Increase In Blood Flow Rate Research Articles

Impact on change in serum beta 2 microglobulin by combination therapy of peritoneal dialysis and hemodialysis: a 12-month preliminary observational study

BackgroundIn the Japanese guidelines on combination peritoneal dialysis (PD) and hemodialysis (HD) therapy, patients with serum beta 2 microglobulin (β2MG) levels less than 30 mg/L are recommended. And PD patients with β2MG more than 30 mg/L are considered to transfer to the PD + HD combination therapy. However, the resultant changes in serum β2MG levels by the introduction of PD + HD combination therapy and the factors influencing the change have not clearly elucidated.MethodsWe retrospectively studied 11 PD patients (mean age 56.4 ± 12.9 years, 10 males) with baseline β2MG levels > 30 mg/L with respect to changes in β2MG and its related factors for 12 months after the introduction of combination therapy of PD plus once a week HD (4 h) using a high-performance dialyzer. Laboratory data including hemoglobin, albumin, C-reactive protein, blood urea nitrogen, creatinine, and the patients’ demographic profiles, and HD-related factors, such as Kt/V and blood flow rate, were assessed.ResultsSerum β2MG levels decreased statistically significantly after the introduction of combination therapy: from 36.7 ± 6.7 mg/L at 0 months, to 33.4 ± 6.1 mg/L at 3 months (p = 0.030, compared to baseline), 32.9 ± 4.5 mg/L at 6 months (p = 0.009), and 33.3 ± 5.3 mg/L at 12 months (p = 0.023), respectively. However, only 27–36% patients achieved target β2MG levels of < 30 mg/L during the observation period. Regarding influencing factors, serum albumin levels, blood flow rates of HD, residual renal function and baseline β2MG were associated with a decrease in serum β2MG levels on univariate analysis. In multivariate analysis, serum albumin at 3 and 12 months correlated significantly with Δβ2MG (β = − 0.990, p = 0.032 at 3 months, β = − 0.551, p = 0.033 at 12 months). Urine volume at 12 months correlated significantly with Δβ2MG (β = 0.507, p = 0.019).ConclusionsCombination therapy of PD and HD might reduce serum β2MG levels, but with marginal efficacy. Our preliminary data indicate that the combination therapy of PD and once weekly HD is not sufficient to significantly decrease serum β2MG levels. Additional HD prescriptions, such as increase in blood flow rate and hemodiafiltration, need to be tested in order to improve β2MG levels in these patients.

Patient-specific computational haemodynamics associated with the surgical creation of an arteriovenous fistula

Despite arteriovenous fistulae (AVF) being the preferred vascular access for haemodialysis, high primary failure rates (30-70%) and low one-year patency rates (40-70%) hamper their use. Furthermore, AVF creation has been associated with haemodynamic changes causing maladaptive cardiac remodelling leading to cardiovascular (CV) complications. In this study, we present a new workflow for characterising the haemodynamic profile prior to and following surgical creation of a successful left radiocephalic AVF in a 20-year-old end-stage kidney disease patient. The reconstructed vasculature was generated using multiple ferumoxytol-enhanced magnetic resonance angiography (FeMRA) datasets. Computational fluid dynamics (CFD) simulations utilising a scale-resolving turbulence model were completed to investigate the changes in the proximal haemodynamics following AVF creation, in addition to the post-AVF juxta-anastomosis flow patterns, which is impractical to obtain in-vivo. Following AVF creation, a significant 2-3-fold increase in blood flow rate was induced downstream of the left subclavian artery. This was validated through comparison with post-AVF patient-specific phase-contrast data. Proximal to the anastomosis, the increased flow rate yielded an increase in time-averaged wall shear stress (WSS), which is a key marker of adaptive vascular remodelling. In the juxta-anastomosis region, the success of the AVF was discussed with respect to the National Kidney Foundation's vascular access guidelines, where the patient-specific AVF met the flow rate and geometry criterion. The AVF venous diameter exceeded 6mm and the venous flow rate surpassed 600mL/min. This workflow may potentially be significant clinically when applied to multi-patient cohorts, with population-wide patient-specific conclusions being ascertained for the haemodynamic assessment of AVFs and improved surgical planning.

The Natural-Mineral-Based Novel Nanomaterial IFMC Increases Intravascular Nitric Oxide without Its Intake: Implications for COVID-19 and beyond.

There are currently no promising therapy strategies for either the treatment or prevention of novel coronavirus disease 2019 (COVID-19), despite the urgent need. In addition to respiratory diseases, vascular complications are rapidly emerging as a key threat of COVID-19. Existing nitric oxide (NO) therapies have been shown to improve the vascular system; however, they have different limitations in terms of safety, usability and availability. In light of this, we hypothesise that a natural-mineral-based novel nanomaterial, which was developed based on NO therapy, might be a viable strategy for the treatment and prevention of COVID-19. The present study examined if it could induce an increase of intravascular NO, vasodilation and the consequent increase of blood flow rate and temperature in a living body. The intravascular NO concentration in the hepatic portal of rats was increased by 0.17 nM over 35.2 s on average after its application. An ultrasonic Doppler flow meter showed significant increases in the blood flow rate and vessel diameter, but no difference in the blood flow velocity. These were corroborated by measurements of human hand surface temperature. To our knowledge, this result is the first evidence where an increase of intravascular NO and vasodilation were induced by bringing a natural-mineral-based nanomaterial into contact with or close to a living body. The precise mechanisms remain a matter for further investigation; however, we may assume that endothelial NO synthase, haemoglobin and endothelium-derived hyperpolarising factor are deeply involved in the increase of intravascular NO.

P1423INCREASED BLOOD FLOW RATE IN HIGH-FLUX HAEMODIALYSIS - IS IT RELEVANT FOR PHOSPHORUS REMOVAL IN HAEMODIALYSIS PATIENTS?

Abstract Background and Aims High-flux haemodialysis (HD), beside other uremic solutes harmful for patients, controls the level of phosphorus, major factor for HD-related morbidity and mortality. First line in phosphorus control in HD patients is dietary phosphorus intake reduction, whereas its’ removal is undervalued by hemodialysis. The primary objective was to analyse whether change in the rate of blood flow is relevant in phosphorus removal in HD patients. Second objective was to evaluate other variables impacted by higher blood flow rates. Method Retrospective study was conducted enrolling 80 patients from a single center in a period of 12 months. In the first six months, all patients were on lower blood flow rate (LBFR group) than the same patient group was switched to a higher blood flow rate in the following six months (HBFR group). Demographic, clinical and laboratory variables were collected and intra/inter-patient group analysis was performed. Results Forty-seven patients were male, and 41.3% were female. Mean age of the study population was 61.2±13.47 years (males 60.3±13.38, females 62.4±13.68). Mean dialysis vintage was 63.31±66.57 months. The average real blood flow rate in LBFR group was 290.75±19.65 ml/min (median 285.34 ml/min), 344.87±9.12 ml/min in HBFR group (median 339 ml/min), p=0.0002. The level of phosphorus in LBFR group was 1.52±0.03 mmol/L, and 1.45±0.04 in HBFR group, p=0.007. Other variables that significantly showed improvement following the increase of blood flow rate were eKT/V (p=0.0006), urea clearance (p=0.02) and transferrin saturation (p=0.04). The level of post-HD urea (p=0.02) and body surface area (p=0.04) were decreased. Weekly EPO dosage decrease in HBFR group (p=0.02) was not correlated with increased iron sucrose administration (LBFR group 59.99±36.18 mg/wk, HBFR group 65.8±28.7, p=0.45). There were no significant changes related to cardiac function; systolic (p=0.44) and diastolic pressure (p=0.36), mean arterial (p=0.43) and pulse pressure (p=0.26) remained in reference range. Also, the average dose of calcium-based phosphate binders did not change significantly (p=0.34). Conclusion This study showed that increased blood flow rate in HD patients reduces phosphorus and EPO consumption, improves urea clearance without significant impact on cardiac function and calcium overload with calcium-based phosphate binders.

Changes in functional, anatomical and optical parameters of the eye in children with habitually excessive accommodation stress and pseudomyopia after regular badminton playing

Purpose. To study the state of refraction, accommodation, and blood flow in eye vessels of children with habitually excessive accommodation stress (HEAS) and pseudomyopia practicing badminton.Material and methods. The study involved 11 patients (20 eyes) aged 7 to 11 years (average M±SD: 9.24 ± 1.06 years) with pseudomyopia and HEAS: 4 patients with myopia (7 eyes), 3 children with hyperopia (6 eyes), 4 children with emmetropia (7 eyes) before they started practicing badminton and after playing it for a certain time. All patients were tested for visual acuity, subjective and objective accommodation, optical biometry, aberrometry, velocity of blood flow in eye vessels, and choroidal thickness.Results. After 1 year of regular badminton workout, the subjects revealed a 0.92 ± 0.82 D weakening of manifest refraction, a decrease in accommodation tone by 0.85 ± 0.77 D, an increase in blood flow rate in ophthalmic artery and the central retinal artery, an increase in positive spherical aberration, a decrease in aberrations associated with mismatch and irregularity ofoptical system elements (tilt, trefoil, coma), which indirectly indicates a strengthening of the ligamentous apparatus of the lens.Conclusion. Practicing sports (badminton) contributes to the elimination of pseudomyopia, improvement of uncorrected visual acuity, accommodative ability, and ophthalmic hemodynamics indicators.

Assessment of an Arterial Stiffness to Demonstrate AVF Performance: Modelling Approach

Arteriovenous fistula (AVF) defined as shunting in the arterial system and the venous conduit is a preferred vascular access used in haemodialysis. The AVF provide a sufficient increase in blood flow rates for effective dialysis. However maintaining AVF patency become the greatest challenge for dialysis patient. Complications arise from this includes stenosis, aneurism and thrombosis. In previous studies, several methods are used to evaluate the performance of AVF. This study will focus on the assessment of arterial stiffness to demonstrate the performance of a side-to-side AVF. The condition of arterial stiffness which alter haemodynamic of AVF, in fact, will affect its performance and functionality. To gain insight and understanding for the haemodynamic condition, a healthy AVF (without arterial stiffening) has been modelled in the computational fluid dynamic (CFD) framework. The aim of this project is therefore to develop a modelling approach, suitable for the analyses of blood flow field to predict the performance and patency of AVF. A 3D CFD method is proposed to analysis flow field or haemodynamic in terms of blood flow velocity, blood pressure and wall shear stress (WSS) along the AVF. A laminar flow was introduced for the simulation of healthy AVF. Correlations in these haemodynamic parameters to assess the vascular failure supports hypothesis suggesting flow field as predicator for AVF performance. Haemodynamic effects lead to AVF failure were determined. Significant flow disturbances with abnormally high or low WSS obtained from the simulation is used as a primary indicator.

Evaluation of hemodynamic impact of absorbable sutures in native arteriovenous fistulas: A retrospective study.

One of the major causes of arteriovenous fistula failure is the venous stenosis due to aggressive neointimal hyperplasia. The aim of the study was to assess the arteriovenous fistula maturation comparing absorbable sutures and non-absorbable ones in native vessels. Surgeries performed during a period of 24 months by a single team of expert surgeons were evaluated. Surgeries that met the inclusion criteria, namely, age ⩾ 18 years and radio-cephalic arteriovenous fistula, were considered. According to type of suture, patients were classified as Max group (absorbable suture) and Prol group (non-absorbable). Data pertaining to 70 patients were collected; 51% were men and the mean age was 73 ± 12 years. In Max group, an increasing blood flow was observed during the first 4 weeks without post-operative complications. In Prol group, six patients had thrombosis that resulted in vascular access failure. After the first week, the duplex Doppler ultrasound of both groups showed a regular arteriovenous fistula maturation, with an increase of blood flow rate. Although pre-operative post-tourniquet mean vein diameters of Max group were not adequate, the mean vein diameter and mean blood flow rate increased after 4 weeks, respectively. On the contrary, in Prol group, mean vein diameters and blood flow rate decreased. The maturation of arteriovenous fistula and its functional performance were not altered by the type of suture (absorbable/non-absorbable). Absorbable sutures were associated with good results considering arteriovenous fistula maturation.

Changes of endothelial function and intracardiac hemodynamics during implantation of different types of pacemakers

Aim. To determine the dynamics of endothelial function and intracardiac hemodynamics during implantation of different types of pacemakers. Material and methods. The study involved 61 patients, 29 of them were implanted with single-chamber pacemaker (the first group), 32 — two-chamber pacemaker (second group) with sick sinus syndrome (SSS), as well as patients with 2-3 degrees AV conduction disorder. Test with endothelium-dependent vasodilation of the brachial artery was performed using the standard technique and the velocity parameters of blood flow were determined. Parameters of intracardiac hemodynamics and left atrial (LA) function were determined. These studies were conducted in patients initially upon admission to the hospital and 2 months later implantation of pacemaker. Results. Endothelium-dependent vasodilation significantly deteriorated in patients with single-chamber pacemaker which initially was 6,1 [2,74;9,815]% and in 2 months decreased to 5,4 [2,37;7,55]% (p=0,05). There was a tendency to deterioration of left ventricular (LV) contractile function accompanied by a decrease in ejection fraction (EF) to 55,04 [49,04;68,72]%, and decrease emptying fraction of LA to 37,36 [31,67;52,85]%. There was a tendency to increase the volume index of LA which indicates an increasing overload of the volume and pressure of LA. There was a significant increase in the degree of endothelium-dependent vasodilation in patients of the second group initially compiling a 3,25 [2,15;6,61]% and then reaches 6,15 [2,75;8,97]% 2 months after surgery (p <0,04). There was no overload in the volume and pressure of LA and improved indirect signs of LV compliance parameters (growth of end-systolic dimension and volume) and decreased LV EF to 53,23 [44,1;69,95]%. In patients in the first group there was a tendency to increase peripheral resistance to 1227 [1065;1318] dyne x cm -5 x sec, accompanied by a significant decrease in blood flow rate. In the second group there was a tendency to reduce peripheral resistance to 1215 [1136;1391] dyne x cm -5 x sec and a significant increase in blood flow rate. There was a significant correlation between the systole LA dimension and total peripheral resistance in patients with VVI stimulation (r=0,78, p=0,0022), which indicates an increase in total peripheral resistance with a change in blood flow from LA to LV and a decrease in cardiac output. Conclusion. Endothelial function deteriorates with single-chamber stimulation and improves with two-chamber stimulation. These changes are based on shear stress and nitric oxide endothelium secretion the changes of which depend on the characteristics of central and peripheral hemodynamics.

Pathogenetic role of the autonomic nervous system in arterial hypotension cardiac remodeling in young women

Aim. To study the features of cardiac remodeling on condition of the autonomic nervous system (ANS) in young women with idiopathic arterial hypotension (IAH).Material and methods. A comparative analysis of the echocardiography data in women with IAH aged 18-25 years with a predominance of sympathetic (n=150) and parasympathetic (n=60) parts of the ANS was performed. The level of systolic blood pressure ≤98 mm Hg worked as the criterion of IAH. The activity of the ANS was evaluated by the I. Kérdö index.Results. It has been shown that women with IAH with sympathicotonia are characterized by a significant decrease in the structural parameters of the heart: the size of all chambers and the aortic ostium, contractile function decrease and a slower relaxation of the left ventricle (LV). Acceleration of intracardiac hemodynamics was observed: an increase in blood flow rates and pressure gradients on the mitral, tricuspid and pulmonary artery valves, an increase in the rates of early and late diastolic LV filling. Changes in early LV diastole are associated with an increase of pressure in the left atrium. We identified a restrictive type of diastolic dysfunction in women with parasympathicotonia.Conclusion. Sympathicotonia and parasympathicotonia in young women with IAH are associated with different heart remodeling variants. Cardiac hypotrophy, decrease of contractile function and impaired LV relaxation during hypotension are associated with low sympathetic activity against the background of parasympathicotonia. The restrictive type of diastolic dysfunction during hypotension is associated with parasympathicotonia. Use of cholinolytics and anticholinesterase reactivators are the potential way of correction of ANS dysfunction, IAH regression and cardiac remodeling.

Influence Of Various Forms Of Pressure Stimulation On Skeletal Muscle Condition

PURPOSE: We investigated the effect of various forms of pressure on skeletal muscle condition with muscle temperature, muscle stiffness, oxygen saturation and B-mode ultrasound. METHODS: Six young male students (age 22.7 ±1.8 y, height 177.1 ± 3.9 cm, weight 69.7 ± 2.1 kg) completed the following intervention protocols in a randomized order on separate days: non-stimulation (C: control condition), Low pressure stimulation (LP), and High pressure stimulation (HP) at the rectus femoral. Subjects kept rest on bed. After the various forms of pressure stimulation or control intervention, muscle temperature, oxygenated saturation, muscle stiffness, B-mode ultrasound. The indicators of muscle condition were measured pre-stimulation, immediately post, 10, 20, and 30 minutes afterward. RESULTS: The muscle temperature increase to 10 minute in the HP, and a significant difference was recognized as compared with the C and LP (p<0.01). However, no significant difference was observed after 30 minutes. Oxygen saturation showed that the HP tended to be high after stimulation. Muscle stiffness decreased in both HP and LP immediately after stimulation, and the HP showed to return to baseline after 30 minutes from immediately after stimulation, and no significant difference was observed. The LP showed to maintain and a significant difference was observed as compared with the C (p<0.01). B-mode ultrasound were analyzed and compared with muscle luminance histograms, and neither HP nor LP showed changes before and after pressure stimulation. CONCLUSION: There was no change in the B-mode ultrasound in both the HP and the LP, and the muscle stiffness decreased. The muscle temperature also increased, but when looking at the oxygen saturation level, only the HP showed a high value, indicating an increase in blood flow rate.

The impact of blood flow rate on dialysis dose and phosphate removal in hemodialysis patients.

The inadequacy of dialysis and hyperphosphatemia are both associated with morbidity and mortality in chronic hemodialysis (HD) patients. Blood flow rate (BFR) during HD is one of the important determinants of increasing dialysis dose. The aim of this study was to determine the effect of increasing BFR on dialysis dose and phosphate removal. Forty-four patients were included in a cross-sectional study. Each patient received six consecutive dialysis sessions as follows: three consecutive sessions with a BFR of 250 mL/min, followed by three others with BFR of 350 mL/min without changing the other dialysis parameters. Patients' body weight was recorded, and blood samples (serum urea and phosphate) were collected before and after each dialysis session. For assessing the efficacy of dialysis, urea reduction ratio (URR), Kt/VDiascan (Kt by Diascan and V by Watson), Kt/V Daugirdas (Daugirdas 2nd generation), equilibrated Kt/V, and phosphate reduction rate (PRR) were used. The increase of BFR by 100 mL/min resulted in a significant increase of URR, Kt/V Diascan, Kt/VDaugirdas, equilibrated Kt/V, and PRR: URR; 75.41 ± 5.60; 83.51 ± 6.12; P <0.001), (Kt/VDiascan; 1.28 ± 0.25; 1.55 ± 0.15; P <0.001), (Kt/VDaugirdas; 1.55 ± 0.26; 2.10 ± 0.61; P = 0.001), equilibrated Kt/V; 1.40 ± 0.19; 1.91 ± 0.52; P = 0.001), and (PRR; 50.32 ± 12.22; 63.66 ± 13.10; P = 0.010). Adequate dialysis, defined by single-pool Kt/V ≥1.4, was achieved using two different BFRs: 250 and 350 mL/min, respectively, in 73% and 100% of the cases. Increasing the BFR by 40% is effective in increasing dialysis dose and phosphate reduction rate during high-flux HD. The future prospective studies are needed to evaluate the impact of increasing BFR on phosphate removal using the total amount of phosphate removed, and also evaluate the cardiovascular outcome of phosphate reduction and dialysis improvement.

Assessment of hemodialysis efficacy in patients with end-stage renal failure in the erbil hemodialysis center

Background: Adequate and effective hemodialysis (HD) improves health-related quality of life and reduces morbidity and mortality in patients with end-stage renal disease (ESRD). The efficacy of dialysis procedure applied on patients diagnosed with ESRD was evaluated in the current investigation. Materials and Methods: In the present pre- and post-test cohort study, out of 375 patients, 120 patients (46 males and 74 females) on thrice-weekly chronic HD program were followed up over 6 months for evaluation of dialysis efficacy and possible outcomes. The efficacy of HD was measured through the Kt/V method and urea reduction ratio (URR). Results: The current study showed that the studied population (thrice-weekly HD patients) represents a minority of patients, i.e., 35.2% (132 of 375), and all other receiving insufficient HD treatment usually on twice weekly around 3 h for each session (64.8%). The study showed that the dialysis adequacy of the patients reached an adequate level by Kt/v and URR, 73.3% and 68.3%, respectively; the dialysis adequacy was increased with an increase in blood flow rate (P = 0.042), dialysis session time (P = 0.005), and dialysis sessions (P = 0.008). Patients with lower body mass index and without comorbidities were more likely to have adequate dialysis (P = 0.004 and P = 0.02, respectively). Conclusions: HD treatment is suboptimal in Erbil Dialysis Center. Intensive follow-up and application of corrective measures may improve dialysis efficacy. Energetic efforts are required to examine and correct the reasons behind the dialysis inadequacy.

Detection of microembolic signals in the common carotid artery using Doppler sonography in the porcine model of acute heart failure treated by veno-arterial extracorporeal membrane oxygenation.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a method used for the treatment most severe cases of decompensated heart failure. The purpose of this study was to evaluate the risk of the formation of microembolisms during VA-ECMO-based therapy. Heart failure was induced with simultaneous detection of microembolisms and the measurement of blood flow rate in the common carotid artery (CCA) without VA-ECMO (0 l/min) and at the VA-ECMO blood flow rate of 1, 2, 3 and 4 l/min. If embolisms for VA-ECMO 0 l/min and the individual regimes for VA-ECMO 1, 2, 3, 4 l/min are compared, a higher VA-ECMO flow rate is accompanied by a higher number of microembolisms. The final microembolism value at 16 min was for the VA-ECMO flow rate of 0 l/min 0.0 (0, 1), VA-ECMO l/min 7.5 (4, 19), VA-ECMO 2 l/min 12.5 (4, 26), VA-ECMO 3 l/min, 21.0 (18, 57) and VA-ECMO 4 l/min, 27.5 (21, 64). Such a comparison is statistically significant if VA-ECMO 0 vs. 4 l/min p<0.0001, 0 vs. 3 l/min p<0.01 and 1 vs. 4 l/min p<0.01 are compared. The results confirm that high VA-ECMO flow rates pose a risk with regards to the formation of a significantly higher number of microemboli in the blood circulation and that an increase in blood flow rates in the CCA corresponds to changes in the VA-ECMO flow rates.

Effect of first cannulation time and dialysis machine blood flows on survival of arteriovenous fistulas.

To study the effect of cannulation time on arteriovenous fistula (AVF) survival. Methods. Analysis of two prospective databases of access operations and dialysis sessions from 12 January 2002 through 4 January 2015 with follow-up until 4 January 2016. First cannulation time (FCT), defined from operation to first cannulation, was categorized as <2 weeks, 2-4 weeks, 4-8 weeks, 8-16 weeks and ≥16 weeks. Early cannulation was defined as FCT within 4 weeks. AVF survival was defined as the date until the AVF was abandoned. Maximum machine blood flow rate (BFR) for the first 29 dialysis sessions on AVF was analysed. Altogether, 1167 AVF with functional dialysis use were analysed: 667 (57%) radial cephalic AVF, 383 (33%) brachiocephalic AVF and 117 (10%) brachiobasilic AVF. The 631 (54%) AVF created in on-dialysis patients were analysed separately from 536 (46%) AVF created in pre-dialysis patients. AVF survival was similar between cannulation categories for both pre-dialysis patients (P = 0.19) and on-dialysis patients (P = 0.83). Early cannulation was associated with similar AVF survival in both pre-dialysis patients (P = 0.82) and on-dialysis patients (P = 0.17). Six consecutive successful cannulations from the start were associated with improved AVF survival (P = 0.0002). A below-median BFR at the start of dialysis was associated with better AVF survival (P < 0.0001). A below-median increase in BFR in the first 2 months was associated with worse AVF survival (P = 0.007). The type of AVF, diabetes, pre-dialysis state at operation and six successful cannulations from the start were independent predictors for AVF survival. FCT is not associated with AVF survival. Failures to achieve six successful cannulations from the start of dialysis and higher machine BFR in the first week of dialysis are associated with decreased AVF survival.

A novel mathematical model of protein-bound uremic toxin kinetics during hemodialysis

Protein-bound uremic toxins (PBUTs) are difficult to remove by conventional hemodialysis; a high degree of protein binding reduces the free fraction of toxins and decreases their diffusion across dialyzer membranes. Mechanistic understanding of PBUT kinetics can open new avenues to improve their dialytic removal. We developed a comprehensive model of PBUT kinetics that comprises: (1) a three-compartment patient model, (2) a dialyzer model. The model accounts for dynamic equilibrium between protein, toxin, and the protein-toxin complex. Calibrated and validated using clinical and experimental data from the literature, the model predicts key aspects of PBUT kinetics, including the free and bound concentration profiles for PBUTs and the effects of dialysate flow rate and dialyzer size on PBUT removal. Model simulations suggest that an increase in dialysate flow rate improves the reduction ratio (and removal) of strongly protein-bound toxins, namely, indoxyl sulfate and p-cresyl sulfate, while for weakly bound toxins, namely, indole-3-acetic acid and p-cresyl glucuronide, an increase in blood flow rate is advantageous. With improved dialyzer performance, removal of strongly bound PBUTs improves gradually, but marginally. The proposed model can be used for optimizing the dialysis regimen and for in silico testing of novel approaches to enhance removal of PBUTs.

Pereskia aculeata Miller leaves accelerate excisional wound healing in mice

Ethnopharmacological relevanceThe leaves of Pereskia aculeata Miller (Cactaceae), known as Barbados gooseberry, are used as emollients and to treat skin wounds and inflammatory process in Brazilian traditional medicine. Aim of the studyThis study investigated the topical wound healing activity of gels containing the methanol extract (ME) and hexane fraction (HF) of the leaves of this plant in a model of excisional wound healing in mice. Material and methodsMice were anesthetized and excisional skin wounds were performed using a circular metal punch of 5mm diameter. Next, the animals were treated with 30µL of topical gel formulations containing the gel base (vehicle), HF 5% or ME 5%. The treatments were applied immediately after the injury and every 48h during 14 days. To verify the wound closure kinetics, a digital caliper was used throughout this period. Laser Doppler perfusion image (LDPI) was applied to evaluate the blood flow rate at the injury site. Microscopic examination of the skin tissues was performed by histopathological analysis with hematoxylin and eosin and Gomori trichrome staining. Picrosirius-red staining was also used for morphometric analysis for collagen quantification. ResultsBoth HF and ME markedly accelerated the closeness of the skin wounds; however the HF activity was more evident, as this fraction induced the increase of blood flow rate and collagen deposition when statistically compared to the vehicle. The mice skin treated with HF and ME also showed less fibroplasia, blood vessels and inflammatory cells on the last day of experiment, which indicated a more advanced wound healing process. ConclusionsAs the wound healing process was considerably accelerated, especially by HF gel formulation, the results of this study not only contributed to better understand the ethnopharmacological application of P. acuelata leaves, but also encouraged further investigations on how to explore the potential uses of this plant in skin therapies.

Computational particle–haemodynamics analysis of liver radioembolization pretreatment as an actual treatment surrogate

Liver radioembolization (RE) is a treatment option for patients with unresectable and chemorefractory primary and metastatic liver tumours. RE consists of intra-arterially administering via catheter radioactive microspheres that locally attack the tumours, sparing healthy tissue. Prior to RE, the standard practice is to conduct a treatment-mimicking pretreatment assessment via the infusion of 99m Tc-labelled macroaggregated albumin microparticles. The usefulness of this pretreatment has been debated in the literature, and thus, the aim of the present study is to shed light on this issue by numerically simulating the liver RE pretreatment and actual treatment particle-haemodynamics in a patient-specific hepatic artery under two different literature-based cancer scenarios and two different placements of a realistic end-hole microcatheter in the proper hepatic artery. The parameters that are analysed are the following: microagent quantity and size (accounting for RE pretreatment and treatment), catheter-tip position (near the proper hepatic artery bifurcation and away from it), and cancer burden (10% and 30% liver involvement). The conclusion that can be reached from the simulations is that when it comes to mimicking RE in terms of delivering particles to tumour-bearing segments, the catheter-tip position is much more important (because of the importance of local haemodynamic pattern alteration) than the infused microagents (i.e. quantity and size). Cancer burden is another important feature because the increase in blood flow rate to tumour-bearing segments increases the power to drag particles. These numerical simulation-based conclusions are in agreement with clinically observed events reported in the literature. Copyright © 2016 John Wiley & Sons, Ltd.

Ectotherms’ cardiovascular upgrade for endothermic lifestyle

Keeping warm has its advantages. Endotherms, which maintain a constant raised body temperature, keep going no matter how chilly their surroundings. Meanwhile, ectotherms are at the behest of the environment: many have to sit tight until they have absorbed enough warmth to function. But which physiological systems did our ectothermic ancestors have to upgrade for us to benefit from internal central heating? Stanley Hillman from Portland State University, USA, and Michael Hedrick from California State University East Bay, USA, explain that there are two competing theories: that ectotherms increased the number of mitochondria in muscle and modified the energy-producing organelles to upgrade to an endothermic lifestyle; or, our ancestors expanded the cardiovascular system to supply the additional oxygen required to fuel our costly, high-temperature way of life. With evidence stacking up on both sides, Hillman and Hedrick decided to review the differences between the cardiovascular systems of ectotherms and endotherms to find out whether expanding the cardiovascular system allowed endotherms to turn up the thermostat.First, the duo scoured the literature for cardiovascular measurements from a wide range of exercising animals – from ectothermic fish and amphibians to endothermic birds and mammals – to put their theory to the test. But there was one glaring omission: ‘a gap existed in the data for reptiles for [cardiac] flow and pressure during exercise’, they say, before accepting – after contacting many colleagues – that the measurements have yet to be made. However, despite the setback, they interrogated the data to identify differences between the cardiovascular systems of exercising ectotherms and endotherms to find out just how hard the animals’ hearts can work.Calculating the vascular conductance, cardiac power and work done per heart beat (stroke work), Hillman and Hedrick found that endotherms’ hearts pumped blood at a higher pressure (17.1 kPa vs 3.3 kPa for the ectotherms) and at a higher heart rate (∼5 beats s–1 compared with the ectotherms’ ∼1 beat s–1), allowing the exercising endotherms to produce higher exercise cardiac power. And when they compared the relative size of the endotherms’ and ectotherms’ hearts, they found that the endotherms’ larger hearts enabled them to increase their blood pressure. They say, ‘A major difference between ectotherms and endotherms is the large increase in blood flow rates’, which is largely due to their higher heart rates and allows endotherms to increase the oxygen supply to the power-hungry muscles that keep them warm. However, the duo also found every mW of cardiac power supports a remarkable 158 mW of aerobic power output (which is only 0.6% of the exercise aerobic energy expense) regardless of the animal's lifestyle, showing that the cost of circulation is low for endo- and ectotherms alike.Focusing on the cardiac changes that were essential for ectotherms to warm up, Hillman and Hedrick explain that our ancestors had to remove the cardiac shunts – which allow amphibians and reptiles to mix oxygenated and deoxygenated blood – to increase oxygen transport. They also had to increase their heart rates by developing the sarcoplasmic reticulum – which controls the calcium levels in muscle that regulate muscle contraction – to increase the heart rate. And finally, endotherms had to increase their cardiac muscle mass relative to the body mass of similarly sized ectotherms to produce the higher blood flow rates that are essential for a metabolically demanding endothermic lifestyle.The duo says, ‘These results suggest that a key step in the support of endothermy was the greatly enhanced ability of the cardiovascular system to deliver oxygen which accounted for the approximately ten-fold increase in aerobic scope between endotherms and ectotherms’.

Role of local hemodynamic abnormalities at pathologic tortuosity of the carotid arteries in development of vascular cerebral insufficiency

Turbulence in blood flow in patients with pathological tortuosity of the internal carotid artery at a rate in excess of 1 m/s (Re &gt; 1140), the occurrence of wall surface vortices and increase of blood flow rate by reducing the hydraulic diameter of the arteries result in the increased hemodynamic resistance of the vasculature and the brain hypoperfusion. Variety of forms and the complexity of the geometric configuration of arteries in their pathological tortuosity require an individual approach in determining the indications for surgical treatment and the choice of method of operation. The paper describes the objective biomechanical criteria based on instrumental clinical studies of hemodynamic disturbances and determining the pressure gradient in the areas of changing the geometry of blood vessels. The integrated use of anatomic and hemodynamic parameters allows us to estimate the energy losses and pressure gradients in pathological tortuosity of the internal carotid arteries in any geometric configuration. The extension of the proximal portion of the artery with respect to the pathological curvature was found which caused by the fact that the diameter of the mouth of the carotid artery with unilateral pathological tortuosity exceeds diameter of the mouth on the contralateral side. It was showed the occurrence of parietal swirl flow corresponds to a rate of 1.2 m/s and the total turbulence – at a speed of 1.4 m/s in the arteries with diameter of 4 mm. Flow rate at which a swirl flow is 0.8 m/s and a turbulent blood flow is recorded at a rate of 1 m/s by increasing the diameter of the carotid artery to 6 mm.

Nitric oxide-mediated vasodilation increases blood flow during the early stages of stress fracture healing

Despite the strong connection between angiogenesis and osteogenesis in skeletal repair conditions such as fracture and distraction osteogenesis, little is known about the vascular requirements for bone formation after repetitive mechanical loading. Here, established protocols of damaging (stress fracture) and nondamaging (physiological) forelimb loading in the adult rat were used to stimulate either woven or lamellar bone formation, respectively. Positron emission tomography was used to evaluate blood flow and fluoride kinetics at the site of bone formation. In the group that received damaging mechanical loading leading to woven bone formation (WBF), (15)O water (blood) flow rate was significantly increased on day 0 and remained elevated 14 days after loading, whereas (18)F fluoride uptake peaked 7 days after loading. In the group that received nondamaging mechanical loading leading to lamellar bone formation (LBF), (15)O water and (18)F fluoride flow rates in loaded limbs were not significantly different from nonloaded limbs at any time point. The early increase in blood flow rate after WBF loading was associated with local vasodilation. In addition, Nos2 expression in mast cells was increased in WBF-, but not LBF-, loaded limbs. The nitric oxide (NO) synthase inhibitor N(ω)-nitro-l-arginine methyl ester was used to suppress NO generation, resulting in significant decreases in early blood flow rate and bone formation after WBF loading. These results demonstrate that NO-mediated vasodilation is a key feature of the normal response to stress fracture and precedes woven bone formation. Therefore, patients with impaired vascular function may heal stress fractures more slowly than expected.