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.

Short-Term Segmental Bioimpedance Alterations During 6° Head-Down Tilt.

As missions in space increase in duration and distance from Earth it is critical to understand the impact that exposure to microgravity has on the health and potential performance of crews. Segmental bioimpedance measurements can track resistances changes in tissues that result from fluid redistribution and could be a tool for continuous fluid shift monitoring in microgravity. In this work, the range of segmental (legs, arms, torso, and neck) 10 kHz and 100 kHz resistances and their relative changes during 4 hours of 6° head down tilt are reported as well as the observed resistance differences between left/right body segments throughout the protocol.

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.

Overnight Rostral Fluid Shifts Exacerbate Obstructive Sleep Apnea After Stroke.

Background and Purpose: Overnight shifts of fluid from lower to upper compartments exacerbate obstructive sleep apnea (OSA) in some OSA populations. Given the high prevalence of OSA after stroke, decreased mobility and use of IV fluids among hospitalized patients with stroke, and improvement in OSA in the months after stroke, we hypothesized that overnight fluid shifts occur and are associated with OSA among patients with subacute ischemic stroke. Methods: Within a population-based project, we performed overnight sleep apnea tests (ApneaLink Plus) during ischemic stroke hospitalizations. Before sleep that evening, and the following morning before rising from bed, we assessed neck and calf circumference, and leg fluid volume (bioimpedance spectroscopy). The average per subject overnight change in the 3 fluid shift measurements was calculated and compared with zero. Linear regression was used to test the crude association between each of the 3 fluid shift measurements and the respiratory event index (REI). Results: Among the 292 participants, mean REI was 24 (SD=18). Within individuals, calf circumference decreased on average by 0.66 cm (SD=0.75 cm, P<0.001), leg fluid volume decreased by a mean of 135.6 mL (SD=132.8 mL, P<0.001), and neck circumference increased by 0.20 cm (SD=1.71 cm, P=0.07). In men, when the overnight change of calf circumference was negative, an interquartile range (0.8 cm) decrease in calf circumference overnight was significantly associated with a 25.1% increase in REI (P=0.02); the association was not significant in women. The relationship between overnight change in leg fluid volume and REI was U shaped. Conclusions: This population-based, multicenter, cross-sectional study showed that in hospitalized patients with ischemic stroke, nocturnal rostral fluid shifts occurred, and 2 of the 3 measures were associated with greater OSA severity. Interventions that limit overnight fluid shifts should be tested as potential treatments for OSA among patients with subacute ischemic stroke.

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.

Turbulence Intensity as an Indicator for Ischemic Stroke in the Carotid Web.

OBJECTIVE: Carotid web (CaW) is reported as one of the causes of cryptogenic strokes. However, its pathophysiology is not known, which makes clinicians debate CaW treatment. The current study presents the mechanism of ischemic stroke in CaW and finds a potential indicator for ischemic stroke in CaW. METHODS: Computational fluid dynamics (CFD) was applied to computer-aided artificial human CaW models to investigate the correlation between stenosis rate and CaW angle. The CFD results were compared with stroke or symptomatic CaW including adequate reported images for anatomic analysis of the stenosis rate and CaW angle. RESULTS: The CFD result of the CaW models shows that the velocity decreases and the turbulence generation of blood flow increases in the area under CaW (AuCaW). In AuCaW, turbulence intensity (TI) is high in the high stenosis rate and small angle conditions. Moreover, TI remained high in the AuCaW throughout the cardiac cycles. The analysis of 67 anatomic figures appeared in 36 articles merged with CFD results, and a CaW scoring system was introduced for clinicians to determine patients with CaW with a high risk of ischemic stroke. CONCLUSIONS: This study is believed to be the first to apply TI to CaW. Because most ischemic strokes in CaW occurred at a high stenosis rate and small angle, TI may be used as a potential indicator of ischemic stroke in CaW. Furthermore, TI is easily used in the daily clinical field by applying CaW scores.

Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial.

BACKGROUNDS/AIM: Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD). METHODS: The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. RESULTS: In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by - 2.23% (95% CI - 5.72 to 1.25) at week 4, - 8.07% (- 12.76 to - 3.37) at week 12, and - 5.60% (- 9.87 to - 1.32) at week 24; eEV by - 70.3 mL (95% CI - 136.8 to - 3.8) at week 4, - 135.9 mL (- 209.6 to - 62.3) at week 12, and - 144.4 mL (- 226.3 to - 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV. CONCLUSIONS: Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502.

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.

Mechanical countermeasures to headward fluid shifts.

Head-to-foot gravitationally induced hydrostatic pressure gradients in the upright posture on Earth are absent in weightlessness. This results in a relative headward fluid shift in the vascular and cerebrospinal fluid compartments and may underlie multiple physiological consequences of spaceflight, including the spaceflight-associated neuro-ocular syndrome. Here, we tested three mechanical countermeasures [lower body negative pressure (LBNP), venoconstrictive thigh cuffs (VTC), and impedance threshold device (ITD) resistive inspiratory breathing] individually and in combination to reduce a posture-induced headward fluid shift as a ground-based spaceflight analog. Ten healthy subjects (5 male) underwent baseline measures (seated and supine postures) followed by countermeasure exposure in the supine posture. Noninvasive measurements included ultrasound [internal jugular veins (IJV) cross-sectional area, cardiac stroke volume, optic nerve sheath diameter, noninvasive IJV pressure], transient evoked otoacoustic emissions (OAE; intracranial pressure index), intraocular pressure, choroidal thickness from optical coherence tomography imaging, and brachial blood pressure. Compared with the supine posture, IJV area decreased 48% with application of LBNP [mean ratio: 0.52, 95% confidence interval (CI): 0.44-0.60, P < 0.001], 31% with VTC (mean ratio: 0.69, 95% CI: 0.55-0.87, P < 0.001), and 56% with ITD (mean ratio: 0.44, 95% CI: 0.12-1.70, P = 0.46), measured at end-inspiration. LBNP was the only individual countermeasure to decrease the OAE phase angle (Δ -12.9 degrees, 95% CI: -25 to -0.9, P = 0.027), and use of combined countermeasures did not result in greater effects. Thus, LBNP, and to a lesser extent VTC and ITD, represents promising headward fluid shift countermeasures but will require future testing in analog and spaceflight environments.NEW & NOTEWORTHY As a weightlessness-induced headward fluid shift is hypothesized to be a primary factor underlying several physiological consequences of spaceflight, countermeasures aimed at reversing the fluid shift will likely be crucial during exploration-class spaceflight missions. Here, we tested three mechanical countermeasures individually and in various combinations to reduce a posture-induced headward fluid shift as a ground-based spaceflight analog.

Exercise-induced fluid shifts are distinct to exercise mode and intensity: a comparison of blood flow-restricted and free-flow resistance exercise.

MRI can provide fundamental tools in decoding physiological stressors stimulated by training paradigms. Acute physiological changes induced by three diverse exercise protocols known to elicit similar levels of muscle hypertrophy were evaluated using muscle functional magnetic resonance imaging (mfMRI). The study was a cross-over study with participants (n = 10) performing three acute unilateral knee extensor exercise protocols to failure and a work matched control exercise protocol. Participants were scanned after each exercise protocol; 70% 1 repetition maximum (RM) (FF70); 20% 1RM (FF20); 20% 1RM with blood flow restriction (BFR20); free-flow (FF) control work matched to BFR20 (FF20WM). Post exercise mfMRI scans were used to obtain interleaved measures of muscle R2 (indicator of edema), R2' (indicator of deoxyhemoglobin), muscle cross sectional area (CSA) blood flow, and diffusion. Both BFR20 and FF20 exercise resulted in a larger acute decrease in R2, decrease in R2', and expansion of the extracellular compartment with slower rates of recovery. BFR20 caused greater acute increases in muscle CSA than FF20WM and FF70. Only BFR20 caused acute increases in intracellular volume. Postexercise muscle blood flow was higher after FF70 and FF20 exercise than BFR20. Acute changes in mean diffusivity were similar across all exercise protocols. This study was able to differentiate the acute physiological responses between anabolic exercise protocols. Low-load exercise protocols, known to have relatively higher energy contributions from glycolysis at task failure, elicited a higher mfMRI response. Noninvasive mfMRI represents a promising tool for decoding mechanisms of anabolic adaptation in muscle.NEW & NOTEWORTHY Using muscle functional MRI (mfMRI), this study was able to differentiate the acute physiological responses following three established hypertrophic resistance exercise strategies. Low-load exercise protocols performed to failure, with or without blood flow restriction, resulted in larger changes in R2 (i.e. greater T2-shifts) with a slow rate of return to baseline indicative of myocellular fluid shifts. These data were cross evaluated with interleaved measures of macrovascular blood flow, water diffusion, muscle cross sectional area (i.e. acute macroscopic muscle swelling), and intracellular water fraction measured using MRI.

Hemodialysis Emergencies: Core Curriculum 2021.

Since maintenance hemodialysis (HD) first became available in the United States in 1962, there has been tremendous growth in the population of patients with kidney failure. HD has become a routine treatment carried out in outpatient clinics, hospitals, nursing facilities, and in patients' homes. Although it is a complex procedure, HD is quite safe. Serious complications are uncommon due to the use of modern HD machines and water treatment systems as well as the development of strict protocols to monitor various aspects of the HD treatment. The practicing nephrologist must be knowledgeable about life-threatening complications that can occur during HD and be able to recognize, manage, and prevent them. This installment in the AJKD Core Curriculum in Nephrology reviews the pathogenesis, management, and prevention of 9 HD emergencies. The HD emergencies covered include dialyzer reactions, dialysis disequilibrium syndrome, uremic/dialysis-associated pericarditis, air embolism, venous needle dislodgement, vascular access hemorrhage, hemolysis, dialysis water contamination, and arrhythmia episodes.

Effect of compression stockings on overnight rostral fluid shift and obstructive sleep apnea: A meta-analysis.

OBJECTIVE: The overnight rostral fluid shift from the lower limbs is one of the causes of obstructive sleep apnea (OSA). Compression stockings (CS) prevent lower limb fluid retention and have been reported to decrease nighttime fluid shift. The aim of this study is to evaluate the effect of CS on fluid shift and the severity of OSA. METHODS: A systematic literature search was performed in the PubMed, EMBASE and Cochrane Library databases. The data were analyzed using Comprehensive Meta-Analysis software (Version 3; Biostat, Englewood, NJ). Studies evaluating the effect of CS on the overnight fluid shift and OSA severity were included in the analysis. RESULTS: A total of 4 studies were included in this meta-analysis. The pooled analysis showed that the apnea-hypopnea index (AHI) of the overall study group was significantly lower after using CS (SMD, -1.08; 95% CI, -1.49 to -0.67). Decreases in the AHI were also observed in the normal fluid status (SMD, -1.05; 95% CI, -1.73 to -0.37) and fluid overload status (SMD, -1.17; 95% CI, -1.76 to -0.58) populations. The overall study group had significant decreases in overnight changes in neck circumference (SMD, -1.05; 95% CI, -2.06 to -0.03) and leg fluid volume (SMD, -1.14; 95% CI, -1.88 to -0.41) after using CS. However, no significant differences in overnight changes in neck circumference and leg fluid volume were observed in normal fluid status patients. CONCLUSION: CS may help decrease overnight fluid shift and could be a treatment option for OSA.

Point-of-Care Lung Ultrasound Pattern in Healthy Parturients: Prevalence of Pulmonary Interstitial Syndrome Following Vaginal Delivery, Elective and Unplanned Intrapartum Cesarean Delivery.

BACKGROUND: Pregnancy-related cardiovascular physiologic changes increase the likelihood of pulmonary edema, with the risk of fluid extravasating into the pulmonary interstitium being potentially at a maximum during the early postpartum period. Data on the impact of labor and peripartum hemodynamic strain on lung ultrasound (LUS) are limited, and the prevalence of subclinical pulmonary interstitial syndrome in peripartum women is poorly described. The primary aim of this exploratory study was to estimate the prevalence of pulmonary interstitial syndrome in healthy term parturients undergoing vaginal (VD), elective (eCD), and unplanned intrapartum cesarean deliveries (uCD). Secondary aims were to estimate the prevalence of positive lung regions (≥3 B-lines on LUS per region) and to assess the associations between positive lung regions and possible contributing factors. METHODS: In this prospective observational cohort study, healthy women at term undergoing VD, eCD, or uCD were enrolled. Following international consensus recommendations, a LUS examination was performed within 4 hours after delivery applying an 8-region technique. Pulmonary interstitial syndrome was defined by the presence of 2 or more positive lung regions per hemithorax. Ultrasound studies were reviewed by 2 blinded reviewers and assessed for interobserver reliability. RESULTS: Seventy-five women were assessed (n = 25 per group). No pulmonary interstitial syndrome was found in the VD and eCD groups (each 0 of 25; 0%, 95% confidence interval [CI], 0-13.7). Pulmonary interstitial syndrome was found in 2 of 25 (8%, 95% CI, 1-26) women undergoing an uCD (P = .490 for VD versus uCD and P = .490 for eCD versus uCD). In 1 woman, this correlated clinically with the development of pulmonary edema. One or more positive lung regions were present in 5 of 25 (20%), 6 of 25 (24%), and 11 of 25 (44%) parturients following VD, eCD, and uCD, respectively (P = .136). Positive lung regions were predominantly found in lateral lung regions. The number of positive lung regions showed a weak correlation with patient age (r = 0.25, 95% CI, 0.05-0.47; P = .033). No significant association was found between LUS pattern and parity, duration of labor, labor augmentation, labor induction, estimated total intravenous fluid intake, or net intravenous fluid intake. CONCLUSIONS: Although many focal areas of increased extravascular lung water (20%-44% prevalence) can be identified on LUS, the overall prevalence of pulmonary interstitial syndrome was 2.7% (2 of 75; 95% CI, 0.3-9.3) among healthy term parturients soon after delivery. Focal areas of positive lung water regions were weakly correlated with maternal age.

Disparate volumetric fluid shifts across cerebral tissue compartments with two different anesthetics.

BACKGROUND: Large differences in glymphatic system transport-similar in magnitude to those of the sleep/wake cycle-have been observed during anesthesia with dexmedetomidine supplemented with low dose isoflurane (DEXM-I) in comparison to isoflurane (ISO). However, the biophysical and bioenergetic tissue status underlying glymphatic transport differences between anesthetics remains undefined. To further understand biophysical characteristics underlying these differences we investigated volume status across cerebral tissue compartments, water diffusivity, and T2* values in rats anesthetized with DEXM-I in comparison to ISO. METHODS: Using a crossover study design, a group of 12 Sprague Dawley female rats underwent repetitive magnetic resonance imaging (MRI) under ISO and DEXM-I. Physiological parameters were continuously measured. MRI included a proton density weighted (PDW) scan to investigate cerebrospinal fluid (CSF) and parenchymal volumetric changes, a multigradient echo scan (MGE) to calculate T2* maps as a measure of 'bioenergetics', and a diffusion scan to quantify the apparent diffusion coefficient (ADC). RESULTS: The heart rate was lower with DEXM-I in comparison to ISO, but all other physiological variables were similar across scans and groups. The PDW images revealed a 1% parenchymal volume increase with ISO compared to DEXM-I comprising multiple focal tissue areas scattered across the forebrain. In contrast, with DEXM-I the CSF compartment was enlarged by ~ 6% in comparison to ISO at the level of the basal cisterns and peri-arterial conduits which are main CSF influx routes for glymphatic transport. The T2* maps showed brain-wide increases in T2* in ISO compared to DEXM-I rats. Diffusion-weighted images yielded no significant differences in ADCs across the two anesthesia groups. CONCLUSIONS: We demonstrated CSF volume expansion with DEXM-I (in comparison to ISO) and parenchymal (GM) expansion with ISO (in comparison to DEXM-I), which may explain the differences in glymphatic transport. The T2* changes in ISO are suggestive of an increased bioenergetic state associated with excess cellular firing/bursting when compared to DEXM-I.

Quantification of body fluid compartmentalization by combined time-domain nuclear magnetic resonance and bioimpedance spectroscopy.

The measurement of fluid compartmentalization, or the distribution of fluid volume between extracellular (ECF) and intracellular (ICF) spaces, historically requires complicated, burdensome, and often terminal methodologies that do not permit repeated or longitudinal experiments. New technologies including time-domain nuclear magnetic resonance (TD-NMR)-based methods allow for highly accurate measurements of total body water (TBW) within minutes in a noninvasive manner, but do not permit dissection of ECF versus ICF reservoirs. In contrast, methods such as bioimpedance spectroscopy (BIS) allow dissection of ECF versus ICF reservoirs but are hampered by dependence on many nuanced details in data collection that undermine confidence in experimental results. Here, we present a novel combinatorial use of these two technologies (NMR/BIS) to improve the accuracy of BIS-based assessments of ECF and ICF, while maintaining the advantages of these minimally invasive methods. Briefly, mice undergo TD-NMR and BIS-based measures, and then fat masses as derived by TD-NMR are used to correct BIS outputs. Mice of the C57BL/6J background were studied using NMR/BIS methods to assess the effects of acute furosemide injection and diet-induced obesity on fluid compartmentalization, and to examine the influence of sex, body mass and composition, and diet on TBW, ECF, and ICF. We discovered that in mice, sex and body size/composition have substantial and interactive effects on fluid compartmentalization. We propose that the combinatorial use of NMR/BIS methods will enable a revisioning of the types of longitudinal, kinetic studies that can be performed to understand the impact of various interventions on body fluid homeostasis.

Syndecan-1 and Glypican-1 Knockout Alters Body Water Balance and Urine Response to Fluid Challenge in Mice.

Syndecan-1 (Sdc-1) and glypican-1 (Gpc-1) are 2 important proteoglycans found in the glycocalyx and believed to govern transvascular distribution of fluid and protein. In this translational study, we assessed Sdc-1 and Gpc-1 knockout (KO) on whole body water balance after an intravenous volume challenge. Sdc-1 and Gpc-1 KO mice had higher starting blood water content versus strain-matched controls. Sdc-1 KO mice exhibited a significantly higher diuretic response (87%; p < 0.05), higher excreted volume/infusion volume ratio (p < 0.01), higher extravascular/infused ratio, and greater tissue water concentration (60 vs. 52%). Collectively, these suggest differences in kidney response and greater fluid efflux from peripheral vessels. The CD1 strain and Gpc-1 KO had a 2-3-fold larger urine output relative to C57 strain, but Gpc-1 KO reduced the excreted/infused ratio relative to controls (p < 0.01) and they maintained plasma dilution longer. Thus, genetic KO of Sdc-1 and Gpc-1 resulted in markedly different phenotypes. This work establishes the feasibility of performing fluid balance studies in mice.