Oscillations of Hemodynamic Parameters Induced by Negative Pressure Breathing in Healthy Humans.

INTRODUCTION: Negative pressure breathing is breathing with decreased pressure in the respiratory tract without lowering pressure acting on the torso. We lowered air pressure only during inspiration (NPBin). NPBin, used to increase venous return to the heart, is considered a countermeasure against redistribution of body fluids toward the head during spaceflight. We studied NPBin effects on circulation in healthy humans with an emphasis on NPBin-induced oscillations of hemodynamic parameters synchronous with breathing. We propose an approach to analyze the oscillations based on coherent averaging.METHODS: Eight men ages 24-42 yr participated in the NPBin and control series. During the series, to reproduce fluids shift observed under microgravity, subjects were supine and head down (-8°). Duration of NPBin was 20 min, rarefaction -20 cm H2O. Hemodynamic parameters were measured by Finometer. Electrical impedance measurements were used to estimate changes in blood filling of cerebral vessels.RESULTS: Mean values of hemodynamic parameters virtually did not change under NPBin, but NPBin induced oscillations of the parameters synchronous with respiration. Peak-to-peak amplitude under NPBin were: mean arterial pressure, 4 ± 1 (mmHg); stroke volume, 7 ± 3 (mL); and heart rate, 4 ± 1 (bpm). Electrical impedance of the head increased during inspiration. The increase under NPBin was three times greater than under normal breathing.DISCUSSION: Analysis of oscillations gives more information than analysis of mean values. NPBin induces short-term decrease in left ventricle stroke volume and arterial blood pressure during each inspiration; the decrease is compensated by increase after inspiration. NPBin facilitates redistribution of body fluids away from the head.Semenov YS, Melnikov IS, Luzhnov PV, Dyachenko AI. Oscillations of hemodynamic parameters induced by negative pressure breathing in healthy humans. Aerosp Med Hum Perform. 2024; 95(6):297-304.

Segmental Tissue Resistance of Healthy Young Adults during Four Hours of 6-Degree Head-Down-Tilt Positioning.

(1) Background: One effect of microgravity on the human body is fluid redistribution due to the removal of the hydrostatic gravitational gradient. These fluid shifts are expected to be the source of severe medical risks and it is critical to advance methods to monitor them in real-time. One technique to monitor fluid shifts captures the electrical impedance of segmental tissues, but limited research is available to evaluate if fluid shifts in response to microgravity are symmetrical due to the bilateral symmetry of the body. This study aims to evaluate this fluid shift symmetry. (2) Methods: Segmental tissue resistance at 10 kHz and 100 kHz was collected at 30 min intervals from the left/right arm, leg, and trunk of 12 healthy adults over 4 h of 6° head-down-tilt body positioning. (3) Results: Statistically significant increases were observed in the segmental leg resistances, first observed at 120 min and 90 min for 10 kHz and 100 kHz measurements, respectively. Median increases were approximately 11% to 12% for the 10 kHz resistance and 9% for the 100 kHz resistance. No statistically significant changes in the segmental arm or trunk resistance. Comparing the left and right segmental leg resistance, there were no statistically significant differences in the resistance changes based on the side of the body. (4) Conclusions: The fluid shifts induced by the 6° body position resulted in similar changes in both left and right body segments (that had statistically significant changes in this work). These findings support that future wearable systems to monitor microgravity-induced fluid shifts may only require monitoring of one side of body segments (reducing the hardware needed for the system).

Changes in Optic Nerve Head and Retinal Morphology During Spaceflight and Acute Fluid Shift Reversal.

Importance: Countermeasures that reverse the headward fluid shift experienced in weightlessness have the potential to mitigate spaceflight-associated neuro-ocular syndrome. This study investigated whether use of the countermeasure lower-body negative pressure during spaceflight was associated with changes in ocular structure. Objective: To determine whether changes to the optic nerve head and retina during spaceflight can be mitigated by brief in-flight application of 25-mm Hg lower-body negative pressure. Design, Setting, and Participants: In the National Aeronautics and Space Administration's "Fluid Shifts Study," a prospective cohort study, optical coherence tomography scans of the optic nerve head and macula were obtained from US and international crew members before flight, in-flight, and up to 180 days after return to Earth. In-flight scans were obtained both under normal weightless conditions and 10 to 20 minutes into lower-body negative pressure exposure. Preflight and postflight data were collected in the seated, supine, and head-down tilt postures. Crew members completed 6- to 12-month missions that took place on the International Space Station. Data were analyzed from 2016 to 2021. Interventions or Exposures: Spaceflight and lower-body negative pressure. Main Outcomes and Measures: Changes in minimum rim width, optic cup volume, Bruch membrane opening height, peripapillary total retinal thickness, and macular thickness. Results: Mean (SD) flight duration for the 14 crew members (mean [SD] age, 45 [6] years; 11 male crew members [79%]) was 214 (72) days. Ocular changes on flight day 150, as compared with preflight seated, included an increase in minimum rim width (33.8 µm; 95% CI, 27.9-39.7 µm; P < .001), decrease in cup volume (0.038 mm3; 95% CI, 0.030-0.046 mm3; P < .001), posterior displacement of Bruch membrane opening (-9.0 µm; 95% CI, -15.7 to -2.2 µm; P = .009), and decrease in macular thickness (fovea to 500 µm, 5.1 µm; 95% CI, 3.5-6.8 µm; P < .001). Brief exposure to lower-body negative pressure did not affect these parameters. Conclusions and Relevance: Results of this cohort study suggest that peripapillary tissue thickening, decreased cup volume, and mild central macular thinning were associated with long-duration spaceflight. Acute exposure to 25-mm Hg lower-body negative pressure did not alter optic nerve head or retinal morphology, suggesting that longer durations of a fluid shift reversal may be needed to mitigate spaceflight-induced changes and/or other factors are involved.

The Role of Na+/K+-ATPase in the Development of Hyponatrenemia under Conditions of Hypoxic Stress in Patients with SARS-CoV-2 Infection.

We studied laboratory parameters of patients with COVID-19 against the background of chronic pathologies (cardiovascular pathologies, obesity, type 2 diabetes melitus, and cardiovascular pathologies with allergy to statins). A decrease in pH and a shift in the electrolyte balance of blood plasma were revealed in all studied groups and were most pronounced in patients with cardiovascular pathologies with allergy to statin. It was found that low pH promotes destruction of lipid components of the erythrocyte membranes in patients with chronic pathologies, which was seen from a decrease in Na+/K+-ATPase activity and significant hyponatrenemia. In patients with cardiovascular pathologies and allergy to statins, erythrocyte membranes were most sensitive to a decrease in pH, while erythrocyte membranes of obese patients showed the greatest resistance to low pH and oxidative stress.

Characteristics of bioimpedance-determined fluid shifts according to intradialytic blood pressure difference.

This study was designed to identify the fluid spaces that are most changed during ultrafiltration (UF) according to intradialytic blood pressure (BP) difference. BP data were collected five times (before hemodialysis [HD] and 1-4 h of HD). Intradialytic BP difference was calculated as the highest minus lowest of these BP measurements. Intradialytic systolic BP (SBP) difference over 20 mm Hg and diastolic BP (DBP) difference over 10 mm Hg were defined as wide intradialytic SBP difference (SYS-W) and DBP difference (DIA-W), respectively. We measured the various fluid spaces before HD and 1-4 h of HD, and 30 min after HD using a portable, whole-body bioimpedance spectroscopy (BIS). In this study, 85 prevalent patients aged over 18 years with a fixed dry weight (65.38 ± 12.45 years, 54.18% men, 52.50% patients with diabetes), undergoing HD had participated. 1) Mean relative reduction of extracellular water (ECW) was significantly higher in SYS-W than in narrow intradialytic SBP difference (SYS-N) patients from 1 h to 30 min after HD. 2) Mean relative reduction of intracellular water (ICW) was significantly lower in DIA-W than in narrow intradialytic DBP difference (DIA-N) patients from 1 h to 30 min after HD. 3) ECW of patients with SYS-W was significantly lower than that of patients with SYS-N. Patients with SYS-W have the characteristics of fluid shifts in which reduction of ECW was steeper than patients with SYS-N whereas fluid shifts of ICW were lower in patients with DIA-W than patients with DIA-N.

Carbohydrate hastens hypervolemia achieved through ingestion of aqueous sodium solution in resting euhydrated humans.

PURPOSE: Ingesting beverages containing a high concentration of sodium under euhydrated conditions induces hypervolemia. Because carbohydrate can enhance interstitial fluid absorption via the sodium-glucose cotransporter and insulin-dependent renal sodium reabsorption, adding carbohydrate to high-sodium beverages may augment the hypervolemic response. METHODS: To test this hypothesis, we had nine healthy young males ingest 1087 ± 82 mL (16-17 mL per kg body weight) of water or aqueous solution containing 0.7% NaCl, 0.7% NaCl + 6% dextrin, 0.9% NaCl, or 0.9% NaCl + 6% dextrin under euhydrated conditions. Each drink was divided into six equal volumes and ingested at 10-min intervals. During each trial, participants remained resting for 150 min. Measurements were made at baseline and every 30 min thereafter. RESULTS: Plasma osmolality decreased with water ingestion (P ≤ 0.023), which increased urine volume such that there was no elevation in plasma volume from baseline (P ≥ 0.059). The reduction in plasma osmolality did not occur with ingestion of solution containing 0.7% or 0.9% NaCl (P ≥ 0.051). Consequently, urine volume was 176-288 mL smaller than after water ingestion and resulted in plasma volume expansion at 60 min and later times (P ≤ 0.042). In addition, net fluid balance was 211-329 mL greater than after water ingestion (P ≤ 0.028). Adding 6% dextrin to 0.7% or 0.9% NaCl solution resulted in plasma volume expansion within as little as 30 min (P ≤ 0.026), though the magnitudes of the increases in plasma volume were unaffected (P ≥ 0.148). CONCLUSION: Dextrin mediates an earlier hypervolemic response associated with ingestion of high-sodium solution in resting euhydrated young men. (247/250 words).

Discovery of nanoscale sanal flow choking in cardiovascular system: exact prediction of the 3D boundary-layer-blockage factor in nanotubes.

Evidences are escalating on the diverse neurological-disorders and asymptomatic cardiovascular-diseases associated with COVID-19 pandemic due to the Sanal-flow-choking. Herein, we established the proof of the concept of nanoscale Sanal-flow-choking in real-world fluid-flow systems using a closed-form-analytical-model. This mathematical-model is capable of predicting exactly the 3D-boundary-layer-blockage factor of nanoscale diabatic-fluid-flow systems (flow involves the transfer of heat) at the Sanal-flow-choking condition. As the pressure of the diabatic nanofluid and/or non-continuum-flows rises, average-mean-free-path diminishes and thus, the Knudsen-number lowers heading to a zero-slip wall-boundary condition with the compressible-viscous-flow regime in the nanoscale-tubes leading to Sanal-flow-choking due to the sonic-fluid-throat effect. At the Sanal-flow-choking condition the total-to-static pressure ratio (ie., systolic-to-diastolic pressure ratio) is a unique function of the heat-capacity-ratio of the real-world flows. The innovation of the nanoscale Sanal-flow-choking model is established herein through the entropy relation, as it satisfies all the conservation-laws of nature. The physical insight of the boundary-layer-blockage persuaded nanoscale Sanal-flow-choking in diabatic flows presented in this article sheds light on finding solutions to numerous unresolved scientific problems in physical, chemical and biological sciences carried forward over the centuries because the mathematical-model describing the phenomenon of Sanal-flow-choking is a unique scientific-language of the real-world-fluid flows. The 3D-boundary-layer-blockage factors presented herein for various gases are universal-benchmark-data for performing high-fidelity in silico, in vitro and in vivo experiments in nanotubes.

Lymphatic Dysregulation in Patients With Heart Failure: JACC Review Topic of the Week.

The lymphatic system is an integral part of the circulatory system and plays an important role in the volume homeostasis of the human body. The complex anatomy and physiology paired with a lack of simple diagnostic tools to study the lymphatic system have led to an underappreciation of the contribution of the lymphatic system to acute and chronic heart failure (HF). Herein, we discuss the physiological role of the lymphatic system in volume management and the evidence demonstrating the dysregulation of the lymphatic system in HF. Further, we discuss the opportunity to target the lymphatic system in the management of HF and different potential approaches to accessing the lymphatic system.

Response of Pituitary-Thyroid Axis to a Short-Term Shift in Deuterium Content in the Body.

We studied functional changes in rat pituitary-thyroid axis after a short-term shift in deuterium body content. Male Wistar rats consumed deuterium-enriched (500,000 ppm) or deuterium-depleted water (10 ppm) for 24 h. Rats of both experimental groups demonstrated elevated concentration of bound with transport proteins thyroxine and reduced level of thyroid-stimulating hormone in serum. No changes in the rate of thyroxine conversion to triiodothyronine were found. Thus, both the increase and reduction of deuterium body content produced similar changes in the function of the pituitary-thyroid axis with primary affection of the thyroid gland, indicative of its higher sensitivity to shift in deuterium levels.

Pulmonary fluid shifts occur as a result of scuba diving at NASA's Neutral Buoyancy Lab.

Introduction: Pulmonary fluid shifts can occur while scuba diving. Such shifts, generally thought to be rare, may result in a life-threatening phenomenon known as immersion pulmonary edema (IPE). This study aims to better classify the normal physiology of diving using ultrasound (US) to determine if these fluid shifts occur routinely during commercial diving work at the NASA Neutral Buoyancy Laboratory (NBL). Methods: Chest US was performed on commercial divers prospectively pre- and post-dive to evaluate the presence of B-lines in a total of 12 intercostal points on the anterior, posterior, and lateral chest wall. The number of B-lines at each anatomic site was recorded and scored by two independent reviewers. An increase in the number of B-lines post-dive was considered a positive result. Results: There were 67 exposures; 39 (58%) had an increase of one or more B-lines post dive; 64% of the female exposures and 57% of the male exposures were positive for B-lines post-dive, suggesting no difference across gender (Fisher's exact; p = 0.763). After the dive, all divers remained asymptomatic. Conclusion: From our results, fluid shifts can be viewed as a normal, transient, and physiologic process in commercial divers. This correlation can be compared to the formation of low-grade venous gas emboli (VGE) from decompression that does not result in decompression sickness. Further study of US B-lines in symptomatic divers may define the utility of field US in the diagnosis and management of IPE, and help identify associated risk factors.

Acute heart failure.

Acute heart failure (AHF) is a syndrome defined as the new onset (de novo heart failure (HF)) or worsening (acutely decompensated heart failure (ADHF)) of symptoms and signs of HF, mostly related to systemic congestion. In the presence of an underlying structural or functional cardiac dysfunction (whether chronic in ADHF or undiagnosed in de novo HF), one or more precipitating factors can induce AHF, although sometimes de novo HF can result directly from the onset of a new cardiac dysfunction, most frequently an acute coronary syndrome. Despite leading to similar clinical presentations, the underlying cardiac disease and precipitating factors may vary greatly and, therefore, the pathophysiology of AHF is highly heterogeneous. Left ventricular diastolic or systolic dysfunction results in increased preload and afterload, which in turn lead to pulmonary congestion. Fluid retention and redistribution result in systemic congestion, eventually causing organ dysfunction due to hypoperfusion. Current treatment of AHF is mostly symptomatic, centred on decongestive drugs, at best tailored according to the initial haemodynamic status with little regard to the underlying pathophysiological particularities. As a consequence, AHF is still associated with high mortality and hospital readmission rates. There is an unmet need for increased individualization of in-hospital management, including treatments targeting the causative factors, and continuation of treatment after hospital discharge to improve long-term outcomes.

Usefulness of raw bioelectrical impedance parameters in tracking fluid shifts in judo athletes.

Bioelectrical impedance (BI) has been widely used but clarification about the behaviour of raw BI measurements under specific athletic conditions is required. Thus, we determined the usefulness of raw BI measures in tracking body fluids changes during the preparation period prior to competition in elite Judo athletes. At baseline (weight stability), 27 male athletes were evaluated (23.2 ± 2.8y) and again 1-3 days before competition (∼1-2 months apart). Athletes were free to gain/lost weight based upon specific competition needs. Using dilution techniques (deuterium and bromide), total-body water (TBW) and extracellular water were estimated, and intracellular water calculated as TBW minus extracellular water. Body fluid distribution was determined as Extra-to-/Intracellular water (E/I). Fat and fat-free mass (FFM) was assessed by dual-energy x-ray absorptiometry. Resistance, reactance, and phase angle (PhA) were obtained from bioelectrical impedance spectroscopy (50-kHz frequency). No differences in raw BI measures were observed between athletes that lost (N = 17) or gain weight (N = 10), except for fat, FFM, extracellular water, and EI (p < 0.05). After adjusting for FFM and height, resistance explained TBW (ß = -0.047, p = 0.002) and extracelular water (ß = -0.025, p = 0.001). Reactance explained ECW (ß = -0.098, p = 0.004) and EI (ß = -0.004, p = 0.006), while PhA predicted TBW (ß = 1.609, p = 0.047), ICW (ß = 1.899, p = 0.001) and EI (ß = -0.056, p = 0.001). Regardless of body composition changes, athletes who increase reactance and resistance reduced extracellular water and body fluids while those who raised PhA increased intracellular water. Judo athletes who reduced weight, decreased FFM but cellular health was not compromised, as PhA remained stable and, consequently, cell hydration.

Postural preinspiratory cortical activity, genioglossus activity and fluid shift in awake obstructive sleep apnoea patients.

NEW FINDING: What is the central question of this study? Transition to supine posture induces an inspiratory load associated with cortical activation in awake healthy subjects. Some obstructive sleep apnoea patients exhibit this cortical activity in the sitting position contributing to the arousal-dependent compensation of their upper airway abnormalities. Does a transition to the supine posture in awake obstructive sleep apnoea patients increase this cortical activity? What is the main finding and its importance? The transition to supine posture induces a reduction in the cortical activity despite evidence of an increase in genioglossus activity, suggesting that genioglossus activation is not driven by cortical activity. ABSTRACT: The anatomy and mechanical properties of the upper airway (UA) depend on posture. Lying in a supine position causes cephalad fluid shift to the neck, thus narrowing the UA and predisposing the individual to obstructive sleep apnoea (OSA). Increased UA dilator muscle activity during wakefulness prevents the UA collapse but the underlying mechanism has not yet been elucidated. In the sitting position during wakefulness, some OSA patients exhibit preinspiratory cortical activity (preinspiratory potential, PIP) probably related to UA abnormalities. The aim of this study was to investigate changes in the preinspiratory cortical activity and UA dilator muscle in OSA patients during postural challenge. An electroencephalogram was used to detect PIP, and the genioglossus electromyographic activity and ventilation were analysed in 17 awake, male OSA patients while they were sitting, just after lying down, and then in response to leg positive pressure to enhance cephalad fluid shift. The prevalence of PIP decreased from 53% (sitting) to 12% (supine) (P = 0.002) in association with increased genioglossus activity (tonic from median (25th, 75th centiles) 2.3 (1.8, 2.8)% to 3.6 (1.7, 5.0)% of voluntary deglutition, P = 0.019; phasic from 2.3 (1.9, 2.8)% to 3.7 (2.0, 6.1)%, P = 0.024), and with increased transcutaneous carbon dioxide pressure (from 43.0 (42.4, 44.2) to 44.6 (43.5, 45.2) mmHg). No change was observed during leg-positive-pressure application. Moving from the sitting position to the supine position reduces respiratory-related premotor cortical activity in awake OSA patients. The concomitant increase in genioglossus activity, therefore, is not driven by cortical respiratory activity.

Mobile Lower Body Negative Pressure Suit as an Integrative Countermeasure for Spaceflight.

BACKGROUND: Persistent headward fluid shift and mechanical unloading cause neuro-ocular, cardiovascular, and musculoskeletal deconditioning during long-term spaceflight. Lower body negative pressure (LBNP) reintroduces footward fluid shift and mechanical loading.METHODS: We designed, built, and tested a wearable, mobile, and flexible LBNP device (GravitySuit) consisting of pressurized trousers with built-in shoes to support ground reaction forces (GRF) and a thoracic vest to distribute load to the entire axial length of the body. In eight healthy subjects we recorded GRF under the feet and over the shoulders (Tekscan) while assessing cardiovascular response (Nexfin) and footward fluid shift from internal jugular venous cross-sectional area (IJVa) using ultrasound (Terason).RESULTS: Relative to normal bodyweight (BW) when standing upright, increments of 10 mmHg LBNP from 0 to 40 mmHg while supine induced axial loading corresponding to 0%, 13 ± 3%, 41 ± 5%, 75 ± 11%, and 125 ± 22% BW, respectively. Furthermore, LBNP reduced IJVa from 1.12 ± 0.3 cm² to 0.67 ± 0.2, 0.50 ± 0.1, 0.35 ± 0.1, and 0.31 ± 0.1 cm², respectively. LBNP of 30 and 40 mmHg reduced cardiac stroke volume and increased heart rate while cardiac output and mean arterial pressure were unaffected. During 2 h of supine rest at 20 mmHg LBNP, temperature and humidity inside the suit were unchanged (23 ± 1°C; 47 ± 3%, respectively).DISCUSSION: The flexible GravitySuit at 20 mmHg LBNP comfortably induced mechanical loading and desired fluid displacement while maintaining the mobility of hips and knee joints. The GravitySuit may provide a feasible method to apply low-level, long-term LBNP without interfering with daily activity during spaceflight to provide an integrative countermeasure.Petersen LG, Hargens A, Bird EM, Ashari N, Saalfeld J, Petersen JCG. Mobile lower body negative pressure suit as an integrative countermeasure for spaceflight. Aerosp Med Hum Perform. 2019; 90(12):993-999.

Mechanisms for hemodynamic instability related to renal replacement therapy: a narrative review.

Hemodynamic instability related to renal replacement therapy (HIRRT) is a frequent complication of all renal replacement therapy (RRT) modalities commonly used in the intensive care unit. HIRRT is associated with increased mortality and may impair kidney recovery. Our current understanding of the physiologic basis for HIRRT comes primarily from studies of end-stage kidney disease patients on maintenance hemodialysis in whom HIRRT is referred to as 'intradialytic hypotension'. Nonetheless, there are many studies that provide additional insights into the underlying mechanisms for HIRRT specifically in critically ill patients. In particular, recent evidence challenges the notion that HIRRT is almost entirely related to excessive ultrafiltration. Although excessive ultrafiltration is a key mechanism, multiple other RRT-related mechanisms may precipitate HIRRT and this could have implications for how HIRRT should be managed (e.g., the appropriate response might not always be to reduce ultrafiltration, particularly in the context of significant fluid overload). This review briefly summarizes the incidence and adverse effects of HIRRT and reviews what is currently known regarding the mechanisms underpinning it. This includes consideration of the evidence that exists for various RRT-related interventions to prevent or limit HIRRT. An enhanced understanding of the mechanisms that underlie HIRRT, beyond just excessive ultrafiltration, may lead to more effective RRT-related interventions to mitigate its occurrence and consequences.

Temporal shifts in fluid in pulmonary hypertension with and without sleep apnea.

Overnight extracellular rostral fluid shifts have been shown to be of importance in patients with fluid-retaining states and are associated with a higher prevalence of sleep apnea. Pulmonary hypertension is frequently associated with right ventricular dysfunction and progressive right ventricular failure, and an increased prevalence of sleep apnea has been described. In light of the importance of fluid shifts in the pathophysiology of sleep apnea, we aimed to explore temporal fluid shifts in patients with pulmonary hypertension with and without sleep apnea. Patients with pulmonary hypertension (WHO Group 1 or 4) had overnight extracellular rostral fluid shift assessment before and a minimum of 3 months after initiation of pulmonary hypertension-specific therapy. Fluid shift measurements of extracellular leg, abdominal, thoracic and neck fluid volumes were performed simultaneously. Twenty-nine patients with pulmonary hypertension (age 55 ± 16 years, 69% female) participated. Sleep apnea was diagnosed in 15 subjects (apnea-hypopnea index 14 [8-27] per hr). There were no significant differences in baseline or overnight leg extracellular rostral fluid, abdominal extracellular rostral fluid, thoracic extracellular rostral fluid or neck extracellular rostral fluid between those with and without sleep apnea. There was a significant inverse correlation between the sleep apnea severity and the overnight change in leg extracellular rostral fluid (r = -0.375, p = 0.049). There were no significant differences detected in overnight extracellular rostral fluid shifts from baseline to follow-up. Treatment-naïve patients with pulmonary hypertension both with and without sleep apnea demonstrate overnight extracellular rostral fluid shifts from the legs into the thorax and neck. Pulmonary hypertension-specific treatment, while significantly improving cardiac haemodynamics, had little impact on nocturnal extracellular rostral fluid shifts or the presence of sleep apnea.

Postural respiratory-related cortical activation and rostral fluid shift in awake healthy humans.

NEW FINDINGS: What is the central question of this study? Moving to supine induces upper airway modifications and a fluid shift to the neck, which represent inspiratory load that predisposes to upper airway collapse. Is there cortical participation in the response to the load induced by transition to a supine posture in awake healthy subjects? What is the main finding and its importance? Moving to supine induces transient cortical activation in awake healthy subjects, with greater fluid shift, supporting possible cortical participation in the response to upper airway load induced by transition to a supine posture. Our findings open new perspectives in the understanding of the pathogenesis of obstructive sleep apnoea. ABSTRACT: Moving from sitting upright to lying supine causes anatomical modifications and a fluid shift to the neck, which represent inspiratory loads that predispose to upper airway collapse. The pre-inspiratory potential (PIP) corresponds to the cortical activity observed during inspiratory load. In the sitting position during wakefulness, some obstructive sleep apnoea patients exhibit PIP, probably in relationship to upper airway abnormalities. The aim of this study was to investigate whether moving to the supine position induces respiratory-related cortical activation (PIP) in awake healthy subjects. The ECG was analysed to detect PIP, and EMG activity of the genioglossus muscle and ventilation were measured in the sitting position, immediately after moving to the supine position, and during application of leg positive pressure in the supine position to promote fluid shift, which was measured by bioelectrical impedance. Twenty-four subjects were included. From sitting to lying, PIP prevalence increased from 1/24 to 11/24 (P = 0.002), and ventilation decreased with no change in genioglossus activity. The fluid shift from sitting to supine was higher in the subjects exhibiting PIP while supine compared with the subjects without PIP [median (25th; 75th centiles) 440 (430; 520) versus 320 (275; 385) ml, P = 0.018], without any other differences. From before to during leg positive pressure, PIP disappeared (P = 0.006). These results indicate that moving from sitting to lying induces transient respiratory-related cortical activity in awake healthy subjects with greater fluid shift, supporting possible cortical participation in the response to upper airway loading induced by moving from sitting upright to lying supine. This study offers new perspectives in the understanding of obstructive sleep apnoea pathogenesis.

Effect of Trendelenburg position and lower-body positive pressure on neck fluid distribution.

Fluid that shifts out of the legs and into the neck when supine can contribute to upper-airway narrowing. The present study investigates the relative contributions of vascular and extravascular fluid to the total accumulation of neck fluid volume (NFV). In 22 healthy awake participants (8 women), aged 42 ± 9 yr, we measured NFV with bioelectrical impedance, internal jugular vein volume (IJVV) with ultrasound, and extravascular NFV (NFVEV) as the difference between NFV and IJVV. Participants were randomly allocated to control and intervention, both of which were conducted on the same day. Measurements were made at baseline and every 5 min thereafter during control and intervention. During intervention, participants received 40 mmHg lower-body positive pressure (LBPP) when supine, followed by LBPP plus 10° Trendelenburg position, then LBPP when supine again, followed by recovery. During control, participants lay supine for equal time. LBPP and LBPP plus Trendelenburg position both increased NFV from baseline compared with control (P < 0.001), with significant contributions from IJVV (P < 0.001). Returning to supine with LBPP, IJVV returned to baseline, but NFV remained elevated because of accumulation of NFVEV. These findings suggest that contributions of IJVV to NFV are immediate but transient, whereas sustained elevation in NFV when supine is likely a result of NFVEV. These findings add new insights into the mechanism by which fluid accumulates in the neck by rostral fluid shift. NEW & NOTEWORTHY This study demonstrates that lying supine for 30 min as well as increased fluid shift out of the legs to simulate nocturnal rostral fluid shift causes fluid to accumulate mainly in the extravascular space of the neck rather than in the internal jugular veins. Therefore, in subjects without fluid-retaining states, extravascular neck fluid accumulation overnight might play a more significant role in the pathophysiology of upper-airway narrowing than intravascular fluid accumulation.

Spaceflight-Associated Brain White Matter Microstructural Changes and Intracranial Fluid Redistribution.

Importance: Spaceflight results in transient balance declines and brain morphologic changes; to our knowledge, the effect on brain white matter as measured by diffusion magnetic resonance imaging (dMRI), after correcting for extracellular fluid shifts, has not been examined. Objective: To map spaceflight-induced intracranial extracellular free water (FW) shifts and to evaluate changes in brain white matter diffusion measures in astronauts. Design, Setting and Participants: We performed retrospective, longitudinal analyses on dMRI data collected between 2010 and 2015. Of the 26 astronauts' dMRI scans released by the National Aeronautics and Space Administration Lifetime Surveillance of Astronaut Health, 15 had both preflight and postflight dMRI scans and were included in the final analyses. Data were analyzed between 2015 and 2018. Interventions or Exposures: Seven astronauts completed a space shuttle mission (≤30 days) and 8 completed a long-duration International Space Station mission (≤200 days). Main Outcomes and Measures: The dMRI scans were acquired for clinical monitoring; in this retrospective analysis, we analyzed brain FW and white matter diffusion metrics corrected for FW. We also obtained scores from computerized dynamic posturography tests of balance to assess brain-behavior associations. Results: Of the 15 astronauts included, the median (SD) age was 47.2 (1.5) years; 12 were men, and 3 were women. We found a significant, widespread increase in FW volume in the frontal, temporal, and occipital lobes from before spaceflight to after spaceflight. There was also a significant decrease in FW in the posterior aspect of the vertex. All FW changes were significant and ranged from approximately 2.5% to 4.0% across brain regions. We observed white matter changes in the right superior and inferior longitudinal fasciculi, the corticospinal tract, and cerebellar peduncles. All white matter changes were significant and ranged from approximately 0.75% to 1.25%. Spaceflight mission duration was associated with cerebellar white matter change, and white matter changes in the superior longitudinal fasciculus were associated with the balance changes seen in the astronauts from before spaceflight to after spaceflight. Conclusions and Relevance: Free water redistribution with spaceflight likely reflects headward fluid shifts occurring in microgravity as well as an upward shift of the brain within the skull. White matter changes were of a greater magnitude than those typically seen during the same period with healthy aging. Future, prospective assessments are required to better understand the recovery time and behavioral consequences of these brain changes.

Direct visualizations of air flow in the human upper airway using in-vitro models.

A better understanding of airflow characteristics in the upper airway (UA) is crucial in investigating obstructive sleep apnea (OSA), particle sedimentation, drug delivery, and many biomedical problems. Direct visualization of air flow patterns in in-vitro models with realistic anatomical structures is a big challenge. In this study, we constructed unique half-side transparent physical models of normal UA based on realistic anatomical structures. A smoke-wire method was developed to visualize the air flow in UA models directly. The results revealed that the airflow through the pharynx was laminar but not turbulent under normal inspiration, which suggested that compared with turbulent models, a laminar model should be more suitable in numerical simulations. The flow predicted numerically using the laminar model was consistent with the observations in the physical models. The comparison of the velocity fields predicted numerically using the half-side and complete models confirmed that it was reasonable to investigate the flow behaviors in UA using the half-side model. Using the laminar model, we simulated the flow and evaluated the effects of UA narrowing caused by rostral fluid shift on pharyngeal resistance. The results suggested that fluid shift could play an important role in the formation of hypopnea or OSA during sleep.