Noninvasive Point of Care Device for Assessing Cardiac Response to Acute Volume Changes.

Purpose: The change in the amplitude of a peripheral pulse in response to a Valsalva maneuver has diagnostic utility for assessing volume status at the bedside. We have developed a device to automatically quantify the Valsalva pulse response (VPR) to a standardized Valsalva maneuver that the device guides a user to perform. In this study, we sought to determine whether VPR by the device, Indicor, is sensitive enough to detect the acute increase in central pressure and volume load that occurs with a passive leg raise (PLR) in healthy volunteers. Methods: Healthy volunteers were tested semirecumbently at 45 degrees, then again after being leaned back on a pivoted wedge with legs raised at 45 degrees and torso and head flat, and then again in the semirecumbent position. The device recorded a finger photoplethysmography (PPG) signal during a 10-second expiratory effort of 20 mmHg as guided by the device. VPR was automatically calculated as the ratio of the end-Valsalva pulse amplitude to the baseline pulse amplitude. Results: In the 30 participants who completed testing, VPR increased from baseline to PLR in every participant, from 0.34 ± 0.13 to 0.60 ± 0.14 (p < 0.0001). Back upright, VPR decreased back to 0.33 ± 0.10 (p < 0.0001 versus PLR; NS versus baseline position). Conclusion: In this proof-of-concept study of healthy participants, the Indicor device, a noninvasive, convenient device that automatically calculates VPR from a finger photoplethysmography signal during a standardized Valsalva maneuver, was sensitive enough to detect the increase in VPR that occurred with an acute central volume load from a PLR. Future studies should examine whether VPR responds differently to a PLR in heart failure patients with abnormal cardiac performance and/or congestion.

Early Endothelial Signaling Transduction in Developing Lung Edema.

The lung promptly responds to edemagenic conditions through functional adaptations that contrast the increase in microvascular filtration. This review presents evidence for early signaling transduction by endothelial lung cells in two experimental animal models of edema, hypoxia exposure, and fluid overload (hydraulic edema). The potential role of specialized sites of the plasma membranes considered mobile signaling platforms, referred to as membrane rafts, that include caveolae and lipid rafts, is presented. The hypothesis is put forward that early changes in the lipid composition of the bilayer of the plasma membrane might trigger the signal transduction process when facing changes in the pericellular microenvironment caused by edema. Evidence is provided that for an increase in the extravascular lung water volume not exceeding 10%, changes in the composition of the plasma membrane of endothelial cells are evoked in response to mechanical stimuli from the interstitial compartment as well as chemical stimuli relating with changes in the concentration of the disassembled portions of structural macromolecules. In hypoxia, thinning of endothelial cells, a decrease in caveolae and AQP-1, and an increase in lipid rafts are observed. The interpretation of this response is that it favors oxygen diffusion and hinder trans-cellular water fluxes. In hydraulic edema, which generates greater capillary water leakages, an increase in cell volume and opposite changes in membrane rafts were observed; further, the remarkable increase in caveolae suggests a potential abluminal-luminal vesicular-dependent fluid reabsorption.

Load-induced fluid pressurisation in hydrogel systems before and after reinforcement by melt-electrowritten fibrous meshes.

Fluid pressure develops transiently within mechanically-loaded, cell-embedding hydrogels, but its magnitude depends on the intrinsic material properties of the hydrogel and cannot be easily altered. The recently developed melt-electrowriting (MEW) technique enables three-dimensional printing of structured fibrous mesh with small fibre diameter (20 µm). The MEW mesh with 20 µm fibre diameter can synergistically increase the instantaneous mechanical stiffness of soft hydrogels. However, the reinforcing mechanism of the MEW meshes is not well understood, and may involve load-induced fluid pressurisation. Here, we examined the reinforcing effect of MEW meshes in three hydrogels: gelatin methacryloyl (GelMA), agarose and alginate, and the role of load-induced fluid pressurisation in the MEW reinforcement. We tested the hydrogels with and without MEW mesh (i.e., hydrogel alone, and MEW-hydrogel composite) using micro-indentation and unconfined compression, and analysed the mechanical data using biphasic Hertz and mixture models. We found that the MEW mesh altered the tension-to-compression modulus ratio differently for hydrogels that are cross-linked differently, which led to a variable change to their load-induced fluid pressurisation. MEW meshes only enhanced the fluid pressurisation for GelMA, but not for agarose or alginate. We speculate that only covalently cross-linked hydrogels (GelMA) can effectively tense the MEW meshes, thereby enhancing the fluid pressure developed during compressive loading. In conclusion, load-induced fluid pressurisation in selected hydrogels was enhanced by MEW fibrous mesh, and may be controlled by MEW mesh of different designs in the future, thereby making fluid pressure a tunable cell growth stimulus for tissue engineering involving mechanical stimulation.

Effect of fluid load on the prognosis of children with sepsis-associated acute kidney injury undergoing continuous renal replacement therapy. / ä¸åŒæ¶²ä½“è´Ÿè·çŠ¶æ€å¯¹æŒç»­è‚¾æ›¿ä»£æ²»ç–—è„“æ¯’ç—‡ç›¸å ³æ€¥æ€§è‚¾æŸä¼¤æ‚£å„¿é¢„åŽçš„å½±å“.

OBJECTIVES: To evaluate the effect of fluid load on the prognosis of children with sepsis-associated acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT). METHODS: A total of 121 children who underwent CRRT for sepsis-associated AKI from August 2018 to March 2021 were enrolled in the retrospective study. According to the fluid load from admission or disease progression to CRRT, they were divided into three groups: low fluid load (fluid load: <5%; n=35), high fluid load (fluid load: 5% - <10%; n=35), and fluid overload (fluid load: ≥10%; n=51). Baseline data and clinical biochemical data before CRRT were collected for comparison and analysis. The Kaplan-Meier survival curve analysis was used for comparison of 28-day survival between groups. The multivariate logistic regression model was used to identify the influencing factors for the prognosis of the children. RESULTS: The survival analysis showed that the fluid overload group had a significantly higher 28-day mortality rate than the low fluid load and high fluid load groups (P<0.05). The multivariate logistic regression analysis showed that an increase in fluid overload volume was a risk factor for increased 28-day mortality in the fluid overload group, while earlier initiation of CRRT was a protective factor (P<0.05). CONCLUSIONS: Fluid overload before CRRT may increase the mortality in children with sepsis-associated AKI, and CRRT should be performed for these children as early as possible.

Management of Hemorrhagic Shock: Physiology Approach, Timing and Strategies.

Hemorrhagic shock (HS) management is based on a timely, rapid, definitive source control of bleeding/s and on blood loss replacement. Stopping the hemorrhage from progressing from any named and visible vessel is the main stem fundamental praxis of efficacy and effectiveness and an essential, obligatory, life-saving step. Blood loss replacement serves the purpose of preventing ischemia/reperfusion toxemia and optimizing tissue oxygenation and microcirculation dynamics. The "physiological classification of HS" dictates the timely management and suits the 'titrated hypotensive resuscitation' tactics and the 'damage control surgery' strategy. In any hypotensive but not yet critical shock, the body's response to a fluid load test determines the cut-off point between compensation and progression between the time for adopting conservative treatment and preparing for surgery or rushing to the theater for rapid bleeding source control. Up to 20% of the total blood volume is given to refill the unstressed venous return volume. In any critical level of shock where, ab initio, the patient manifests signs indicating critical physiology and impending cardiac arrest or cardiovascular accident, the balance between the life-saving reflexes stretched to the maximum and the insufficient distal perfusion (blood, oxygen, and substrates) remains in a liable and delicate equilibrium, susceptible to any minimal change or interfering variable. In a cardiac arrest by exsanguination, the core of the physiological issue remains the rapid restoration of a sufficient venous return, allowing the heart to pump it back into systemic circulation either by open massage via sternotomy or anterolateral thoracotomy or spontaneously after aorta clamping in the chest or in the abdomen at the epigastrium under extracorporeal resuscitation and induced hypothermia. This is the only way to prevent ischemic damage to the brain and the heart. This is accomplishable rapidly and efficiently only by a direct approach, which is a crush laparotomy if the bleeding is coming from an abdominal +/- lower limb site or rapid sternotomy/anterolateral thoracotomy if the bleeding is coming from a chest +/- upper limbs site. Without first stopping the bleeding and refilling the heart, any further exercise is doomed to failure. Direct source control via laparotomy/thoracotomy, with the concomitant or soon following venous refilling, are the two essential, initial life-saving steps.

Left ventricular depression and pulmonary edema in rats after short-term normobaric hypoxia: effects of adrenergic blockade and reduced fluid load.

Acute normobaric hypoxia may induce pulmonary injury with edema (PE) and inflammation. Hypoxia is accompanied by sympathetic activation. As both acute hypoxia and high plasma catecholamine levels may elicit PE, we had originally expected that adrenergic blockade may attenuate the severity of hypoxic pulmonary injury. In particular, we investigated whether administration of drugs with reduced fluid load would be beneficial with respect to both cardiocirculatory and pulmonary functions in acute hypoxia. Rats were exposed to normobaric hypoxia (10% O2) over 1.5 or 6 h and received 0.9% NaCl or adrenergic blockers either as infusion (1 ml/h, increased fluid load) or injection (0.5 ml, reduced fluid load). Control animals were kept in normoxia and received infusions or injections of 0.9% NaCl. After 6 h of hypoxia, LV inotropic function was maintained with NaCl injection but decreased significantly with NaCl infusion. Adrenergic blockade induced a similar LV depression when fluid load was low, but did not further deteriorate LV depression after 6 h of infusion. Reduced fluid load also attenuated pulmonary injury after 6 h of hypoxia. This might be due to an effective fluid drainage into the pleural space. Adrenergic blockade could not prevent PE. In general, increased fluid load and impaired LV inotropic function promote the development of PE in acute hypoxia. The main physiologic conclusion from this study is that fluid reduction under hypoxic conditions has a protective effect on cardiopulmonary function. Consequently, appropriate fluid management has particular importance to subjects in hypoxic conditions.

Articular Cartilage Friction, Strain, and Viability Under Physiological to Pathological Benchtop Sliding Conditions.

In vivo, articular cartilage is exceptionally resistant to wear, damage, and dysfunction. However, replicating cartilage's phenomenal in vivo tribomechanics (i.e., high fluid load support, low frictions and strains) and mechanobiology on the benchtop has been difficult, because classical testing approaches tend to minimize hydrodynamic contributors to tissue function. Our convergent stationary contact area (cSCA) configuration retains the ability for hydrodynamically-mediated processes to contribute to interstitial hydration recovery and tribomechanical function via 'tribological rehydration'. Using the cSCA, we investigated how in situ chondrocyte survival is impacted by the presence of tribological rehydration during the reciprocal sliding of a glass counterface against a compressively loaded equine cSCA cartilage explant. When tribological rehydration was compromised during testing, by slow-speed sliding, 'pathophysiological' tribomechanical environments and high surface cell death were observed. When tribological rehydration was preserved, by high-speed sliding, 'semi-physiological' sliding environments and suppressed cell death were realized. Inclusion of synovial fluid during testing fostered 'truly physiological' sliding outcomes consistent with the in vivo environment but had limited influence on cell death compared to high-speed sliding in PBS. Subsequently, path analysis identified friction as a primary driver of cell death, with strain an indirect driver, supporting the contention that articulation mediated rehydration can benefit both the biomechanical properties and biological homeostasis of cartilage. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00671-2.

The effects of a home-based care model on fluid load in hemodialysis patients.

BACKGROUND: Fluid management in hemodialysis patients is critical, but there are no optimal care protocols. The aim of this study was to investigate the impact of a home-based care model on the fluid loads in patients undergoing sustained hemodialysis. METHODS: This is a single-center, randomized, controlled clinical study. 124 patients who underwent maintenance hemodialysis were randomized into an experimental group (EG) and a control group (CG) (n=62 for each group). The EG underwent a home-based care model, and the CG was cared for using a routine nursing model. They were compared in terms of their blood pressure, BMI, pulse wave velocity (PWV), and N-terminal (NT)-pro hormone BNP (NT-proBNP) levels before the nursing and at 12 months of follow-up. RESULTS: There was no significant difference in the baseline data between the two groups (P>0.05). At 12 months of intervention, the EG had better systolic blood pressure (139±9 mmHg vs. 144±13 mmHg, P=0.04) and NT-proBNP levels (6148 pg/ml vs. 8552 pg/ml, P=0.01) than the CG. There was no significant difference between the two groups in terms of BMI, DBP or PWV or in their adverse event rates. CONCLUSION: The home-based care model is beneficial for fluid management in hemodialysis patients.

Comparative Tribology: Articulation-induced rehydration of cartilage across species.

Articular cartilage is a robust tissue that facilitates load distribution and wear-free articulation in diarthrodial joints. These biomechanical capabilities are fundamentally tied to tissue hydration, whereby high interstitial fluid pressures and fluid load support facilitate the maintenance of low tissue strains and frictions. Our recent ex vivo studies of cartilage sliding biomechanics using the convergent stationary contact area (cSCA) configuration, first introduced by Dowson and colleagues, unexpectedly demonstrated that sliding alone can promote recovery of interstitial pressure and lubrication lost to static compression through a mechanism termed 'tribological rehydration.' Although exclusively examined in bovine stifle cartilage to date, we hypothesized that tribological rehydration, i.e., the ability to recover/modulate tissue strains and lubrication through sliding, is a universal behavior of articular cartilage. This study aimed to establish if, and to what extent, sliding-induced tribological rehydration is conserved in articular cartilage across a number of preclinical animal species/models and diarthrodial joints. Using a comparative approach, we found that articular cartilage from equine, bovine, ovine, and caprine stifles, and porcine stifle, hip, and tarsal joints all exhibited remarkably consistent sliding speed-dependent compression/strain recovery and lubrication behaviors under matched contact stresses (0.25 MPa). All cartilage specimens tested supported robust, tribological rehydration during high-speed sliding (>30 mm/s), which as a result of competitive recovery of interstitial lubrication, promoted remarkable decreases in kinetic friction during continuous sliding. The conservation of tribological rehydration across mammalian quadruped articular cartilage suggests that sliding-induced recovery of interstitial hydration represents an important tissue adaptation and largely understudied contributor to the biomechanics of cartilage and joints.

Range-of-motion affects cartilage fluid load support: functional implications for prolonged inactivity.

OBJECTIVE: Joint movements sustain cartilage fluid load support (FLS) through a combination of contact migration and periodic bath exposure. Although there have been suggestions that small involuntary movements may disrupt load-induced exudation during prolonged inactivity, theoretical studies have shown otherwise. This work used well-controlled explant measurements to experimentally test an existing hypothesis that the range-of-motion must exceed the contact length to sustain non-zero FLS. METHOD: Smooth glass spheres (1.2-3.2 mm radius) were slid at 1.5 mm/s (Péclet number >100) against bovine osteochondral explants under varying normal loads (0.05-0.1 N) and migration lengths (0.05-7 mm) using a custom instrument. In situ deformation measurements were used to quantify FLS. RESULTS: Non-zero FLS was maintained at migration lengths as small as 0.05 mm or <10% the typical contact diameter. FLS peaked when track lengths exceeded 10 times the contact diameter. For migration lengths below this threshold, FLS decreased with increased contact stress. CONCLUSIONS: Migration lengths far smaller than the contact diameter can sustain non-zero FLS, which, from a clinical perspective, indicates that fidgeting and drifting can mitigate exudation and loss of FLS during prolonged sitting and standing. Nonetheless, FLS decreased monotonically with decreased migration length when migration lengths were less than 10 times the contact diameter. The results demonstrate: (1) potential biomechanical benefits from small movement (e.g., drifting and fidgeting); (2) the quantitative limits of those benefits; (3) and how loads, movement patterns, and mobility likely impact long term FLS.

Effects of Water Loading on Observed and Predicted Plasma Sodium, and Fluid and Urine Cation Excretion in Healthy Individuals.

RATIONALE & OBJECTIVE: The discovery of sodium storage without concurrent water retention suggests the presence of an additional compartment for sodium distribution in the body. The osmoregulatory role of this compartment under hypotonic conditions is not known. STUDY DESIGN: Experimental interventional study. SETTING & PARTICIPANTS: Single-center study of 12 apparently healthy men. INTERVENTION: To investigate whether sodium can be released from its nonosmotic stores after a hypotonic fluid load, a water-loading test (20mL water/kg in 20 minutes) was performed. OUTCOMES: During a 240-minute follow-up, we compared the observed plasma sodium concentration ([Na+]) and fluid and urine cation excretion with values predicted by the Barsoum-Levine and Nguyen-Kurtz formulas. These formulas are used for guidance of fluid therapy during dysnatremia, but do not account for nonosmotic sodium stores. RESULTS: 30 minutes after water loading, mean plasma [Na+] decreased 3.2±1.6 (SD) mmol/L, after which plasma [Na+] increased gradually. 120 minutes after water loading, plasma [Na+] was significantly underestimated by the Barsoum-Levine (-1.3±1.4mmol/L; P=0.05) and Nguyen-Kurtz (-1.5±1.5mmol/L; P=0.03) formulas. In addition, the Barsoum-Levine and Nguyen-Kurtz formulas overestimated urine volume, while cation excretion was significantly underestimated, with a cation gap of 57±62 (P=0.009) and 63±63mmol (P=0.005), respectively. After 240 minutes, this gap was 28±59 (P=0.2) and 34±60mmol (P=0.08), respectively. LIMITATIONS: The compartment from which the mobilized sodium originated was not identified, and heterogeneity in responses to water loading was observed across participants. CONCLUSIONS: These data suggest that healthy individuals are able to mobilize osmotically inactivated sodium after an acute hypotonic fluid load. Further research is needed to expand knowledge about the compartment of osmotically inactivated sodium and its role in osmoregulation and therapy for dysnatremias. FUNDING: This investigator-initiated study was partly supported by a grant from Unilever Research and Development Vlaardingen, The Netherlands B.V. (MA-2014-01914).

Fluid load support does not explain tribological performance of PVA hydrogels.

The application of hydrogels as articular cartilage (AC) repair or replacement materials is limited by poor tribological behaviour, as it does not match that of native AC. In cartilage, the pressurisation of the interstitial fluid is thought to be crucial for the low friction as the load is shared between the solid and liquid phase of the material. This fluid load support theory is also often applied to hydrogels. However, this theory has not been validated as no experimental evidence directly relates the pressurisation of the interstitial fluid to the frictional response of hydrogels. This lack of understanding about the governing tribological mechanisms in hydrogels limits their optimised design. Therefore, this paper aims to provide a direct measure for fluid load support in hydrogels under physiologically relevant sliding conditions. A photoelastic method was developed to simultaneously measure the load on the solid phase of the hydrogel and its friction coefficient and thus directly relate friction and fluid load support. The results showed a clear distinction in frictional behaviour between the different test conditions, but results from photoelastic images and stress-relaxation experiments indicated that fluid load support is an unlikely explanation for the frictional response of the hydrogels. A more appropriate explanation, we hypothesized, is a non-replenished lubricant mechanism. This work has important implications for the tribology of cartilage and hydrogels as it shows that the existing theories do not adequately describe the tribological behaviour of hydrogels. The developed insights can be used to optimise the tribological performance of hydrogels as articular cartilage implants.

Research on torsional friction behavior and fluid load support of PVA/HA composite hydrogel.

Hydrogels have been extensively studied for use as synthetic articular cartilage. This study aimed to investigate (1) the torsional friction contact state and the transformation mechanism of PVA/HA composite hydrogel against CoCrMo femoral head and (2) effects of load and torsional angle on torsional friction behavior. The finite element method was used to study fluid load support of PVA/HA composite hydrogel. Results show fluid loss increases gradually of PVA/HA composite hydrogel with torsional friction time, leading to fluid load support decreases. The contact state changes from full slip state to stick-slip mixed state. As the load increases, friction coefficient and adhesion zone increase gradually. As the torsional angle increases, friction coefficient and slip trend of the contact interface increase, resulting in the increase of the slip zone and the reduction of the adhesion zone. Fluid loss increases of PVA/HA composite hydrogel as the load and the torsional angle increase, which causes the decrease of fluid load support and the increase of friction coefficient.

Use of near-infrared spectroscopy in predicting response to intravenous fluid load in anaesthetized infants.

INTRODUCTION: The prediction of fluid responsiveness in paediatrics and infants remains problematic. We sought to test the validity of the measurement of StcO2 as a predictive parameter of fluid responsiveness in infants less than one year old during non-cardiac surgery. MATERIALS AND METHODS: This was a prospective observational study on infants aged less than 1 year without any cardiac disease during the intraoperative period of non-cardiac surgery. Cerebral oxygen saturation (StcO2) was obtained using infrared spectroscopic INVOS® monitors. Reference values were obtained 10 minutes after intubation. Fluid load indications were dependent on the anaesthesiologist caring for the patient. The objective of this study was to determine the accuracy of StcO2 values before vascular filling (StcO2B) and the difference in StcO2 values between the reference value and before vascular filling (ΔStcO2), in predicting vascular filling response defined as an increase in mean arterial pressure over 15%. Statistical analysis was carried out using ROC curve analysis with determination of grey zones. RESULTS: Twenty-nine patients were eligible for this study, 23 were included in the study (one intravenous fluid challenge per patient). There were 10 responders and 13 non-responders. The StcO2B and the ΔStcO2 were significantly different between responders and non-responders. Analysis of the ROC curve found an area under the curve of 0.75 [95% CI 0.56 to 0.95] for StcO2B and 0.83 [95% CI 0.66 to 0.99] for ΔStcO2. The grey-areas were [59-78] and [16-28] for StcO2B and ΔStcO2. CONCLUSION: NIRS appears to be an interesting additional tool for predicting an increase of blood pressure in response to intraoperative fluid challenge in infants less than one year old.

Finite element analysis of the meniscectomised tibio-femoral joint: implementation of advanced articular cartilage models.

The article presents advanced computer simulations aimed at the accurate modelling of human tibio-femoral joints (TFJs) in terms of anatomy, physiological loading and constitutive behaviour of the tissues. The main objective of this research is to demonstrate the implications that the implementation of different articular cartilage models have on the prediction of the joint response. Several biphasic material constitutive laws are tested using a finite element package and compared to the monophasic linear elastic description, often still used to predict the instantaneous response of the cartilage in 3D knee models. Thus, the importance of adequately capturing the contribution of the interstitial fluid support is proved using a simplified 3D model; subsequently, a biphasic poroviscoelastic non-linear constitutive law is implemented to study the response of a patient-specific TFJ subjected to simplified walking cycles. The time evolution of stresses, pore pressure, contact areas and joint displacements is captured and compared with existing meniscectomised knee models. Contact pressures and areas obtained using the developed numerical simulations are in agreement with the existing experimental evidence for meniscectomised human knee joints. The results are then used to predict the most likely site for the origin of mechanical damage, i.e. the medial cartilage surface for the specific case analysed in the present contribution. Finally, future research directions are suggested.