Limited Flow Research Articles

Circulatory Response to Rapid Volume Expansion and Cardiorespiratory Fitness in Fontan Circulation

The role of dysfunction of the single ventricle in Fontan failure is incompletely understood. We aimed to evaluate hemodynamic responses to preload increase in Fontan circulation, to determine whether circulatory limitations in different locations identified by experimental preload increase are associated with cardiorespiratory fitness (CRF), and to assess the impact of left versus right ventricular morphology. In 38 consecutive patients (median age = 16.6 years, 16 females), heart catheterization was supplemented with a rapid 5-mL/kg body weight volume expansion. Central venous pressure (CVP), ventricular end-diastolic pressure (VEDP), and peak systolic pressure were averaged for 15‒30 s, 45‒120 s, and 4‒6 min (steady state), respectively. CRF was assessed by peak oxygen consumption (VO2peak) and ventilatory threshold (VT). Median CVP increased from 13 mmHg at baseline to 14.5 mmHg (p < 0.001) at steady state. CVP increased by more than 20% in eight patients. Median VEDP increased from 10 mmHg at baseline to 11.5 mmHg (p < 0.001). Ten patients had elevated VEDP at steady state, and in 21, VEDP increased more than 20%. The transpulmonary pressure difference (CVP‒VEDP) and CVP were consistently higher in patients with right ventricular morphology across repeated measurements. CVP at any stage was associated with VO2peak and VT. VEDP after volume expansion was associated with VT. Preload challenge demonstrates the limitations beyond baseline measurements. Elevation of both CVP and VEDP are associated with impaired CRF. Transpulmonary flow limitation was more pronounced in right ventricular morphology. Ventricular dysfunction may contribute to functional impairment after Fontan operation in young adulthood.ClinicalTrials.govidentifier NCT02378857

Properties of Humic Acids in Meadow Soils Irrigated with the Slope-and-Flooding System

The still-advancing soil degradation and the related losses of soil organic carbon stocks due to the limited inflow of organic residues in agro-ecosystems encourage more and more soil protection. Establishing meadow ecosystems is one of the key methods of agricultural land use preventing losses of organic carbon in soils. Based on the research on the properties of humic acids, it is possible to determine the advancement of the processes of transformation and decomposition of soil organic matter. The obtained results may allow for the development of a soil protection strategy and more effective sequestration of organic carbon. Therefore, the aim of the research was to determine the properties of humic acids defining the quality of organic matter of meadow soils irrigated for 150 years with the slope-and-flooding system. The research was performed based on the soils (Albic Brunic Arenosol) sampled from Europe’s unique complex of permanent irrigated grasslands (the same irrigation management for 150 years), applying the slope-and-flooding system: the Czerskie Meadows. The soil samples were assayed for the content of total organic carbon (TOC) and the particle size distribution. HAs were extracted with the Schnitzer method and analysed for the elemental composition, spectrometric parameters in the UV-VIS (ultraviolet-visible) range, hydrophilic and hydrophobic properties and the infrared spectra. The research results showed that the HAs properties depend on the depth and the distance from the irrigation ditch. The HAs of soils sampled from the depth of 0–10 cm were identified with a lower “degree of maturity” as compared with the HAs of soils sampled from the depth of 20–30 cm, reflected by the values of atomic ratios (H/C, O/C, O/H), absorbance coefficients, and the FT-IR (Fourier transform infrared) spectra. The mean values of the H/C ratio in the HAs molecules of soils sampled from the depth of 20–30 cm were lower by 8.2% than those from the depth of 0–10 cm. The mean values of the absorbance coefficient A4/6 in the HAs molecules of soils sampled from the depth of 20–30 cm were lower by 9.6% than in the HAs molecules of soils sampled from the depth of 0–10 cm. The HAs molecules of the soils sampled 25 m from the irrigation ditch were identified with a higher degree of humification, as compared with the HAs of the soils sampled 5 m from the irrigation ditch. The results identified that humic acids produced in the many-year irrigated sandy soils were identified with a high degree of humification, which proves the relative stability of the soil’s organic matter. It confirms the importance of meadow soils for the carbon sequestration process. It should also be emphasized that the research area is interesting, although hardly described in terms of organic matter properties. Further and more detailed applicable research is planned, e.g., monitoring of total organic carbon content and comparing the properties of irrigated and non-irrigated meadow soils. Continuity of research is necessary to assess the direction of the soil organic matter transformation in such a unique ecosystem. The obtained results may allow for the development of, inter alia, models of agricultural practices that increase carbon sequestration in soils. In the long term, this will allow for greater environmental benefits and, thus, also increased financial benefits.

Cathodoluminescence in Ultrafast Electron Microscopy.

Implementing the modern technologies of light-emitting devices, light harvesting, and quantum information processing requires the understanding of the structure-function relations at spatial scales below the optical diffraction limit and time scales of energy and information flows. Here, we distinctively combine cathodoluminescence (CL) with ultrafast electron microscopy (UEM), termed CL-UEM, because CL and UEM synergetically afford the required spectral and spatiotemporal sensitivities, respectively. For color centers in nanodiamonds, we demonstrate the measurement of CL lifetime with a local sensitivity of 50 nm and a time resolution of 100 ps. It is revealed that the emitting states of the color centers can be populated through charge transfer among the color centers across diamond lattices upon high-energy electron beam excitation. The technical advance achieved in this study will facilitate the specific control over energy conversion at nanoscales, relevant to quantum dots and single-photon sources.

766 Distal embolization protection systems. A rare complication

Abstract Aims The no reflow phenomenon is a not rare complication that occurs in up to 30% of patients with acute coronary syndrome undergoing myocardial reperfusion by percutaneous coronary intervention. The use of coronary artery thrombus aspiration or distal embolization protection systems has reduced the risk of distal embolization and no-reflow phenomenon. Methods and results We describe the case of a 77 year old female suffering from hypertension presented at our emergency department for inferior STEMI. An urgent coronary angiography was performed, showing a three-vessel coronary artery disease with right coronary artery sub-occluded in the middle segment (culprit lesion), with a voluminous endoluminal minus image, as intracoronary thrombosis. Before performing the coronary angioplasty, a Spider FX3 filter was placed on the distal segment of the right coronary artery; thrombus aspiration was performed, which was ineffective, then angioplasty and Zotarolimus eluting stent implantation in the mid segment of the right coronary artery. After stent implantation, an image of minus was highlighted inside the basket of the filter, as a migrated and incarcerated thrombotic formation; then, the filter was removed. During the removal of the filter, longitudinal crush of the distal portion of the stent is caused, with limitation of the downstream flow, in the absence of haemodynamic instability. The stent was recrossed with Fielder XT guidewire supported by Turnpike LP Microcatheter. Multiple dilations werenperformed with semi-compliant and non-compliant increasing-caliber balloons and then Zotarolimus eluting stent implantation, in partial overlap with the distal portion of the previously implanted stent, with TIMI flow 3. The echocardiogram showed a normal global systolic function, with alterations in regional kinetics. On the 6th day, angioplasty and Zotarolimus eluting stent implantation was performed on the mid-proximal segment of the left anterior descending artery. During the hospitalization the patient was stable and has been discharged in good condition on the ninth day. Conclusions The interest of this case is the evidence of a rare complication related to the use of distal embolization protection system, probably due to an incomplete closure of the filter before removal, due to the high amount of thrombotic material inside it. The rapid recrossing of the stent after the longitudinal crush, the angioplasty and the second stent implantation, led to a quick flow restoration, without haemodynamic and clinical consequences on the patient's outcome.

472 Coronary disease in ADPKD patient: a giant coronary aneurysm

Abstract Aims Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disorder driven by mutation of one of two genes: PKD1, which codifies polycystin-1, and PKD2, which codifies polycystin-2. The mutated proteins determine the formation of multiple renal cysts with a consequent decline in kidney function eventually leading to end-stage renal disease (ESRD). In the last decades the cardiovascular complications of ADPKD are emerging as the leading cause of death, but coronary artery disease (CAD) remains to be an uncommon complication. Methods and results A 60-year-old male patient affected by ADPKD, in dialysis treatment for ESRD, was admitted in 2020 to our hospital for invasive coronary angiography (ICA), checking eligibility for kidney transplantation. He had a previous history of hypertension and chronic ischaemic cardiomyopathy. ICA performed in 2017 for unstable angina assessed ectasiant coronary arteries with diffuse atherosclerotic disease (Figure 1), determining significant stenosis of the proximal left anterior descending artery and proximal circumflex artery, treated with percutaneous coronary intervention (PCI). In 2020 was so repeated ICA, that evidenced a good result of the previous PCI, but pointed out a severe progression of ectasiant disease, which led to formation of giant aneurysm of the proximal tract of the right coronary artery, assessed at 3.8 cm × 2.5 cm (Figure 2), fistulizing to the right atrium and determining significant flow limitation in the following part of the right coronary artery. The absence of any symptoms and the lack of evidence of ongoing heart dysfunction, led our team to indicate conservative management and angiography follow-up. Conclusions Cardiovascular disease is a major cause of morbidity and death in ADPKD, underlying a tendency towards accelerated atherosclerosis, but wide data about coronary involvement are still lacking. ADPKD patients seem to have an increased risk of developing coronary aneurisms, but either due to the expression of mutated proteins in arterial smooth cells, to the accelerated atherosclerotic disease or to the combination of both, is still controversial. Consequently, it is difficult to differentiate the underlying pathophysiology of aneurysm formation in an individual patient and to speculate whether ADPKD patients have an increased risk of developing coronary aneurysms independent of their accelerated atherosclerotic process.

The role of inspiratory capacity and tidal flow in diagnosing exercise ventilatory limitation in Cystic Fibrosis

BackgroundExercise ventilatory limitation conventionally defined by reduced breathing reserve (BR) may underestimate the effect of lung disease on exercise capacity in patients with mild to moderate obstructive lung diseases. ObjectiveTo investigate whether ventilatory limitation may be present despite a normal BR in Cystic Fibrosis (CF). MethodsTwenty adult CF patients (age 16-58y) with a wide range of pulmonary obstruction severity completed a symptom-limited incremental exercise test on a cycle ergometer. Operating lung volumes were derived from inspiratory capacity (IC) measurement during exercise and exercise tidal flow volume loop analysis.Results: six patients had a severe airway obstruction (FEV1<45% predicted) and conventional evidence of ventilatory limitation (low BR). Fourteen patients had mild to moderate-severe airway obstructive (FEV1 46–103% predicted), and a normal BR [12–62 L/min, BR% (17–40)]. However, dynamic respiratory mechanics demonstrated that even CF patients with mild to moderate-severe lung disease had clear evidence of ventilatory limitation during exercise. IC was decreased by (median) 580 ml (range 90–1180 ml) during exercise, indicating dynamic hyperinflation. Inspiratory reserve volume at peak exercise was 445 ml (241–1350 ml) indicating mechanical constraint on the respiratory system. The exercise tidal flow met or exceeded the expiratory boundary of the maximal flow volume loop over 72% of the expiratory volume (range 40–90%), indicating expiratory flow limitation. ConclusionReduced BR as a sole criterion underestimates ventilatory limitation during exercise in mild to moderate-severe CF patients. Assessment of dynamic respiratory mechanics during exercise revealed ventilatory limitation, present even in patients with mild obstruction.

Functional diagnostics of the respiratory system in chronic obstructive pulmonary disease

The article deals with the pathophysiology of chronic obstructive pulmonary disease (COPD), modern possibilities of functional methods in COPD, including the diagnosis of small airway dysfunction and expiratory air flow limitation with quiet breathing by impulse oscillometry, and also describes the characteristic changes in the indicators of pulmonary functional tests in COPD.

Overnight variation in tidal expiratory flow limitation in COPD patients and its correction: an observational study

BackgroundTidal expiratory flow limitation (EFLT) is common among COPD patients. Whether EFLT changes during sleep and can be abolished during home ventilation is not known.MethodsCOPD patients considered for noninvasive ventilation used a ventilator which measured within-breath reactance change at 5 Hz (∆Xrs) and adjusted EPAP settings to abolish EFLT. Participants flow limited (∆Xrs > 2.8) when supine underwent polysomnography (PSG) and were offered home ventilation for 2 weeks. The EPAP pressure that abolished EFLT was measured and compared to that during supine wakefulness. Ventilator adherence and subjective patient perceptions were obtained after home use.ResultsOf 26 patients with supine EFLT, 15 completed overnight PSG and 10 the home study. In single night and 2-week home studies, EFLT within and between participants was highly variable. This was unrelated to sleep stage or body position with only 14.6% of sleep time spent within 1 cmH2O of the awake screening pressure. Over 2 weeks, mean EPAP was almost half the mean maximum EPAP (11.7 vs 6.4 cmH2O respectively). Group mean ∆Xrs was ≤ 2.8 for 77.3% of their home use with a mean time to abolish new EFLT of 5.91 min. Adherence to the ventilator varied between 71 and 100% in prior NIV users and 36–100% for naïve users with most users rating therapy as comfortable.ConclusionsTidal expiratory flow limitation varies significant during sleep in COPD patients. This can be controlled by auto-titrating the amount of EPAP delivered. This approach appears to be practical and well tolerated by patients.Trial registration: The trial was retrospectively registered at CT.gov NCT04725500.

Insights Into Endovascular Management of Superior Vena Cava Obstructions.

Superior vena cava obstruction results from any limitation of blood flow through the superior vena cava. Circulation to the heart may persist through various collateral vessels whose development depends on the level of obstruction. Depending on the level and degree of occlusive disease, the severity of clinical symptoms may vary considerably, up to lethal. Etiologies have changed dramatically in recent years, mainly due to the increasing use of intravascular devices. However, guidelines for treatment are lacking, and various options are available. Endovascular therapies developed considerably in recent years, may offer a rapid improvement in symptoms and proved to be safe. However, knowledge and selection of appropriate techniques are essential to venous angioplasty, involving specific tools to guarantee satisfying outcomes. This review aims to discuss the particular venous anatomy of the upper body, the physiopathology of superior vena cava obstruction, and specificities of endovascular treatment compared with other management options.

Experimental Investigation of the Heat Transfer Characteristics and Operation Limits of a Fork-Type Heat Pipe for Passive Cooling of a Spent Fuel Pool

A fork-type heat pipe (FHP) is a passive heat-transport and air-cooling device used to remove the decay heat of spent nuclear fuels stored in a liquid pool during a station blackout. FHPs have a unique geometrical design to resolve the significant mismatch between the convective heat transfer coefficients of the evaporator and condenser parts. The evaporator at the bottom is a single heat-exchanger tube, whereas the condenser at the top consists of multiple finned tubes to maximize the heat transfer area. In this study, the heat transfer characteristics and operating limits of an FHP device were investigated experimentally. A laboratory-scale model of an FHP was manufactured, and a series of tests were conducted while the temperature was varied to simulate a spent fuel pool. As an index of the average heat transfer performance, the loop conductance was computed from the measurement data. The results show that the loop conductance of the FHP increased with the heat transfer rate but deteriorated significantly at the operating limit. The maximum attainable heat transfer rate of the unit FHP model was accurately predicted by the existing correlations of the counter-current flow limit for a single-rod-type heat pipe. In addition, the instant heat transfer behaviors of the FHP model under different temperature conditions were examined to interpret the measured loop conductance variation and operating limit.

Heat transfer analysis of MHD viscous fluid in a ciliated tube with entropy generation

This investigation aims to explain the study of heat transfer and entropy generation of Magnetohydrodynamics (MHD) viscous fluid flowing through a ciliated tube. Heat transfer study has massive importance in various biomedical and biological industry problems. The metachronal wave propagation is the leading cause behind this viscous creeping flow. A low Reynolds number is used as the inertial forces are weaker than viscous forces, and also, creeping flow limitations are fulfilled. For the cilia movement, a very large wavelength of a metachronal wave is taken into account. Entropy generation is used to examine the heat transfer through the flow. Numerical solutions are calculated by using MATHEMATICA. Exact mathematical solutions are calculated and analyzed with the help of graphs. Streamlines are also plotted. An axially symmetric flow as well as temperature profile is revealed through the graphical solutions. Both velocity and temperature profiles attain maximum value in the center of this ciliated tube that eventually declines toward the boundaries.

Primary metabolism and initial development of grafted black pepper seedlings

The production of black pepper seedlings through grafting is a promising strategy to mitigate the effect of environmental stresses, such as drought, that limit its cultivation. However, studies on compatibility between grafts and rootstocks are still scarce, especially considering the wild species of the genus Piper and the cultivated genotypes of black pepper. The objective of this work was to evaluate the relationship between primary metabolism and the development of black pepper seedlings obtained through intra- and interspecific grafting. The method used was that of cleft lateral grafting, as graft the Bragantina cultivar, better known in the world as ‘Panniyur 1’, and ‘Kottanadan’ cultivar and three wild species (Piper hispidum, Piper aduncum and Piper tuberculatum) were used as root-stock. As a control, ´Bragantina` was grafted onto itself (homograft). The experiment was carried out for 110 days and the seedlings were evaluated for development, gas exchange, and carbohydrate allocation. The rootstock influences the development and primary metabolism of seedlings. P. aduncum showed greater initial compatibility among wild species, due to less impediment to carbohydrate flow. P. tuberculatum showed early incompatibility, as the grafts died. The seedlings grafted on P. hispidum and 'Kottanadan' had initial compatibility with an average of 78% survival and 60% budding, but they may have late incompatibility due to limitation of carbohydrate flow.

Development Length of Fluids Modelled by the gPTT Constitutive Differential Equation

In this work, we present a numerical study on the development length (the length from the channel inlet required for the velocity to reach 99% of its fully-developed value) of a pressure-driven viscoelastic fluid flow (between parallel plates) modelled by the generalised Phan–Thien and Tanner (gPTT) constitutive equation. The governing equations are solved using the finite-difference method, and, a thorough analysis on the effect of the model parameters α and β is presented. The numerical results showed that in the creeping flow limit (Re=0), the development length for the velocity exhibits a non-monotonic behaviour. The development length increases with Wi. For low values of Wi, the highest value of the development length is obtained for α=β=0.5; for high values of Wi, the highest value of the development length is obtained for α=β=1.5. This work also considers the influence of the elasticity number.

Quantifying tidal expiratory flow limitation using a vector-based analysis technique

Objective. Tidal expiratory flow limitation (EFLT) is commonly identified by tidal breaths exceeding the forced vital capacity (FVC) loop. This technique, known as the Hyatt method, is limited by the difficulties in defining the FVC and tidal flow-volume (TV) loops. The vector-based analysis (VBA) technique described and piloted in this manuscript identifies and quantifies EFLT as tidal breaths that conform to the contour of the FVC loop. Approach. The FVC and TV loops are interpolated to generate uniformly spaced plots. VBA is performed to determine the smallest vector difference between each point on the FVC and TV curves, termed the flow reserve vector (FRV). From the FVC point yielding the lowest FRV, the tangential angles of the FVC and TV segments are recorded. If the TV and FVC loops become parallel, the difference between the tangential angles tends towards zero. We infer EFLT as parallel TV and FVC segments where the FRV is < 0.1 and the tangential angle is within ±18 degrees for ≥5% of TV. EFLT is quantified by the percent of TV loop fulfilling these criteria. We compared the presence and degree of EFLT at rest and during peak exercise using the Hyatt method and our VBA technique in 25 healthy subjects and 20 subjects with moderate-severe airflow obstruction. Main results. Compared to the Hyatt method, our VBA technique reported a significantly lower degree of EFLT in healthy subjects during peak exercise, and in obstructed subjects at rest and during peak exercise. In contrast to the Hyatt method, our VBA technique re-classified five subjects (one in the healthy group and four in the obstructed group) as demonstrating EFLT. Significance. Our VBA technique provides an alternative approach to determine and quantify EFLT which may reduce the overestimation of the degree EFLT and more accurately identify subjects experiencing EFLT.

Data-Driven Nonparametric Joint Chance Constraints for Economic Dispatch with Renewable Generation

This article presents data-driven nonparametric joint chance constraints (JCCs) for ramp-constrained economic dispatch. Power generated by renewable sources, such as solar farms, is modeled as an uncertain parameter that may not belong to any parametric class of probability functions. Thus, transmission line flow limitation, which time-independent constraints, are formulated as nonparametric JCCs joint over unknown cumulative distribution functions of renewable generation sources. In addition, thermal units' time-dependent spinning reserve constraints are modeled as nonparametric JCCs joint over scheduling time periods. An approach is presented based on a multivariate kernel density estimator to convert economic dispatch with data-driven nonparametric JCCs into an optimization model solvable by standard solvers. A reduced, more conservative risk level is calculated to ensure JCCs' satisfaction, given the distance between true unknown and estimated cumulative distribution functions by kernel density estimator. An initiation strategy is applied to speed up the optimization solution time. Numerical results show that using data-driven nonparametric JCCs enhances system reliability significantly as compared to using individual chance constraints and parametric JCCs.

Is a passivated back contact always beneficial for Cu (In,Ga)Se2solar cells?

AbstractUltrathin CIGSe solar cells on TCOs (transparent conductive oxides) have many promising potential applications due to their transparency. However, their performance is strongly constrained due to the back contact, often referred to acting as a Schottky junction. In this work, we show that the current limitation due to a back Schottky junction can be responsible for the apparent photocurrent loss and suppression of the forward current, which deteriorates cell performance and leads to the S‐shapedJ‐Vcharacteristics, respectively. However, due to the non‐negligible photocurrent in the back Schottky diode and the current amplification effect of a transistor, cells with a reduced absorber thickness overall exhibit a relieved current suppression, resulting in a lightJ‐Vcurve closer to the one with an Ohmic back contact. Notably, a higher back interface recombination velocity is capable of increasing the forward current of the Schottky diode by recombination, which mitigates the limitation of current flow through the back Schottky junction and thus improves the cell performance. The results show strong implications that introducing high density defects at the back interface is favorable for CIGSe solar cells on TCOs, rather than employing point‐contact structures for interface passivation. This suggests a different path to improve ultrathin CIGSe solar cells on TCOs compared to the devices on Mo with an Ohmic back contact.

Impacts of COVID-19 Traffic Control Policy on Population Flows in Changsha

To investigate the impact of COVID-19 traffic control policies on population flow in Changsha, this paper divided the prevention and traffic control policies into different stages corresponding to the real-time epidemic situation in Changsha. Based on Baidu migration big data, the difference- in- difference model was used to identify different stages of traffic prevention and control policies and quantify the effect of prevention. With the traffic control policy implemented during COVID-19, the average inflow intensity of Changsha City decreased by 83.68%, the average outflow intensity decreased by 69.24% and the internal travel intensity respectively, decreased by 59.74%. After the end of the traffic control policies, the population flow intensity of Changsha City gradually rebounded, and the urban internal travel intensity basically recovered to the same level as in 2019. The results indicated the effectiveness of the traffic control policies on the limitation of population flow and epidemic spread. The results also provide reference for making effective prevention and control policies for the normalized COVID-19 epidemic situations. Copyright © 2021 by Science Press.

Void Fraction and Interfacial Friction in Vertical Circular Pipes with the Square Top End under Flooding Conditions

The objective of this study was to reduce the uncertainties of correlations for flow characteristics in vertical pipes under flooding at the top end. The void fraction α, pressure gradient dP/dz, and countercurrent flow limitation (CCFL) were previously measured with diameter D = 40 mm and working fluid of air and water. The wall friction and interfacial friction factors (fw and fi) were obtained based on the annular flow model, and CCFL and fw were evaluated in detail. Hence, attention was turned to detailed evaluations of α and fi. Liquid film thickness δ and interfacial friction factor fi for smooth film (SF) due to flooding at the top end were obtained using the previously derived fw correlation and existing dP/dz data with D = 20 to 50.8 mm and pressure P = 0.1 to 4.1 MPa, and empirical correlations for δ and fi were derived. The δ term was well expressed by a function of the liquid Reynolds number ReL, and the uncertainty of the δ correlation was ±0.0062 for α = 0.87 to 0.98. fi was expressed by a function of δ/L (where L is the Laplace length) or the Kutateladze parameter KG*, the dimensionless diameter D* (=D/L), and the density ratio of the gas and liquid phases ρG/ρL. The applicability of the derived correlations to conditions of D = 300 mm and P = 7 MPa was evaluated, and the fi correlation was modified based on fi values computed with the δ correlation. The drift-flux parameters for SF were also considered.

Transition flow occurrence on stepped channels

On a stepped channel, three distinct flow regimes, nappe, transition, and skimming, occur successively with increasing discharge. This work proposes a criterion of the transition flow occurrence: a critical slope of the channel exists between mild and steep slopes, and for mild slopes, air pocket disappearance and nappe parallel to channel slope are defined as the lower and upper limits of transition flow, whereas for steep slopes, the two phenomena oppositely represent the upper and lower limits. The analytical approaches based on the criterion demonstrate the critical slope of 30° and predict the lower and upper limits of transition flow. The experimental data verify the existence of the critical slope and its prediction accuracy, and indicate that the prediction of the lower and upper limits of transition flow works well for both mild (<30°) and steep (>30°) slopes. During stepped channel design, employing the critical slope can control the transition flow occurrence, therefore reducing the risks caused by structure vibration and excessive splashing.

Increased CaMKII-dependent pro-arrhythmic activity in a novel mouse model of obstructive sleep apnoea

Abstract Background Obstructive sleep apnoea (OSA) is frequently associated with atrial arrhythmias, but detailed mechanisms remain elusive. Most recently, we found an increased CaMKII-dependent pro-arrhythmic activity in patients with sleep apnoea. Since patients suffer from various confounding comorbidities, we have developed a novel mouse model of OSA by tongue enlargement. Purpose We tested if mice with OSA exhibit increased atrial CaMKII-dependent pro-arrhythmic activity. Methods Polytetrafluorethylene (PTFE) was injected into the tongue of 12 wild-type (WT) and 10 CaMKII knock-out (CKO) mice. 9 WT and 9 CKO mice were used as control without PTFE injection. Inspiratory flow limitations and apnoeas were monitored during murine sleep phases by whole-body plethysmography (Buxco). After eight weeks, isolated atrial cardiomyocytes were incubated with the Ca-sensitive dye FURA-2 AM for 15 min. Regular Ca transients were elicited by electrical field stimulation (1 Hz, 20 V for 4 ms) using epifluorescence microscopy. Pro-arrhythmic non-stimulated events were defined as deviations from diastolic Ca baseline between two stimulated Ca transients. Results Sonographic measurements revealed a significant increase in mean tongue diameter from (in mm) 3.7±0.1 to 5.1±0.1 after PTFE injection (n=23, p&amp;lt;0.0001). There was a significant correlation between magnitude of tongue diameter and frequency of apnoeas in OSA mice (p=0.046, r2=0.19, Fig. 1A). Interestingly, we observed a significantly increased frequency of pro-arrhythmic events of (in s–1) 0.06±0.01 in WT OSA mice compared to 0.02±0.01 in WT control mice (p=0.047, Fig. 1B). Similar results were observed at higher stimulation frequencies (2 and 4 Hz). There was a significant correlation of pro-arrhythmic events with inspiratory flow limitations (p=0.03, r2=0.24, Fig. 1C) and with the frequency of apnoeas by strong trend (p=0.06, r2=0.18). In contrast, no increase in atrial pro-arrhythmic events was observed in CKO mice after PTFE injection (for CKO mice after PTFE vs. CKO mice without PTFE, 0.03±0.01 s–1 vs. 0.03±0.01 s–1, p=0.89, Fig. 1B). Accordingly, the correlations between pro-arrhythmic events and both inspiratory flow limitations (p=0.36, r2=0.05, Fig. 1C) and apnoeas (p=0.82, r2=0.004) were completely abolished in CKO mice. Conclusion In a novel mouse model of obstructive sleep apnoea, atrial pro-arrhythmic activity was increased in a CaMKII-dependent fashion, which may have therapeutic implications. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Benedikt Schaner / Mr., this work is supported by a research grant of the German Cardiac Society (DGK); Stefan Wagner / Professor, was funded by DFG grants Figure 1