Self-Generated Lower Body Negative Pressure Exercise: A Low Power Countermeasure for Acute Space Missions.

Microgravity in spaceflight produces headward fluid shifts which probably contribute to Spaceflight-Associated Neuro-Ocular Syndrome (SANS). Developing new methods to mitigate these shifts is crucial for preventing SANS. One possible strategy is the use of self-generated lower body negative pressure (LBNP). This study evaluates biological or physiological effects induced by bed rest to simulate adaptations to microgravity. Participants were tested during powered LBNP and dynamic self-generated (SELF) LBNP at 25 mmHg for 15 min. The results were compared to the physiologic responses observed in seated upright and supine positions without LBNP, which served as controls for normal gravitational effects on fluid dynamics. Eleven participants' (five male, six female) heart rates, blood pressures, and cross-sectional areas (CSA) of left and right internal jugular veins (IJV) were monitored. Self-generated LBNP, which requires mild to moderate physical activity, significantly elevated heart rate and blood pressure (p < 0.01). Self-generated LBNP also significantly reduced right IJV CSA compared to supine position (p = 0.005), though changes on the left side were not significant (p = 0.365). While the effects of SELF and traditional LBNP on IJV CSA were largely similar, traditional LBNP significantly reduced IJV CSA on both sides. Given its low mass, volume, and power requirements, SELF LBNP is a promising countermeasure against SANS. Results from this study warrant longer-term studies of SELF LBNP under simulated spaceflight conditions.

Respiratory Event-Induced Blood Pressure Oscillations Vary by Sleep Stage in Sleep Apnea Patients.

Obstructive sleep apnea (OSA) pathologically stresses the cardiovascular system. Apneic events cause significant oscillatory surges in nocturnal blood pressure (BP). Trajectories of these surges vary widely. This variability challenges the quantification, characterization, and mathematical modeling of BP surge dynamics. We present a method of aggregating trajectories of apnea-induced BP surges using a sample-by-sample averaging of continuously recorded BP. We applied the method to recordings of overnight BP (average total sleep time: 4.77 ± 1.64 h) for 10 OSA patients (mean AHI: 63.5 events/h; range: 18.3-105.4). We studied surges in blood pressure due to obstructive respiratory events separated from other such events by at least 30 s (274 total events). These events increased systolic (SBP) and diastolic (DBP) BP by 19 ± 7.1 mmHg (14.8%) and 11 ± 5.6 mmHg (15.5%), respectively, relative to mean values during wakefulness. Further, aggregated SBP and DBP peaks occurred on average 9 s and 9.5 s after apnea events, respectively. Interestingly, the amplitude of the SBP and DBP peaks varied across sleep stages, with mean peak ranging from 128.8 ± 12.4 to 166.1 ± 15.5 mmHg for SBP and from 63.1 ± 8.2 to 84.2 ± 9.4 mmHg for DBP. The aggregation method provides a high level of granularity in quantifying BP oscillations from OSA events and may be useful in modeling autonomic nervous system responses to OSA-induced stresses.

Quantification of Nocturnal Blood Pressure Oscillations Induced by Sleep Disordered Breathing.

We present an approach to quantifying nocturnal blood pressure (BP) variations that are elicited by sleep disordered breathing (SDB). A sample-by-sample aggregation of the dynamic BP variations during normal breathing and BP oscillations prompted by apnea episodes is performed. This approach facilitates visualization and analysis of BP oscillations. Preliminary results from analysis of a full night study of 7 SDB subjects (5 Male 2 Female, 52±5.6 yrs., Body Mass Index 36.4±7.4 kg/m2, Apnea-Hypopnea Index 69.1±26.8) are presented. Aggregate trajectory and quantitative values for changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) concomitant with obstructive apnea episodes are presented. The results show 19.4 mmHg (15.3%) surge in SBP and 9.4 mmHg (13.6%) surge in DBP compared to their respective values during normal breathing (p<0.05). Further, the peak of the surge in SBP and DBP occurred about 9s and 7s, respectively, post the end of apnea events. The return of SBP and DBP to baseline values displays a decaying oscillatory pattern.

Estimation of cerebral blood flow velocity during breath-hold challenge using artificial neural networks.

The effect of untreated Obstructive Sleep Apnoea (OSA) on cerebral haemodynamics and CA impairment is an active field of research interest. A breath-hold challenge is usually used in clinical and research settings to simulate cardiovascular and cerebrovascular changes that mimic OSA events. This work utilises temporal arterial oxygen saturation (SpO2) and photoplethysmography (PPG) signals to estimate the temporal cerebral blood flow velocity (CBFv) waveform. Measurements of CBFv, SpO2, and PPG, were acquired concurrently from volunteers performing two different protocols of breath-hold challenge in the supine position. Past values of the SpO2 and PPG signals were used to estimate the current values of CBFv using different permutations and topologies of supervised learning with shallow artificial neural networks (ANNs). The measurements from one protocol were used to train the ANNs and find the optimum topologies, which in turn were tested using the other protocol. Data collected from 10 normotensive, healthy subjects (four females, age 28.5 ±â€¯6.1 years, Body Mass Index (BMI) 24.0 ±â€¯4.7 kg/m2) were used in this study. The results show that different subjects have different optimum topologies for ANNs, thus indicating the effects of inter-subject variability on ANNs. Successfully reconstructed blind waveforms for the same subject group in the second protocol showed a reasonable accuracy of 60-80% estimation compared to the measured waveforms. HYPOTHESIS: Temporal waveforms for SpO2 and PPG contain adequate information to estimate the temporal CBFv waveform using ANNs. METHODOLOGY: Concurrent measurements of SpO2 and PPG using pulse oximetry from the forehead and CBFv from the middle cerebral artery (MCA) using transcranial Doppler (TCD) were recorded from healthy, normotensive subjects performing a breath-hold challenge. The breath-hold challenge mimicked the cerebrovascular response to apnoea, and was recorded by measuring CBFv in MCA. Two protocols were used, each consisting of five breath-holding manoeuvres and differing in terms of the time between the five successive breath-holds. Using data from one protocol, several permutations of the temporal values of SpO2 and PPG signals were used as inputs to different ANN topologies, in order to train and find the optimum model. The optimum model was evaluated using the data from the other protocol as a blind dataset. RESULTS: Using the first protocol for training, optimum ANN configurations were found to be different for each subject, and accuracy of 75-87% was achieved. When these optimum ANN models were tested using the second protocol as a blind dataset, the accuracy achieved was around 60-80%. CONCLUSIONS: A novel approach employing temporal records of SpO2 and PPG can be used to estimate the CBFv waveform using ANNs with acceptable accuracy. Increases in the size and diversity of the population dataset and the use of features extracted from SpO2 and PPG signals are needed for generalisation of the method and potential future clinical applications.

Dynamic Estimation of Cerebral Blood Flow Using Blood Pressure Signal in sleep Apnea Patients.

Monitoring apnea-induced cerebral blood flow (CBF) oscillations is of importance for assessing apnea patient brain health. Blood pressure (BP) oscillations during apnea can induce oscillations in CBF. Preliminary results of testing an Auto Regressive Moving Average model relating nocturnal CBP oscillations to nocturnal BP variations in 8 obstructive sleep apnea subjects (3 F, 55±8 yrs., BMI 34.2±7.85 kg/m2) showed that largest mean and standard deviation of the CBF estimation errors was 4.49±7.57 cm/s and maximum root mean squared of the errors was 8.80 cm/s. Hence, reasonable accuracy in estimating CBF from BP during sleep apnea events was observed.

Dynamic Estimation of Cerebral Blood Flow Using Photoplethysmography Signal during Simulated Apnea.

Monitoring apnea-induced cerebral blood flow oscillations is of importance for assessing apnea patient brain health. Using an autoregressive moving average model, peak and trough values of cerebral blood flow were estimated from a concurrently recorded forehead photoplethysmography signal. Preliminary testing of the method in 7 subjects (4 F, 32±4 yrs., BMI 24.57±3.87 kg/m2) using a breath hold paradigm for simulating apnea shows that maximum mean and standard deviation of the prediction error is -1.10±8.49 cm/s and the maximum root mean squared of the error is 8.92 cm/s.

Mathematical Modeling of Arterial Blood Pressure Using Photo- Plethysmography Signal in Breath-hold Maneuver.

recent research has shown that each apnea episode results in a significant rise of the beat-to-beat blood pressure followed by a drop to the pre-episode levels when patient resumes normal breathing. While the physiological implications of these repetitive and significant oscillations are still unknown, it is of interest to quantify them. Since current array of instruments deployed for polysomnography studies does not include beat-to-beat measurement of blood pressure, but includes oximetry which can supply pulsatile photoplethysmography (PPG) signal, in addition to percent oxygen saturation. Hence, we have investigated a new method for continuous estimation of systolic (SBP), diastolic (DBP), and mean (MBP) blood pressure waveforms from PPG. Peaks and troughs of PPG waveform are used as input to a 5th order autoregressive moving average model to construct estimates of SBP, DBP, and MBP waveforms. Since breath hold maneuvers are shown to faithfully simulate apnea episodes, we evaluated the performance of the proposed method in 7 subjects (4 F; $32 \pm 4$ yrs., BMI $24.57 \pm 3.87$ kg/m2) in supine position doing 5 breath holding maneuvers with 90s of normal breathing between them. The modeling error ranges were (all units are in mmHg $) 0.88 \pm 4.87$ to $- 2.19 \pm 5.73($ SBP); $0.29 \pm 2.39$ to $- 0.97 \pm 3.83($ DBP); and $- 0.42 \pm 2.64$ to $- 1.17 \pm 3.82($ MBP). The cross validation error ranges were $0.28 \pm 6.45$ to $- 1.74 \pm 6.55($ SBP); $0.09 \pm 3.37$ to $0.97 \pm 3.67($ DBP); and $0.33 \pm 4.34$ to $- 0.87 \pm 4.42($ MBP). The overall level of estimation error, as measured by the root mean squared of the model residuals, was less than 7 mmHg.

Arterial blood pressure feature estimation using photoplethysmography.

Continuous and noninvasive monitoring of blood pressure has numerous clinical and fitness applications. Current methods of continuous measurement of blood pressure are either invasive and/or require expensive equipment. Therefore, we investigated a new method for the continuous estimation of two main features of blood pressure waveform: systolic and diastolic pressures. The estimates were obtained from a photoplethysmography signal as input to the fifth order autoregressive moving average models. The performance of the method was evaluated using beat-to-beat full-wave blood pressure measurements from 15 young subjects, with no known cardiovascular disorder, in supine position as they breathed normally and also while they performed a breath-hold maneuver. The level of error in the modeling and prediction estimates during normal breathing and breath-hold maneuvers, as measured by the root mean square of the residuals, were less than 5 mmHg and 11 mm Hg, respectively. The mean of model residuals both during normal breathing and breath-hold maneuvers was considered to be less than 3.2 mmHg. The dependency of the accuracy of the estimates on the subject data was assessed by comparing the modeling errors for the 15 subjects. Less than 1% of the models showed significant differences (p < 0.05) from the other models, which indicates a high level of consistency among the models.

Phantom study evaluating detection of simulated upper airway occlusion using piezoelectric ultrasound transducers.

Obstructive sleep apnea/hypopnea syndrome (OSAHS) is characterized by repetitive narrowing or full collapse of the upper airway concomitant with continued respiratory effort during sleep lasting 10s or more. OSAHS is the most prevalent form of sleep-disordered breathing, affecting more than 17% of the middle-aged U.S. POPULATION: Hence, many individuals need to be tested for having OSAHS. Currently, detection of airway occlusion due to OSAHS is achieved by indirect measurements, often requiring multiple sensor types, such as a flow transducer combined with chest and abdomen plethysmography. The need for the use of multiple sensors in the current OSAHS detection systems adds to the cost and complexity of the current systems and associated procedures. Development of a simple sensor system that allows direct detection of airway occlusion is advantageous, as it simplifies detection of OSAHS and paves the way for home diagnosis of OSAHS. The utilization of ultrasonic transducers is attractive, as it is non-invasive and non-ionizing. We present a new ultrasound sensing system for direct detection of the occlusion in the upper airway in OSAHS patients during sleep. The system takes into consideration the constraints arising from the location of probing and the acoustic requirements for transducers. The physiological and theoretical backgrounds are presented for using ultrasonic pulses to detect the presence and degree of occlusion in the airway. The proposed methodology for creating an anthropomorphically-correct neck and airway phantoms to test the hypothesis and the results of the tests are presented. HYPOTHESIS: An ultrasonic signal transmitted through or reflected from an open airway will have different features compared to those associated with a partially or fully occluded airway. METHODOLOGY: A system, comprising a phantom model of the airway and neck with the approximate anatomical-correct dimensions and acoustic properties of the airway, is designed and built. It allows simulating fully open airway as well as hypopnea and apnea events. Further, it facilitates probing using multiple ultrasonic frequencies and transducer configurations for use with different neck sizes. Ultrasound waves are generated using a piezoelectric source to the model of the airway and received by piezoelectric receivers on the opposite side. Energy, the area under the curve, and the peak value of the received signal, are used to detect the airway occlusion. RESULTS: The amount of reflected ultrasonic energy from the phantom model of the airway back to the transmitting transducer reduces as the airway model occlusion increases. Also, transmitted signal through the airway model increases as the amount occlusion of the airway model increases. CONCLUSIONS: The results of this study support the hypothesis that it is feasible to use ultrasonic pulses to detect partial and full upper airway occlusion.

Rapid-eye-movement sleep-predominant central sleep apnea relieved by positive airway pressure: a case report.

Central Sleep Apnea (CSA) is characterized by intermittent apneas and hypopneas during sleep that result from absent central respiratory drive. CSA occurs almost exclusively during non-rapid-eye-movement (NREM) sleep due to enhanced neuronal ventilatory drive during REM sleep that makes central apneas highly unlikely to form. A 45-year-old obese African American female presented with co-existing Obstructive Sleep Apnea (OSA) and CSA, not in the form of mixed or complex sleep apnea. Peculiarly, her CSA occurred only during rapid-eye-movement (REM) sleep, which is exceedingly rare. The patient's CSA was resolved when appropriate positive airway pressure (PAP) was prescribed. Our patient remains stable and has reported significant benefit from PAP usage. We offer possible neuro-physiological mechanisms herein, including enhanced loop gain and/or malfunction or malformation of the pre-Botzinger nucleus or other neurological process, that could explain the unique findings of this case.

Treadmill exercise within lower body negative pressure protects leg lean tissue mass and extensor strength and endurance during bed rest.

Leg muscle mass and strength are decreased during reduced activity and non-weight-bearing conditions such as bed rest (BR) and spaceflight. Supine treadmill exercise within lower body negative pressure (LBNPEX) provides full-body weight loading during BR and may prevent muscle deconditioning. We hypothesized that a 40-min interval exercise protocol performed against LBNPEX 6 days week(-1) would attenuate losses in leg lean mass (LLM), strength, and endurance during 6° head-down tilt BR, with similar benefits for men and women. Fifteen pairs of healthy monozygous twins (8 male and 7 female pairs) completed 30 days of BR with one sibling of each twin pair assigned randomly as the non-exercise control (CON) and the other twin as the exercise subject (EX). Before and after BR, LLM and isokinetic leg strength and endurance were measured. Mean knee and ankle extensor and flexor strength and endurance and LLM decreased from pre- to post-BR in the male CON subjects (P < 0.01), but knee extensor strength and endurance, ankle extensor strength, and LLM were maintained in the male EX subjects. In contrast, no pre- to post-BR changes were significant in the female subjects, either CON or EX, likely due to their lower pre-BR values. Importantly, the LBNPEX countermeasure prevents or attenuates declines in LLM as well as extensor leg strength and endurance. Individuals who are stronger, have higher levels of muscular endurance, and/or have greater LLM are likely to experience greater losses during BR than those who are less fit.

WISE 2005: Aerobic and resistive countermeasures prevent paraspinal muscle deconditioning during 60-day bed rest in women.

Microgravity-induced lumbar paraspinal muscle deconditioning may contribute to back pain commonly experienced by astronauts and may increase the risk of postflight injury. We hypothesized that a combined resistive and aerobic exercise countermeasure protocol that included spinal loading would mitigate lumbar paraspinal muscle deconditioning during 60 days of bed rest in women. Sixteen women underwent 60-day, 6° head-down-tilt bed rest (BR) and were randomized into control and exercise groups. During bed rest the control group performed no exercise. The exercise group performed supine treadmill exercise within lower body negative pressure (LBNP) for 3-4 days/wk and flywheel resistive exercise for 2-3 days/wk. Paraspinal muscle cross-sectional area (CSA) was measured using a lumbar spine MRI sequence before and after BR. In addition, isokinetic spinal flexion and extension strengths were measured before and after BR. Data are presented as means ± SD. Total lumbar paraspinal muscle CSA decreased significantly more in controls (10.9 ± 3.4%) than in exercisers (4.3 ± 3.4%; P < 0.05). The erector spinae was the primary contributor (76%) to total lumbar paraspinal muscle loss. Moreover, exercise attenuated isokinetic spinal extension loss (-4.3 ± 4.5%), compared with controls (-16.6 ± 11.2%; P < 0.05). In conclusion, LBNP treadmill and flywheel resistive exercises during simulated microgravity mitigate decrements in lumbar paraspinal muscle structure and spine function. Therefore spaceflight exercise countermeasures that attempt to reproduce spinal loads experienced on Earth may mitigate spinal deconditioning during long-duration space travel.

Analogs of microgravity: head-down tilt and water immersion.

This article briefly reviews the fidelity of ground-based methods used to simulate human existence in weightlessness (spaceflight). These methods include horizontal bed rest (BR), head-down tilt bed rest (HDT), head-out water immersion (WI), and head-out dry immersion (DI; immersion with an impermeable elastic cloth barrier between subject and water). Among these, HDT has become by far the most commonly used method, especially for longer studies. DI is less common but well accepted for long-duration studies. Very few studies exist that attempt to validate a specific simulation mode against actual microgravity. Many fundamental physical, and thus physiological, differences exist between microgravity and our methods to simulate it, and between the different methods. Also, although weightlessness is the salient feature of spaceflight, several ancillary factors of space travel complicate Earth-based simulation. In spite of these discrepancies and complications, the analogs duplicate many responses to 0 G reasonably well. As we learn more about responses to microgravity and spaceflight, investigators will continue to fine-tune simulation methods to optimize accuracy and applicability.

Systolic pressure response to voluntary apnea predicts sympathetic tone in obstructive sleep apnea as a clinically useful index.

The present investigation tested the hypotheses that systolic arterial pressure (SAP) responses to voluntary apnea (a) serve as a surrogate of sympathetic nerve activity (SNA), (b) can distinguish Obstructive Sleep Apnea (OSA) patients from control subjects and (c) can document autonomic effects of treatment. 9 OSA and 10 control subjects were recruited in a laboratory study; 44 OSA subjects and 78 control subjects were recruited in a clinical study; and 21 untreated OSA subjects and 14 well-treated OSA subjects were recruited into a treatment study. Each subject performed hypoxic and room air voluntary apneas in triplicate. Muscle SNA (MSNA) and continuous AP were measured during each apnea in the laboratory study, while systolic arterial pressure (SAP) responses were measured continuously and by standard auscultation in the clinical and treatment studies. OSA subjects exhibited increased mean arterial pressure (MAP), SAP and MSNA responses to hypoxic apnea (all P<0.01) and the SAP response highly correlated with the MSNA response (R(2)=0.72, P<0.001). Clinical assessment confirmed that OSA subjects exhibited markedly elevated SAP responses (P<0.01), while treated OSA subjects had a decreased SAP response to apnea (P<0.04) compared to poorly treated subjects. These data indicate that (a) OSA subjects exhibit increased pressor and MSNA responses to apnea, and that (b) voluntary apnea may be a clinically useful assessment tool of autonomic dysregulation and treatment efficacy in OSA.

Treadmill exercise within lower-body negative pressure attenuates simulated spaceflight-induced reductions of balance abilities in men but not women.

Spaceflight causes sensorimotor adaptations that result in balance deficiencies on return to a gravitational environment. Treadmill exercise within lower-body negative pressure (LBNP) helps protect physiological function during microgravity as simulated by bed rest. Therefore, we hypothesized that treadmill exercise within LBNP would prevent balance losses in both male and female identical twins during 30 days of 6° head-down tilt bed rest. Fifteen (seven female and eight male) identical twin sets participated in this simulation of microgravity. Within each twin pair, one twin was randomly assigned to an exercise group that performed 40 min of supine treadmill exercise within LBNP set to generate 1.0-1.2 body weight, followed by 5 min of static feet-supported LBNP, 6 days per week. Their identical sibling was assigned to a non-exercise control group with all other bed rest conditions equivalent. Before and immediately after bed rest, subjects completed standing and walking rail balance tests with eyes open and eyes closed. In control subjects, standing rail balance times (men: -42%, women: -40%), rail walk distances (men: -44%, women: -32%) and rail walk times (men: -34%, women: -31%) significantly decreased after bed rest. Compared with controls, treadmill exercise within LBNP significantly attenuated losses of standing rail balance time by 63% in men, but the 41% attenuation in women was not significant. Treadmill exercise within LBNP did not affect rail walk abilities in men or women. Treadmill exercise within LBNP during simulated spaceflight attenuates loss of balance control in men but not in women.

Dynamic modeling of apnea induced concurrent variations in arterial blood pressure and cerebral blood flow velocity.

Obstructive Sleep Apnea (OSA) is characterized by partial (hypopnea) or complete cessation (apnea) of airflow to the lungs during sleep. It has been previously reported that apnea episodes lead to significant rise in instantaneous blood pressure concomitant with a rise in cerebral blood flow velocity, indicating loss of cerebral autoregulation during the episodes. In this study, we have used Auto Regressive Moving Average model (ARMA (na, nb, nk)) to quantify OSA induced dynamic changes in cerebral blood flow velocity (CBFV) with beat to beat blood pressure (BP) as an input. BP and CBFV were recorded from 11 positively diagnosed sleep apnea subjects (6 Males, 5 Females; Age: 54.27±6.23 years, BMI:34.95±7.06kg/m2, AHI: 57.39±28.43). The results suggest that two separate models, ARMA (5, 9, 1) and ARMA (5, 10, 0) can be used to quantify dynamic CBFV variations during apneas with a duration of less than and greater than 30s respectively with reasonable accuracy (<;6% error).

A study of apnea induced covariations of cerebral blood flow and exhaled CO2.

Sleep apnea is identified by repetitive reduction or complete cessation of breathing during sleep. Sleep apnea affects cerebral hemodynamics and it is important to study this effect. Measuring cerebral blood flow during sleep is challenging due to the need to maintain a contact between the flow probe and the skull. It is hypothesized that there exists a relationship between the variations in the exhaled CO2 and Cerebral Blood Flow during sleep apnea. To test this hypothesis, the present study was conducted in two parts: simulated and nocturnal sleep study. 9 volunteer subjects (6 Male and 3 Female Age: 23.11±1.59 years BMI: 21.9±2.409kg/m2) participated in the simulated study and 10 volunteer subjects (9 Male and 1 Female Age: 50.2±7.48 years BMI: 31.541±4.56 kg/m2 AHI: 62.84±20.44) participated in a nocturnal sleep study. Analyzing full waveforms of cerebral blood flow velocity (CBFV) and exhaled CO2, the relationship between 4 metrics from CBFV and 2 metrics from exhaled CO2 were investigated. Although one metric pair showed statistically significant and relatively high correlation (ρ= 0.68 p=7.96×10-7) during the simulated study, the same was not observed during the nocturnal study. Therefore, the proposed hypothesis could not be proven.

Interactive effects of hypoxia, hypercapnia and lung volume on sympathetic nerve activity in humans.

NEW FINDINGS: What is the central question of this study? The central question of this study was to investigate the interaction of mild exposures to O2 and CO2 on chemoreflex control of SNA and the modulation of lung volume and respiratory phase on this interaction. What is the main finding and its importance? We demonstrate that the synergistic interaction of oxygen- and carbon dioxide-chemosensitive control of the sympathetic nervous system with hypoxia and hypercapnia exists at very mild excitatory stimuli, is significantly overridden by lung inflation and does not extend to inhibitory modulation by hypocapnia in healthy subjects. These findings demonstrate the important inhibitory modulation of sympathetic nerve activity by lung inflation mechanisms in healthy individuals even in the presence of strong sympathoexcitatory stimuli. We hypothesized that simultaneous stimulation of O2 - and CO2 -sensitive chemoreflexes produces synergistic activation of the sympathetic nervous system and that this effect would be most apparent at low lung volume (expiratory) phases of respiration. Each subject (n = 11) breathed 16 gas mixtures in random order: a 4 × 4 matrix of normoxic to hypoxic (8, 12, 16 and 21% O2 ) combined with normocapnic to hypercapnic gases (0, 2, 4 and 6% CO2). Tidal volume, arterial pressure, heart rate and muscle sympathetic nerve activity (MSNA) were measured continuously before and while breathing each gas mixture for 2 min. Changes in MSNA were determined for each gas mixture. The MSNA was subdivided into low and high lung volume and respiratory phases to investigate further modulation by components of normal respiratory phase. Both hypoxia and hypercapnia increased mean MSNA independently. Mean and low lung volume MSNA increased exponentially with increasing levels of combined hypoxia and hypercapnia and resulted in a significant interaction (P < 0.01). In contrast, MSNA during the high lung volume phase of respiration never increased significantly (P > 0.4). Similar but less pronounced effects were found for expiratory and inspiratory phases of respiration. These effects created marked respiratory periodicity in MSNA at higher levels of combined hypoxia and hypercapnia. Finally, the response to hypoxia was not affected by hypocapnia, suggesting that the interaction occurs only during excitatory chemosensitive stimuli. These data indicate that hypoxia and hypercapnia interact to elicit synergistic sympathoexcitation and that withdrawal of sympathoinhibitory effects of lung inflation exaggerates this chemoreflex interaction.

WISE-2005: Countermeasures to prevent muscle deconditioning during bed rest in women.

The objectives of this study were to evaluate the efficacy of two separate countermeasures, exercise and protein supplementation, to prevent muscle strength and lean tissue mass losses during 60 days of bed rest (BR) in women and whether countermeasure efficacy was influenced by pre-BR muscular fitness (strength, endurance, tissue mass). Twenty-four women were assigned to an exercise (EX, n = 8), a no-exercise control (CON, n = 8), or a no-exercise protein supplementation group (PROT, n = 8). EX performed supine treadmill exercise within lower body negative pressure 3-4 days/wk and maximal concentric and eccentric supine leg- and calf-press exercises 2-4 days/wk. PROT consumed a diet with elevated protein content compared with CON and EX (1.6 vs. 1.0 g·kg(-1)·day(-1)). Knee and calf isokinetic strength and endurance, isotonic leg-press strength, and leg lean mass were measured before and after BR. Post-BR knee extensor strength and endurance, ankle strength, and leg lean mass were significantly greater and leg-press strength tended to be higher in EX than in CON and PROT. Post-BR measures in PROT were not different than those in CON. Exercise countermeasure efficacy was less, and strength, endurance, and leg lean mass losses in CON and PROT were greater, in subjects who were more fit pre-BR. An exercise protocol combining resistive and aerobic exercise training protects against losses in strength, endurance, and leg lean mass in women during BR, while a nutritional countermeasure without exercise was not effective. Exercise countermeasures may require individualization to protect higher levels of strength and endurance.