote guidance allows research-quality echocardiography to be performed by non-experts aboard the ISS. Analysis is underway and additional subjects are being recruited to define the impact of microgravity on cardiac structure and systolic and diastolic function.

Martin, David↗
NASA NTRS2011

Advanced Electrocardiography Can Identify Occult Cardiomyopathy in Doberman Pinschers

Recently, multiple advanced resting electrocardiographic (A-ECG) techniques have improved the diagnostic value of short-duration ECG in detection of dilated cardiomyopathy (DCM) in humans. This study investigated whether 12-lead A-ECG recordings could accurately identify the occult phase of DCM in dogs. Short-duration (3-5 min) high-fidelity 12-lead ECG recordings were obtained from 31 privately-owned, clinically healthy Doberman Pinschers (5.4 +/- 1.7 years, 11/20 males/females). Dogs were divided into 2 groups: 1) 19 healthy dogs with normal echocardiographic M-mode measurements: left ventricular internal diameter in diastole (LVIDd . 47mm) and in systole (LVIDs . 38mm) and normal 24-hour ECG recordings (<50 ventricular premature complexes, VPCs); and 2) 12 dogs with occult DCM: 11/12 dogs had increased M-mode measurements (LVIDd . 49mm and/or LVIDs . 40mm) and 5/11 dogs had also >100 VPCs/24h; 1/12 dogs had only abnormal 24-hour ECG recordings (>100 VPCs/24h). ECG recordings were evaluated via custom software programs to calculate multiple parameters of high-frequency (HF) QRS ECG, heart rate variability, QT variability, waveform complexity and 3-D ECG. Student's t-tests determined 19 ECG parameters that were significantly different (P < 0.05) between groups. Principal component factor analysis identified a 5-factor model with 81.4% explained variance. QRS dipolar and non-dipolar voltages, Cornell voltage criteria and QRS waveform residuum were increased significantly (P < 0.05), whereas mean HF QRS amplitude was decreased significantly (P < 0.05) in dogs with occult DCM. For the 5 selected parameters the prediction of occult DCM was performed using a binary logistic regression model with Chi-square tested significance (P < 0.01). ROC analyses showed that the five selected ECG parameters could identify occult ECG with sensitivity 89% and specificity 83%. Results suggest that 12-lead A-ECG might improve diagnostic value of short-duration ECG in earlier detection of canine DCM as five selected ECG parameters can with reasonable accuracy identify occult DCM in Doberman Pinschers. Future extensive clinical studies need to clarify if 12-lead A-ECG could be useful as an additional screening test for canine DCM.

Spiljak, M.↗
NASA NTRS2011

Femoral Blood Flow and Cardiac Output During Blood Flow Restricted Leg Press Exercise

Low load blood flow restricted resistance exercise (LBFR) causes muscle hypertrophy that may be stimulated by the local ischemic environment created by the cuff pressure. However, local blood flow (BF) during such exercise is not well understood. PURPOSE: To characterize femoral artery BF and cardiac output (CO) during leg press exercise (LP) performed at a high load (HL) and low load (LL) with different levels of cuff pressure. METHODS: Eleven subjects (men/women 4/7, age 31.4+/-12.8 y, weight 68.9+/-13.2 kg, mean+/-SD) performed 3 sets of supine left LP to fatigue with 90 s of rest in 4 conditions: HL (%1-RM/cuff pressure: 80%/0); LL (20%/0); LBFR(sub DBP) (20%/1.3 x diastolic blood pressure, BP); LBFR(sub SBP) (20%/1.3 x supine systolic BP). The cuff remained inflated throughout the LBFR exercise sessions. Artery diameter, velocity time integral (VTI), and stroke volume (SV) were measured using Doppler ultrasound at rest and immediately after each set of exercise. Heart rate (HR) was monitored using a 3-lead ECG. BF was calculated as VTI x vessel cross-sectional area. CO was calculated as HR x SV. The data obtained after each set of exercise were averaged and used for analyses. Multi-level modeling was used to determine the effect of exercise condition on dependent variables. Statistical significance was set a priori at p< 0.05. RESULTS: Artery diameter did not change from baseline. BF increased (p<0.05) after exercise in each condition except LBFR(sub SBP) in the order of HL (12.73+/-1.42 cm3,mean+/-SE) > LL (9.92+/-0.82 cm3) > LBFR(sub dBP)(6.47+/-0.79 cm3) > LBFR(sub SBP) (3.51+/-0.59 cm3). Blunted exercise induced increases occurred in HR, SV, and CO after LBFR compared to HL and LL. HR increased 45% after HL and LL and 28% after LBFR (p<0.05), but SV increased (p<0.05) only after HL. Consequently, the increase (p<0.05) in CO was greater in HL and LL (approximately 3 L/min) than in LBFR (approximately 1 L/min). CONCLUSION: BF during LBFR(sub SBP) was 1/3 of that observed in LL, which supports the hypothesis that local ischemia stimulates the LBFR hypertrophic response. As the cuff did not compress the artery, the ischemia may have occurred because of the blunted rise in CO or because arterial BP cannot overcome the cuff pressure. As LBFR(sub DBP) effectively reduced BF and CO with cuff pressures less than systolic BP, future studies should investigate the hypertrophic potential of LBFR at even lower cuff pressures.

Everett, M. E.↗
NASA NTRS2011

Orthostatic Hypotension After Long-Duration Space Flight: NASA's Experiences from the International Space Station

Our laboratory previously reported that the incidence of orthostatic hypotension (OH) was greater after long- than short-duration spaceflight in astronauts who participated in Mir Space Station and Space Shuttle missions. To confirm and extend these findings, we retrospectively examined tilt test data from International Space Station (ISS) and Shuttle astronauts. We anticipated that the proportion of ISS astronauts experiencing OH would be high on landing day and the number of days to recover greater after long- than short-duration missions. Methods: Twenty ISS and 66 Shuttle astronauts participated in 10-min 80? head-up tilt tests 10 d before launch (L-10), on landing day (R+0) or 1 d after landing (R+1). Data from 5 ISS astronauts tested on R+0 or R+1 who used non-standard countermeasures were excluded. Many astronauts repeated the test 3 d (R+3) after landing. Fisher?s Exact Test was used to compare the ability of ISS and Shuttle astronauts to complete the tilt test on R+0. Cox regression was used to identify cardiovascular parameters that were associated with test completion across all tests, and mixed model analysis was used to compare the change and recovery rates between ISS and Shuttle astronauts. In these analyses, ISS data from R+0 and R+1 were pooled to provide sufficient statistical power. Results: The proportion of astronauts who completed the tilt test on R+0 without OH was less in ISS than in Shuttle astronauts (p=0.03). On R+0, only 2 of 6 ISS astronauts completed the test compared to 53 of 66 (80%) Shuttle astronauts. However, 8 of 9 ISS astronauts completed the test on R+1. On R+3, 13 of 15 (87%) of the ISS and 19 of 19 (100%) of the Shuttle astronauts completed the 10-min test. An index comprised of stroke volume and diastolic blood pressure provided a very good prediction of overall tilt survival. This index was altered by spaceflight similarly for both groups soon after landing (pooled R+0 and R+ 1), but ISS astronauts did not recover at the same rate as Shuttle astronauts (p=0.007). Conclusions: The proportion of ISS astronauts who could not complete the tilt test on R+0 due to OH (4 of 6) is similar to that reported in astronauts who flew on Mir (5 of 6). Further, cardiovascular parameters most closely associated with OH recover more slowly after long- compared to short-duration spaceflight.

Lee, Stuart M. C.↗
NASA NTRS2012

Extreme Tele-Echocardiography: Methodology for Remote Guidance of In-Flight Echocardiography Aboard the International Space Station

Methods: In the year before launch of an ISS mission, potential astronaut echocardiographic operators participate in 5 sessions to train for echo acquisitions that occur roughly monthly during the mission, including one exercise echocardiogram. The focus of training is familiarity with the study protocol and remote guidance procedures. On-orbit, real-time guidance of in-flight acquisitions is provided by a sonographer in the Telescience Center of Mission Control. Physician investigators with remote access are able to relay comments on image quality to the sonographer. Live video feed is relayed from the ISS to the ground via the Tracking and Data Relay Satellite System with a 2- second transmission delay. The expert sonographer uses these images, along with twoway audio, to provide instructions and feedback. Images are stored in non-compressed DICOM format for asynchronous relay to the ground for subsequent off-line analysis. Results: Since June, 2009, a total of 27 resting echocardiograms and 5 exercise studies have been performed during flight. Average acquisition time has been 45 minutes, reflecting 26,000 km of ISS travel per study. Image quality has been adequate in all studies, and remote guidance has proven imperative for fine-tuning imaging and prioritizing views when communication outages limit the study duration. Typical resting studies have included 27 video loops and 30 still-frame images requiring 750 MB of storage. Conclusions: Despite limited crew training, remote guidance allows research-quality echocardiography to be performed by non-experts aboard the ISS. Analysis is underway and additional subjects are being recruited to define the impact of microgravity on cardiac structure and systolic and diastolic function.

Martin, David S.↗
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 NTRS2001

Noninvasive assessment of mitral inertness: clinical results with numerical model validation

Inertial forces (Mdv/dt) are a significant component of transmitral flow, but cannot be measured with Doppler echo. We validated a method of estimating Mdv/dt. Ten patients had a dual sensor transmitral (TM) catheter placed during cardiac surgery. Doppler and 2D echo was performed while acquiring LA and LV pressures. Mdv/dt was determined from the Bernoulli equation using Doppler velocities and TM gradients. Results were compared with numerical modeling. TM gradients (range: 1.04-14.24 mmHg) consisted of 74.0 +/- 11.0% inertial forcers (range: 0.6-12.9 mmHg). Multivariate analysis predicted Mdv/dt = -4.171(S/D (RATIO)) + 0.063(LAvolume-max) + 5. Using this equation, a strong relationship was obtained for the clinical dataset (y=0.98x - 0.045, r=0.90) and the results of numerical modeling (y=0.96x - 0.16, r=0.84). TM gradients are mainly inertial and, as validated by modeling, can be estimated with echocardiography.

NASA Discipline Cardiopulmonary↗
NASA NTRS2001

Evidence for central venous pressure resetting during initial exposure to microgravity

We measured central venous pressure (CVP); plasma volume (PV); urine volume rate (UVR); renal excretion of sodium (UNa); and renal clearances of creatinine, sodium, and osmolality before and after acute volume infusion to test the hypothesis that exposure to microgravity causes resetting of the CVP operating point. Six rhesus monkeys underwent two experimental conditions in a crossover counterbalance design: 1) continuous exposure to 10 degrees head-down tilt (HDT) and 2) a control, defined as 16 h/day of 80 degrees head-up tilt and 8 h prone. After 48 h of exposure to either test condition, a 120-min course of continuous infusion of isotonic saline (0.4 ml. kg(-1). min(-1) iv) was administered. Baseline CVP was lower (P = 0.011) in HDT (2.3 +/- 0.3 mmHg) compared with the control (4.5 +/- 1.4 mmHg) condition. After 2 h of saline infusion, CVP was elevated (P = 0.002) to a similar magnitude (P = 0.485) in HDT (DeltaCVP = 2.7 +/- 0.8 mmHg) and control (DeltaCVP = 2.3 +/- 0.8 mmHg) conditions and returned to preinfusion levels 18 h postinfusion in both treatments. PV followed the same pattern as CVP. The response relationships between CVP and UVR and between CVP and UNa shifted to the left with HDT. The restoration of CVP and PV to lower preinfusion levels after volume loading in HDT compared with control supports the notion that lower CVP during HDT may reflect a new operating point about which vascular volume is regulated. These results may explain the ineffective fluid intake procedures currently employed to treat patients and astronauts.

NASA Discipline Cardiopulmonary↗
NASA NTRS2000

Effects of whole body heating on dynamic baroreflex regulation of heart rate in humans

The purpose of this project was to identify whether dynamic baroreflex regulation of heart rate (HR) is altered during whole body heating. In 14 subjects, dynamic baroreflex regulation of HR was assessed using transfer function analysis. In normothermic and heat-stressed conditions, each subject breathed at a fixed rate (0. 25 Hz) while beat-by-beat HR and systolic blood pressure (SBP) were obtained. Whole body heating significantly increased sublingual temperature, HR, and forearm skin blood flow. Spectral analysis of HR and SBP revealed that the heat stress significantly reduced HR and SBP variability within the high-frequency range (0.2-0.3 Hz), reduced SBP variability within the low-frequency range (0.03-0.15 Hz), and increased the ratio of low- to high-frequency HR variability (all P < 0.01). Transfer function gain analysis showed that the heat stress reduced dynamic baroreflex regulation of HR within the high-frequency range (from 1.04 +/- 0.06 to 0.54 +/- 0.6 beats. min(-1). mmHg(-1); P < 0.001) without significantly affecting the gain in the low-frequency range (P = 0.63). These data suggest that whole body heating reduced high-frequency dynamic baroreflex regulation of HR associated with spontaneous changes in blood pressure. Reduced vagal baroreflex regulation of HR may contribute to reduced orthostatic tolerance known to occur in humans during heat stress.

Non-NASA Center↗
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 NTRS1996

Valsalva's maneuver revisited: a quantitative method yielding insights into human autonomic control

Seventeen healthy supine subjects performed graded Valsalva maneuvers. In four subjects, transesophageal echographic aortic cross-sectional areas decreased during and increased after straining. During the first seconds of straining, when aortic cross-sectional area was declining and peripheral arterial pressure was rising, peroneal sympathetic muscle neurons were nearly silent. Then, as aortic cross-sectional area and peripheral pressure both declined, sympathetic muscle nerve activity increased, in proportion to the intensity of straining. Poststraining arterial pressure elevations were proportional to preceding increases of sympathetic activity. Sympathetic inhibition after straining persisted much longer than arterial and right atrial pressure elevations. Similarly, R-R intervals changed in parallel with peripheral arterial pressure, until approximately 45 s after the onset of straining, when R-R intervals were greater and arterial pressures were smaller than prestraining levels. Our conclusions are as follows: opposing changes of carotid and aortic baroreceptor inputs reduce sympathetic muscle and increase vagal cardiac motor neuronal firing; parallel changes of barorsensory inputs provoke reciprocal changes of sympathetic and direct changes of vagal firing; and pressure transients lasting only seconds reset arterial pressure-sympathetic and -vagal response relations.

NASA Center JSC↗