Hemodialysis does not impair ventricular functions over 2 years

We aimed to evaluate the long-term effect of hemodialysis (HD) treatment on left and right ventricular (LV and RV) functions in patients with end-stage renal disease. The study population consisted of 22 patients with newly diagnosed end-stage renal disease. Before an arteriovenous fistula was surgically created for HD, the patients were evaluated by echocardiography for systolic and diastolic functions. After the first HD session (mean 24.22 ± 2.14 months), the second echocardiographic evaluations were performed. Left ventricular and RV functions before and after long-term HD treatment were compared. The mean age was 55 ± 13 years and 10 (45%) of the patients were female. After long-term HD treatment, the isovolumic relaxation time was significantly decreased; however, the peak early (E) and late (A) diastolic mitral inflow velocities, E/A ratio, and deceleration time of E wave were not significantly different from the baseline measurements. Also, there was no significantly change in the early diastolic velocity (Ea) of the lateral mitral anulus and the E/Ea ratio. Pulmonary vein peak diastolic velocity, peak atrial reversal velocity, and peak atrial reversal velocity duration remained almost unchanged even though the pulmonary vein peak systolic velocity and the pulmonary vein peak systolic velocity/pulmonary vein peak diastolic velocity ratio were significantly lower after long-term HD treatment. In addition, LV systolic functions, LV diameters, LV mass index, left atrium size, and RV diastolic functions were not statistically different after long-term HD treatment. The myocardium is exposed to hemodynamic, metabolic, and neuro-humoral abnormalities during HD treatment; however, the long-term effects of HD on ventricular functions are not clearly known. The present study showed that the long-term effects of HD on LV and RV functions were insignificant in patients with end-stage renal disease. We have demonstrated that the LV and RV functions did not change significantly after long-term HD treatment. We suggest that this result may be due to regulated blood pressure levels of the patients, treatment of anemia and other metabolic disorders during the HD period and the prevention of weight gain and hypervolemia.     

Mechanisms of transmurally varying myocyte electromechanics in an integrated computational model

The mechanical properties of myocardium vary across the transmural aspect of the left ventricular wall. Some of these functional heterogeneities may be related to differences in excitation-contraction coupling characteristics that have been observed in cells isolated from the epicardial, mid-myocardial and endocardial regions of the left ventricle of many species, including canine. Integrative models of coupled myocyte electromechanics are reviewed and used here to investigate sources of heterogeneous electromechanical behaviour in these cells. The simulations (i) illustrate a previously unrecognized role of the transient outward potassium current in mechanical function and (ii) suggest that there may also exist additional heterogeneities affecting crossbridge cycling rates in cells from different transmural regions.     

Identification of ultrasound contrast agent dilution systems for ejection fraction measurements

Left ventricular ejection fraction is an important cardiac-efficiency measure. Standard estimations are based on geometric analysis and modeling; they require time and experienced cardiologists. Alternative methods make use of indicator dilutions, but they are invasive due to the need for catheterization. This study presents a new minimally invasive indicator dilution technique for ejection fraction quantification. It is based on a peripheral injection of an ultrasound contrast agent bolus. Left atrium and left ventricle acoustic intensities are recorded versus time by transthoracic echocardiography. The measured curves are corrected for attenuation distortion and processed by an adaptive Wiener deconvolution algorithm for the estimation of the left ventricle impulse response, which is interpolated by a monocompartment exponential model for the ejection fraction assessment. This technique measures forward ejection fraction, which excludes regurgitant volumes. The feasibility of the method was tested on a group of 20 patients with left ventricular ejection fractions going from 10% to 70%. The results are promising and show a 0.93 correlation coefficient with echographic bi-plane ejection fraction measurements. A more extensive validation as well as an investigation on the method applicability for valve insufficiency and right ventricular ejection fraction quantification will be an object of future study.     

A new multi-scale simulation model of the circulation: from cells to system

We developed a comprehensive cell model that simulates the sequential cellular events from membrane excitation to contraction in the human ventricle. By combining this ventricular cell model with a lumped circulation model, we examined how blood pressure dynamics in the ventricle and aorta are related to the cellular processes. To convert cell contraction into ventricular pressure using Laplace's law, we introduced a simple geometric model of a ventricle: one shaped like a thin-walled hemisphere. The force of contraction of a single cell induces tension in the hemispheric ventricular wall, which generates the ventricular and aortic pressures in the lumped circulation model. The time courses of the hemodynamic properties, as well as the volume-pressure trajectory of the left ventricle, were well reproduced. Our multi-scale cardiovascular model, which covers from cardiac cells to the circulatory system, simulates the typical characteristics of heart mechanics, such as the pressure-volume relationship, stroke volume and the effect of the increased maximum free calcium concentration on cardiovascular hemodynamics. To test the cell-circulation coupling characteristics of the model, we simulated the effects of a decrease in L-type calcium channel conductance (cell level) on left ventricular pressure (system level). The variation due to different pacing frequencies for myocyte excitation was also investigated to assess the effects of heart rate on cardiac cells and the circulatory system.     

Effect of pharmacological suppression of secondary hyperparathyroidism on cardiovascular hemodynamics in predialysis CKD patients: A preliminary observation

Cardiovascular events are the principal cause of mortality in patients with chronic kidney disease (CKD). Secondary hyperparathyroidism (SHPT), a common complication of CKD, contributes to cardiac dysfunction. This study is an attempt to demonstrate the effects of parathyroid hormone suppression with oral calcitriol on cardiovascular hemodynamics. Twenty predialysis CKD patients with SHPT were given calcitriol therapy for 12 weeks. Ten similar patients received placebo. Echocardiographic assessment of cardiac function was performed at baseline and after 12 weeks of treatment. Calcitriol therapy effectively suppressed SHPT. Baseline left ventricular (LV) end diastolic diameter and LV end systolic diameter were 4.86+/-0.48 and 2.86+/-0.33 cm, and the mean FS was 41.02+/-4.79%. Left ventricular end systolic and end diastolic volumes were normal (42.30+/-9.07 and 91.40+/-19.68 mL). The ejection fraction was slightly reduced (53.54+/-3.57%). Pretreatment Doppler indices including E velocity (0.816+/-0.087 m/s), A velocity (0.696+/-0.089 m/s), and E/A ratio (1.193+/-0.210) were significantly impaired. After 12 weeks of calcitriol therapy, there was no significant change in the LV dimensions or ejection fraction, but there was a significant improvement in the diastolic parameters, namely the A velocity (0.680+/-0.084) and E/A ratio (1.238+/-0.180). Secondary hyperparathyroidism is an important factor in the pathogenesis of cardiovascular complications in CKD. There is evidence to support that correction of hyperparathyroidism can improve the systolic dysfunction seen in advanced kidney disease. This study shows that diastolic dysfunction seen in predialysis CKD patients may also be possibly improved with calcitriol therapy.     

Regional ejection fraction and regional area strain for left ventricular function assessment in male patients after first-time myocardial infarction

In this work, we present a method to assess left ventricle (LV) regional function from cardiac magnetic resonance (CMR) imaging based on the regional ejection fraction (REF) and regional area strain (RAS). CMR scans were performed for 30 patients after first-time myocardial infarction (MI) and nine age- and sex-matched healthy volunteers. The CMR images were processed to reconstruct three-dimensional LV geometry, and the REF and RAS in a 16-segment model were computed using our proposed methodology. The method of computing the REF was tested and shown to be robust against variation in user input. Furthermore, analysis of data was feasible in all patients and healthy volunteers without any exclusions. The REF correlated well with the RAS in a nonlinear manner (quadratic fit—R² = 0.88). In patients after first-time MI, the REF and RAS were significantly reduced across all 16 segments (REF: p < 0.05; RAS: p < 0.01). Moreover, the REF and RAS significantly decreased with the extent of transmural scar obtained from late gadolinium-enhanced CMR images. In addition, we show that the REF and RAS can be used to identify regions with compromised function in the patients with preserved global ejection fraction with reasonable accuracy (more than 78%). These preliminary results confirmed the validity of our approach for accurate analysis of LV regional function. Our approach potentially offers physicians new insights into the local characteristics of the myocardial mechanics after a MI.     

Relationship between erythropoietin resistance index and left ventricular mass and function and cardiovascular events in patients on chronic hemodialysis

The response to erythropoietin (EPO) treatment varies considerably in individual patients on chronic hemodialysis. The EPO resistance index (ERI) has been considered useful to assess the EPO resistance and can be easily calculated in the clinic. The aim of this study was to investigate the association between ERI and left ventricular mass (LVM) and function and to determine whether ERI was associated with cardiovascular events in patients on hemodialysis. This study was designed prospectively. Clinical, laboratory, and echocardiographic variables were assessed in 72 patients on hemodialysis. The ERI was determined as the weekly weight-adjusted dose of EPO (U/kg/week) divided by hemoglobin concentration (g/dL). Patients were divided into three groups by tertiles of ERI. Patients with higher tertiles of ERI had a higher LVM index and lower LV ejection fraction compared with those with lower tertiles of ERI (P = 0.019 and P = 0.030, respectively). The median follow-up period was 53 months. The Kaplan-Meier plot showed increased frequency of cardiovascular events in patients with higher tertiles of ERI, compared with those with lower tertiles of ERI (P = 0.011, log-rank test). The multivariate Cox proportional hazard models showed that the ERI was the significant independent predictor of cardiovascular events (HR 3.00, 95% CI, 1.04-8.62, P = 0.042). Our data show that ERI was related with LVM index, LV systolic function and cardiovascular events in patients with hemodialysis. By monitoring of ERI, early identification of the EPO resistance may be helpful to predict the cardiovascular risk in hemodialysis patients.     

Lethal cardiac arrhythmia during central venous catheterization in a uremic patient: A case report and review of the literature

Double‐lumen central venous catheter (CVC) is a rapid access technique for hemodialysis (HD) when an arteriovenous fistula or graft is not available. A variety of procedure‐related complications have been reported, such as infection and pneumothorax, but serious cardiac complications are relatively less mentioned. We report a uremic woman with preexisting left bundle branch block who required emergent HD and received jugular double‐lumen CVC insertion, which was complicated by short‐duration ventricular tachycardia followed by complete atrio‐ventricular block and bradycardia. Pharmacological management did not reverse heart rate and rhythm. External pacing was not applied because she remained hemodynamically stable in the course of HD. Heart rate returned to sinus rhythm with left bundle branch block 4 hours later and did not recur through the whole admission period. We speculate that the transient arrhythmia might have been induced by mechanical contact with the ventricular wall during the procedure with the guided metallic wire. In conclusion, physicians responsible for CVC catheterization should pay more attention to patients with preexisting cardiac arrhythmia to prevent such technical mistakes from transpiring.     

Prospective ECG-gated mouse cardiac imaging with a 34-MHz annular array transducer

Prospective imaging with electrocardiogram (ECG) and respiratory gating presents an imaging application that leverages the improved image quality of high-frequency (>20 MHz) annular arrays without the need for rapid mechanical motion. The limitation of prospective imaging is that the object being imaged must have a periodically stable motion. The present study investigated the implementation of prospective imaging with a 34 MHz annular-array scan system to image the mouse heart at high effective frame rates, >200 frames/s (fps). M-mode data for all transmit-to-receive pairs were acquired at a series of spatial locations using ECG and respiratory gating, and the data were then synthetically focused in postprocessing. The pulse-repetition frequency of the M-mode data determined the effective frame rate of the final B-mode image sequence. The hearts of adult mice were prospectively imaged and compared with retrospective data acquired with a commercial ultrasonic biomicroscope (UBM). The annulararray data were acquired at an effective frame rate of 500 fps spanning 0.5 s, and the UBM data were acquired at 1000 fps spanning 0.15 s. The resulting images showed that multiple heart cycles could be clearly resolved using prospective imaging and that synthetic focusing improved image resolution and SNR of the right ventricle, interventricular septum, posterior edge of the left ventricle (LV), and papillary muscles of the LV versus fixed-focused imaging and the retrospective imaging of the UBM machine.     

Synergy between shear-induced migration and secondary flows on red blood cells transport in arteries: considerations on oxygen transport

Shear-induced migration of red blood cells (RBCs) is a well-known phenomenon characterizing blood flow in the small vessels (micrometre to millimetre size) of the cardiovascular system. In large vessels, like the abdominal aorta and the carotid artery (millimetre to centimetre size), the extent of this migration and its interaction with secondary flows has not been fully elucidated. RBC migration exerts its influence primarily on platelet concentration, oxygen transport and oxygen availability at the luminal surface, which could influence vessel wall disease processes in and adjacent to the intima. Phillips'' shear-induced particle migration model, coupled to the Quemada viscosity model, was employed to simulate the macroscopic behaviour of RBCs in four patient-specific geometries: a normal abdominal aorta, an abdominal aortic aneurysm (AAA), a normal carotid bifurcation and a stenotic carotid bifurcation. Simulations show a migration of RBCs from the near-wall region with a lowering of wall haematocrit (volume fraction of RBCs) on the posterior side of the normal aorta and on the lateral-external side of the iliac arteries. A marked migration is observed on the outer wall of the carotid sinus, along the common carotid artery and in the carotid stenosis. No significant migration is observed in the AAA. The spatial and temporal patterns of wall haematocrit are correlated with the near-wall shear layer and with the secondary flows induced by the vessel curvature. In particular, secondary flows accentuate the initial lowering in RBC near-wall concentration by convecting RBCs from the inner curvature side to the outer curvature side. The results reinforce data in literature showing a decrease in oxygen partial pressure on the inner curvature wall of the carotid sinus induced by the presence of secondary flows. The lowering of wall haematocrit is postulated to induce a decrease in oxygen availability at the luminal surface through a diminished concentration of oxyhaemoglobin, hence contributing, with the reported lowered oxygen partial pressure, to local hypoxia.     

Timing HIV infection with a simple and accurate population viral dynamics model

Clinical trials for HIV prevention can require knowledge of infection times to subsequently determine protective drug levels. Yet, infection timing is difficult when study visits are sparse. Using population nonlinear mixed-effects (pNLME) statistical inference and viral loads from 46 RV217 study participants, we developed a relatively simple HIV primary infection model that achieved an excellent fit to all data. We also discovered that Aptima assay values from the study strongly correlated with viral loads, enabling imputation of very early viral loads for 28/46 participants. Estimated times between infecting exposures and first positives were generally longer than prior estimates (average of two weeks) and were robust to missing viral upslope data. On simulated data, we found that tighter sampling before diagnosis improved estimation more than tighter sampling after diagnosis. Sampling weekly before and monthly after diagnosis was a pragmatic design for good timing accuracy. Our pNLME timing approach is widely applicable to other infections with existing mathematical models. The present model could be used to simulate future HIV trials and may help estimate protective thresholds from the recently completed antibody-mediated prevention trials.     

Noninvasive estimation of dynamic pressures in vitro and in vivo using the subharmonic response from microbubbles

The purpose of this study was to develop and validate a noninvasive pressure estimation technique based on subharmonic emissions from a commercially available ultrasound contrast agent and scanner, unlike other studies that have either adopted a single-element transducer approach and/ or use of in-house contrast agents. Ambient pressures were varied in a closed-loop flow system between 0 and 120 mmHg and were recorded by a solid-state pressure catheter as the reference standard. Simultaneously, the ultrasound scanner was operated in pulse inversion mode transmitting at 2.5 MHz, and the unprocessed RF data were captured at different incident acoustic pressures (from 76 to 897 kPa). The subharmonic data for each pulse were extracted using band-pass filtering with averaging, and subsequently processed to eliminate noise. The incident acoustic pressure most sensitive to ambient pressure fluctuations was determined, and then the ambient pressure was tracked over 20 s. In vivo validation of this technique was performed in the left ventricle (LV) of 2 canines. In vitro, the subharmonic signal could track ambient pressure values with r(2) = 0.922 (p < 0.001), whereas in vivo, the subharmonic signal tracked the LV pressures with r(2) > 0.790 (p < 0.001) showing a maximum error of 2.84 mmHg compared with the reference standard. In conclusion, a subharmonic ultrasound-based pressure estimation technique, which can accurately track left ventricular pressures, has been established.     

A fully-coupled fluid-structure interaction simulation of cerebral aneurysms

This paper presents a computational vascular fluid-structure interaction (FSI) methodology and its application to patient-specific aneurysm models of the middle cerebral artery bifurcation. A fully coupled fluid-structural simulation approach is reviewed, and main aspects of mesh generation in support of patient-specific vascular FSI analyses are presented. Quantities of hemodynamic interest such as wall shear stress and wall tension are studied to examine the relevance of FSI modeling as compared to the rigid arterial wall assumption. We demonstrate the importance of including the flexible wall modeling in vascular blood flow simulations by performing a comparison study that involves four patient-specific models of cerebral aneurysms varying in shape and size.     

Flow induced by ependymal cilia dominates near-wall cerebrospinal fluid dynamics in the lateral ventricles

While there is growing experimental evidence that cerebrospinal fluid (CSF) flow induced by the beating of ependymal cilia is an important factor for neuronal guidance, the respective contribution of vascular pulsation-driven macroscale oscillatory CSF flow remains unclear. This work uses computational fluid dynamics to elucidate the interplay between macroscale and cilia-induced CSF flows and their relative impact on near-wall dynamics. Physiological macroscale CSF dynamics are simulated in the ventricular space using subject-specific anatomy, wall motion and choroid plexus pulsations derived from magnetic resonance imaging. Near-wall flow is quantified in two subdomains selected from the right lateral ventricle, for which dynamic boundary conditions are extracted from the macroscale simulations. When cilia are neglected, CSF pulsation leads to periodic flow reversals along the ventricular surface, resulting in close to zero time-averaged force on the ventricle wall. The cilia promote more aligned wall shear stresses that are on average two orders of magnitude larger compared with those produced by macroscopic pulsatile flow. These findings indicate that CSF flow-mediated neuronal guidance is likely to be dominated by the action of the ependymal cilia in the lateral ventricles, whereas CSF dynamics in the centre regions of the ventricles is driven predominantly by wall motion and choroid plexus pulsation.     

Left ventricular mechanical dyssynchrony in patients with different stages of chronic kidney disease and the effects of hemodialysis

Left ventricular (LV) dyssynchrony is a known cause of mortality in patients with heart failure and may possibly play a similar role in patients with chronic kidney disease (CKD) in whom sudden death is one of the most common and as yet not fully explained cause of death. LV synchronicity and its relationship with increased volume load and various biomarkers was analyzed in 145 patients including 53 patients with CKD stages 3 and 4 and in 92 CKD stage 5 patients undergoing hemodialysis (HD) or peritoneal dialysis (PD) using color tissue Doppler imaging and tissue synchronization imaging. The HD patients were evaluated both before and after a single HD session. LV dyssynchrony was defined as a regional difference in time to peak systolic myocardial velocity, between 12 LV segments > 105 milliseconds. LV dyssynchrony was present in 54% of the patients with no difference between CKD 3 and 4 (58%), HD (48%), and PD (51%). LV dyssynchrony was independently associated with LV mass index and increased estimation of LV end‐diastolic pressure. A single HD session resulted in significant changes in LV synchronicity variables—with improvement in 50% of the patients—especially in patients with higher myocardial systolic velocities and lower LV mass index. Abnormalities in LV synchronicity are highly prevalent in CKD patients already prior to dialysis treatment and are associated with LV hypertrophy, LV dysfunction and load conditions, underlining the importance of volume status for LV synchronicity in CKD patients.     

Colour-Doppler echocardiography flow field velocity reconstruction using a streamfunction–vorticity formulation

We introduce a new method (Doppler Velocity Reconstruction or DoVeR), for reconstructing two-component velocity fields from colour Doppler scans. DoVeR employs the streamfunction–vorticity equation, which satisfies mass conservation while accurately approximating the flow rate of rotation. We validated DoVeR using artificial colour Doppler images generated from computational fluid dynamics models of left ventricle (LV) flow. We compare DoVeR against the conventional intraventricular vector flow mapping (iVFM_1D) and reformulated iVFM (iVFM_2D). LV model error analysis showed that DoVeR is more robust to noise and probe placement, with noise RMS errors (nRMSE) between 3.81% and 6.67%, while the iVFM methods delivered 4.16–24.17% for iVFM_1D and 4.06–400.21% for iVFM_2D. We test the DoVeR and iVFM methods using in vivo mouse LV ultrasound scans. DoVeR yielded more haemodynamically accurate reconstructions, suggesting that it can provide a more reliable approach for robust quantification of cardiac flow.     

Thermally induced birefringence in nonsymmetrically pumped laser rods and its implications for attainment of good beam quality in high-power, radially polarized lasers

The ability to generate and then amplify radially polarized light opens up the possibility of achieving very high-power, near diffraction-limited beams from rod-based solid-state lasers. Residual bifocusing rapidly degrades beam quality. Residual bifocusing results from nonradially symmetric pump distributions. We analyze how a nonradially symmetric pump distribution induces a nonradially symmetric stress map. This manifests itself as nonradially symmetric birefringence, and as depolarization to radially/azimuthally polarized beams (or as deterioration in birefringence compensated linearly polarized lasers). Here we analytically describe the birefringence terms of a nonradially symmetric strain map. The model results are supported by radial-depolarization measurements in our 2 kW Nd:YAG pump chambers. For the current level of depolarization, beam quality degradation per rod is DeltaM(2)=4 because of bifocusing alone. The degradation per rod can be reduced substantially by improving pump uniformity.     

叶轮时序对多级泵振动特性影响的试验测试

叶轮时序效应对于旋转机械的振动性能有着重要的影响。以实验测试研究了叶轮时序效应对一台五级离心泵振动特性的影响。采用正交设计方法设计了8个实验方案,在多级泵5个不同位置进行振动特性的测量,包括进口轴向、进口出口的水平和垂直方向。结果表明,时序效应对多级泵水平方向上振动的影响大于垂直方向上振动的影响,所有测点的振动谐频都位于1×fn、2×fn、3×fn和4×fn。叶轮时序效应对每个谐频幅值都存在重要的影响,在不同的方案下,1×fn、2×fn、3×fn和4×fn上幅值的最大变化可达17.7%、10.0%、33.2%和47.4%。对比各方案,发现调整第二和第三泵级叶轮的时序位置,可以获得较好的整泵振动特性。