Hemodynamic Changes Research Articles

Effect of esketamine on the ED50 of propofol for successful insertion of ureteroscope in elderly male patients: a randomized controlled trial

BackgroundPropofol is effective and used as a kind of routine anesthetics in procedure sedative anesthesia (PSA) for ureteroscopy. However, respiratory depression and unconscious physical activity always occur during propofol-based PSA, especially in elderly patients. Esketamine has sedative and analgesic effects but without risk of cardiorespiratory depression. The purpose of this study is to investigate whether esketamine can reduce the propofol median effective dose (ED50) for successful ureteroscope insertion in elderly male patients.Materials and methods49 elderly male patients undergoing elective rigid ureteroscopy were randomly divided into two groups: SK Group (0.25 mg/kg esketamine+propofol) and SF Group (0.1 µg/kg sufentanil+propofol). Patients in both two groups received propofol with initial bolus dose of 1.5 mg/kg after sufentanil or esketamine was administered intravenously. The effective dose of propofol was assessed by a modified Dixon’s up-and-down method and then was adjusted with 0.1 mg/kg according to the previous patient response. Patients’ response to ureteroscope insertion was classified as “movement” or “no movement”. The primary outcome was the ED50 of propofol for successful ureteroscope insertion with esketamine or sufentanil. The secondary outcomes were the induction time, adverse events such as hemodynamic changes, hypoxemia and body movement were also measured.Result49 patients were enrolled and completed this study. The ED50 of propofol for successful ureteroscope insertion in SK Group was 1.356 ± 0.11 mg/kg, which was decreased compared with that in SF Group, 1.442 ± 0.08 mg/kg (P = 0.003). The induction time in SK Group was significantly shorter than in SF Group (P = 0.001). In SK Group, more stable hemodynamic variables were observed than in SF Group. The incidence of AEs between the two groups was not significantly different.ConclusionThe ED50 of propofol with esketamine administration for ureteroscope insertion in elderly male patients is 1.356 ± 0.11 mg/kg, significantly decreased in comparsion with sufentanil.Trial registrationChinese Clinical Trial Registry, No: ChiCTR2300077170. Registered on 1 November 2023. Prospective registration. http://www.chictr.org.cn.

Physiological mechanisms behind respiratory variations in right atrial pressure in pulmonary hypertension

Impaired respiratory variation of right atrial pressure (RAP) in severe pulmonary hypertension (PH) suggests difficulty tolerating increased preload during inspiration. Our study explores whether this impairment links to specific factors: right ventricular (RV) diastolic function, elevated RV afterload, systolic RV function, or RV-pulmonary arterial (PA) coupling. We retrospectively evaluated respiratory RAP variation in all participants enrolled in the EXERTION study. Impaired respiratory variation was defined as end-expiratory RAP − end-inspiratory RAP ≤ 2 mm Hg. RV function and afterload were evaluated using conductance catheterization. Impaired diastolic RV function was defined as end-diastolic elastance (Eed) ≥ median (0.19 mm Hg/mL). Seventy-five patients were included; PH was diagnosed in 57 patients and invasively excluded in 18 patients. Of the 75 patients, 31 (41%) had impaired RAP variation, which was linked with impaired RV systolic function and RV-PA coupling and increased tricuspid regurgitation and Eed as compared to patients with preserved RAP variation. In backward regression, RAP variation associated only with Eed. RAP variation but not simple RAP identified impaired diastolic RV function (area under the receiver operating characteristic curve [95% confidence interval]: 0.712 [0.592, 0.832] and 0.496 [0.358, 0.634], respectively). During exercise, patients with impaired RAP variation experienced greater RV dilatation and reduced diastolic reserve and cardiac output/index compared with patients with preserved RAP variation. Preserved RAP variation was associated with a better prognosis than impaired RAP variation based on the 2022 European Society of Cardiology/European Respiratory Society risk score (chi-square P = 0.025) and survival free from clinical worsening (91% vs 71% at 1 year and 79% vs 50% at 2 years [log-rank P = 0.020]; hazard ratio: 0.397 [95% confidence interval: 0.178, 0.884]). Subgroup analyses in patients with group 1 and group 4 PH demonstrated consistent findings with those observed in the overall study cohort. Respiratory RAP variations reflect RV diastolic function, are independent of RV-PA coupling or tricuspid regurgitation, are associated with exercise-induced haemodynamic changes, and are prognostic in PH.Trial registration. NCT04663217.

Comparison of Hemodynamic Response to Endotracheal Intubation with Nebulized Lignocaine and Dexmedetomidine: a Prospective Randomized Controlled Trial

Background: Though different studies have compared intravenous (IV) lignocaine with dexmedetomidine for blunting laryngoscopic and intubation response, there is hardly any study comparing nebulized Lignocaine and dexmedetomidine for the same. This study compared the effectiveness of nebulized dexmedetomidine and Lignocaine for blunting hemodynamic response to laryngoscopy and intubation. Methods: This prospective randomized double-blinded study among 60 patients was divided into two equal groups of 30 (groups D and L). Group D patients were nebulized with 1 µg/kg of dexmedetomidine diluted in 0.9% saline to a total volume of 4 ml, and Group L patients were nebulized with 4ml of 4% Lignocaine hydrochloride in the preoperative room over 5 min. After induction of general anesthesia, laryngoscopy and intubation were performed, and hemodynamic changes were recorded for statistical analysis. A two-sample t-test was applied to compare means in two groups with a confidence interval of 95%. Result The Dexmedetomidine group demonstrated a significant difference, with lower values of mean heart, systolic, diastolic, and mean arterial pressure rate immediately before laryngoscopy till 10 minutes postintubation (recorded at 2 mins intervals till 10mins) compared to the lignocaine group. The p-values for all the parameters were < 0.001, underlining the robustness of our findings. Conclusion: Nebulised Dexmedetomidine before laryngoscopy is not just an alternative technique, but a superior one for blunting the hemodynamic response to laryngoscopy and endotracheal intubation. It outperforms Nebulised Lignocaine without significant adverse effects, such as postoperative sore throat and sedation, making a compelling case for its adoption in clinical practice.

Revascularisation patterns and characteristics after erythropoietin pretreatment and multiple burr holes in patients who had acute stroke with perfusion impairment

BackgroundTransdural collaterals, originating mainly from the extracalvarial superficial temporal artery and intracalvarial middle meningeal artery via the external carotid artery (ECA), have been observed after revascularisation surgery. However, the origin...

Parkinson's disease patients show delayed hemodynamic changes in primary motor cortex in fine motor tasks and decreased resting-state interhemispheric functional connectivity: a functional near-infrared spectroscopy study.

People with Parkinson's disease (PD) experience changes in fine motor skills, which is viewed as one of the hallmark signs of this disease. Due to its non-invasive nature and portability, functional near-infrared spectroscopy (fNIRS) is a promising tool for assessing changes related to fine motor skills. We aim to compare activation patterns in the primary motor cortex using fNIRS, comparing volunteers with PD and sex- and age-matched control participants during a fine motor task and walking. Moreover, inter and intrahemispheric functional connectivity (FC) was investigated during the resting state. We used fNIRS to measure the hemodynamic changes in the primary motor cortex elicited by a finger-tapping task in 20 PD patients and 20 controls matched for age, sex, education, and body mass index. In addition, a two-minute walking task was carried out. Resting-state FC was also assessed. Patients with PD showed delayed hypoactivation in the motor cortex during the fine motor task with the dominant hand and delayed hyperactivation with the non-dominant hand. The findings also revealed significant correlations among various measures of hemodynamic activity in the motor cortex using fNIRS and different cognitive and clinical variables. There were no significant differences between patients with PD and controls during the walking task. However, there were significant differences in interhemispheric connectivity between PD patients and control participants, with a statistically significant decrease in PD patients compared with control participants. Decreased interhemispheric FC and delayed activity in the primary motor cortex elicited by a fine motor task may one day serve as one of the many potential neuroimaging biomarkers for diagnosing PD.

Pneumonectomy combined with SU5416 or monocrotaline pyrrole does not cause severe pulmonary hypertension in mice.

In the field of pulmonary hypertension (PH), a well-established protocol to induce severe angioproliferation in rats (SuHx) involves combining the VEGF-R inhibitor Sugen 5416 (SU5416) with three weeks of hypoxia (Hx). Additionally, injecting monocrotaline (MCT) into rats can induce inflammation and shear stress in the pulmonary vasculature, leading to neointima-like remodeling. However, the SuHx protocol in mice is still controversial, with some studies suggesting it yields higher and reversible PH than Hx alone, possibly due to species-dependent hypoxic responses. To establish an alternative rodent model of PH, we hypothesized mice would be more sensitive to hemodynamic changes secondary to shear stress compared to Hx. We attempted to induce severe and irreversible PH in mice by combining SU5416 or monocrotaline pyrrole (MCTP) injection with pneumonectomy (PNx). However, our experiments showed SU5416 administered to mice at various time points after PNx did not result in severe PH. Similarly, mice injected with MCTP after PNx (MPNx) showed no difference in right ventricular systolic pressure or exacerbated pulmonary vascular remodeling compared to PNx alone. These findings collectively demonstrate that C57/B6 mice do not develop severe and persistent PH when PNx is combined with either SU5416 or MCTP.

Echocardiographic assessment of cardiovascular physiology of preterm miniature piglets supported with a pumped artificial placenta system.

We evaluated fetal cardiovascular physiology and mode of cardiac failure in premature miniature piglets on a pumped artificial placenta (AP) circuit. Fetal pigs were cannulated via the umbilical vessels and transitioned to an AP circuit composed of a centrifugal pump and neonatal oxygenator and maintained in a fluid-filled biobag. Echocardiographic studies were conducted to measure ventricular function, umbilical blood flow, and fluid status. In utero scans were used as control data. AP fetuses (n=13; 102±4d gestational age [term 115d]; 616±139g [g]; survival 46.4±46.8h) were tachycardic and hypertensive with initially supraphysiologic circuit flows. Increased myocardial wall thickness was observed. Signs of fetal hydrops were present in all piglets. Global longitudinal strain (GLS) measurements increased in the left ventricle (LV) after transition to the circuit. Right ventricle (RV) and LV strain rate decreased early during AP support compared with in utero measurements but recovered toward the end of the experiment. Fetuses supported for >24h had similar RV GLS to in utero controls and significantly higher GLS compared to piglets surviving only up to 24h. Fetuses on a pump-supported AP circuit experienced an increase in afterload, and redistribution of blood flow between the AP and systemic circulations, associated with elevated end-diastolic filling pressures. This resulted in heart failure and hydrops. These preterm fetuses were unable to tolerate the hemodynamic changes associated with connection to the current AP circuit. To better mimic the physiology of the native placenta and preserve normal fetal cardiovascular physiology, further optimization of the circuit will be required.

Interaction of Angiotensin-(1−7) with kinins in the kidney circulation: Role of B1 receptors

Changes in renal hemodynamics impact renal function during physiological and pathological conditions. In this context, renal vascular resistance (RVR) is regulated by components of the Renin-Angiotensin System (RAS) and the Kallikrein-Kinin System (KKS). However, the interaction between these vasoactive peptides on RVR is still poorly understood. Here, we studied the crosstalk between angiotensin-(1−7) and kinins on RVR. The right kidneys of Wistar rats were isolated and perfused in a closed-circuit system. The perfusion pressure and renal perfusate flow were continuously monitored. Ang-(1−7) (1.0–25.0 nM) caused a sustained, dose-dependent reduction of relative RVR (rRVR). This phenomenon was sensitive to 10 nM A-779, a specific Mas receptor (MasR) antagonist. Bradykinin (BK) promoted a sustained and transient reduction in rRVR at 1.25 nM and 125 nM, respectively. The transient effect was abolished by 4 μM des-Arg9-Leu8-bradykinin (DALBK), a specific kinin B1 receptor (B1R) antagonist. Accordingly, des-Arg9-bradykinin (DABK) 1 μM (a B1R agonist) increased rRVR. Interestingly, pre-perfusion of Ang-(1−7) changed the sustained reduction of rRVR triggered by 1.25 nM BK into a transient effect. On the other hand, pre-perfusion of Ang-(1−7) primed and potentiated the DABK response, this mechanism being sensitive to A-779 and DALBK. Binding studies performed with CHO cells stably transfected with MasR, B1R, and kinin B2 receptor (B2R) showed no direct interaction between Ang-(1−7) with B1R or B2R. In conclusion, our findings suggest that Ang-(1−7) differentially modulates kinin's effect on RVR in isolated rat kidneys. These results help to expand the current knowledge regarding the crosstalk between the RAS and KKS complex network in RVR.

Prenatal diagnosis and perinatal clinical course of isolated left-sided innominate artery.

Isolated left-sided innominate artery, a rare congenital anomaly in which the left-sided innominate artery arises from the main pulmonary trunk, is usually diagnosed incidentally in children and adults. Limited reports exist on its prenatal diagnosis, with none comprehensively describing the associated perinatal haemodynamic changes. We report a case of prenatally diagnosed isolated left-sided innominate artery, describing the postnatal clinical course.

Radiomics features of the cardiac blood pool to indicate hemodynamic changes in pulmonary hypertension (PH) due to heart failure with preserved ejection fraction (PH-HFpEF).

To test the hypothesis that cine MRI-derived radiomics features of the cardiac blood pool can represent hemodynamic characteristics of pulmonary hypertension-heart failure with preserved ejection fraction (PH-HFpEF). Nineteen PH-HFpEF patients (9 male, 57.8 ± 14.7 years) and 19 healthy controls (13 male, 50.3 ± 13.6 years) were enrolled. All participants underwent a cardiac MRI scan. One hundred and seven radiomics features (7 classes) of the blood pool in the left and right ventricles/atrium (LV/RV/LA/RA) were extracted from 4-chamber cine (2D images) at the stages of systole, rapid filling, diastasis, and atrial contraction within a cardiac cycle. For PH-HFpEF patients, features acquired from LV/LA were related to the pulmonary capillary wedge pressure (PCWP); features acquired from RV/RA were related to the mean pulmonary artery pressure (mPAP) using the Pearson correlation coefficient (r). Logistic regression, receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to test the capability of radiomics features in discriminating 2 subject groups. Features acquired from different chambers at various periods present diverse properties in representing hemodynamic indices of PH-HFpEF. Multiple radiomics features blood pool were significantly related to PCWP and/or mPAP (r: 0.4-0.679, p < 0.05). In addition, multiple features of blood pools acquired at various time points within a cardiac cycle can efficiently discriminate PH-HFpEF from controls (individual AUC: 0.7-0.864). Cine MRI-derived radiomics features of the cardiac blood pool have the potential to characterize hemodynamic abnormalities in the context of PH-HFpEF.

Invasive Hemodynamic Changes Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to lower incident heart failure (HF) and HF hospitalizations, but the mechanisms of benefit in relation to invasive hemodynamics remain unclear. Using PRISMA guidelines, we systematically reviewed multiple online databases for randomized trials evaluating the effect of SGLT2i on invasive hemodynamics. Rest and peak exercise invasive hemodynamics were measured via right heart catheterization pre- and postintervention. Random effects model meta-analysis at a 95% confidence interval was done using RevMan 5.0. A total of 3 studies with a total of 145 patients were included in the meta-analysis. SGLT2i was significantly associated with a reduction in pulmonary capillary wedge pressure at rest and peak exercise. Similarly, SGLT2i reduced mean pulmonary artery pressure at rest and peak exercise, respectively; however, this was not statistically significant. This hypothesis-generating study offers mechanistic insights into the central hemodynamic effects of SGLT2i underpinning the HF benefits of SGLT2i.

Hemodynamic changes in the prone position according to fluid loading after anaesthesia induction in patients undergoing lumbar spine surgery: a randomized, assessor-blind, prospective study

Introduction A change from the supine to prone position causes hemodynamic alterations. We aimed to evaluate the effect of fluid preloading in the supine position, the subsequent hemodynamic changes in the prone position and postoperative outcomes. Patients and methods This prospective, assessor-blind, randomized controlled trial was conducted between March and June 2023. Adults scheduled for elective orthopaedic lumbar surgery under general anaesthesia were enrolled. In total, 80 participants were randomly assigned to fluid maintenance (M) or loading (L) groups. Both groups were administered intravenous fluid at a rate of 2 ml/kg/h until surgical incision; Group L was loaded with an additional 5 ml/kg intravenous fluid for 10 min after anaesthesia induction. The primary outcome was incidence of hypotension before surgical incision. Secondary outcomes included differences in the mean blood pressure (mBP), heart rate, pleth variability index (PVi), stroke volume variation (SVV), pulse pressure variation (PPV), stroke volume index and cardiac index before surgical incision between the two groups. Additionally, postoperative complications until postoperative day 2 and postoperative hospital length of stay were investigated. Results Hypotension was prevalent in Group M before surgical incision and could be predicted by a baseline PVi >16. The mBP was significantly higher in Group L immediately after fluid loading. The PVi, SVV and PPV were lower in Group L after fluid loading, with continued differences at 2–3 time points for SVV and PPV. Other outcomes did not differ between the two groups. Conclusion Fluid loading after inducing general anaesthesia could reduce the occurrence of hypotension until surgical incision in patients scheduled for surgery in the prone position. Additionally, hypotension could be predicted in patients with a baseline PVi >16. Therefore, intravenous fluid loading is strongly recommended in patients with high baseline PVi to prevent hypotension after anaesthesia induction and in the prone position. Trial number KCT0008294 (date of registration: 16 March 2023)

Acute hemodynamic effects of the Marshall-Plan ablation on left and right atrial pressure: does 'respecting atrial physiology' prevent stiff left atria? A retrospective single- center analysis

Abstract Introduction Stiff left atrium (STILA)-syndrome is a relevant concern after extensive ablation in the left atrium (LA) e.g. in persistent atrial fibrillation (AF). STILA often causes disabling heart failure symptoms worse than the initial arrhythmia symptoms. Therefore preventing adverse ablation-induced hemodynamic effects is of utmost concern. Methods This single-center study retrospectively analyzed data from 89 consecutive patients who underwent biatrial ablation for AF following the Marshall-Plan between February 2022 and November 2023. The procedures included ablation of the CTI and PVI where necessary followed by ablation of a LA roof line and ablation of the lateral mitral isthmus after previously performed ethanol ablation of the vein of Marshall. This lesion set is considered to maintain physiological activation of the LA. This study evaluates acute hemodynamic changes following the Marshall-Plan. Invasive hemodynamic measurements of mean left and right atrial pressure, as well as A- and V-waves were performed in all patients before and after the ablation. We assessed the acute changes of atrial hemodynamics in these procedures. Continuous data are given as mean ± standard deviation, categorical data are expressed as number and percentages. Differences between groups were determined by Student’s t-test, chisquare-test, and Fisher’s exact test using SPSS software. A p-value of &amp;lt;0.05 was deemed significant. Results The patients' mean age was 70.1 ± 7.5 years and 39.0% were female. Mean BMI was 28.9 ± 5.2 kg/m². Procedures were performed under general anesthesia (with a PEEP of 5.5cmH2O (2-10 cmH2O)) and took 181 minutes on average. Left atrial mean pressure averaged at 15.7mmHg before the procedure. The overall average change of left atrial mean pressure was +1,8mmHg. The average change in left atrial A- and V-Wave amounted to -1.9mmHg and -0.9mmHg respectively. The pre-procedural average right atrial mean pressure was 12.1mmHg. Right atrial mean pressure inclined by +1.6mmHg. The average change in right atrial A- and V-Wave was +0.6mmHg and +1.1mmHg respectively. The i.v. administered volume averaged 1900 ± 285ml. 3.3% of patients showed an increase of mean LA-pressure &amp;gt;9mmHg. Those patients tended to be older (74.3years), were all male (100%) and had a higher BMI (31.5 kg/m²) as well as higher amount of i.v. administered volume (2333ml) and a longer procedure (213min). Discussion Complex and extensive biatrial ablation following the Marshall-Plan does not lead to acute significant increases in left or right atrial pressures. The administered i.v. volume might explain the slight increases observed. In our observation, the rate of significant increases in LA-pressure is low. This suggests that disrupting the (left) atrial activation pattern might play a role in the development of diastolic dysfunction and thereby STILA-syndrome. Respecting atrial physiology may be beneficial for preventing adverse hemodyamic changes after ablation.

Acute haemodynamic changes during left atrial appendage closure

Abstract Purpose Left atrial appendage closure (LAAC) presents an alternative treatment for stroke prevention in atrial fibrillation (AF) in patients with contraindication for long-term anticoagulation. However, even in patients in AF, left atrial appendage plays an important role in reservoir function of left atrium. The purpose of this study was to assess acute hemodynamic effects during LAAC. Methods Consecutive patients indicated for LAAC from January 2022 to October 2023 were enrolled. The invasive hemodynamic measurements were done at the beginning of the procedure after transseptal puncture, and at the end from the procedure after device deployment. Following parameters were measured: systolic, and diastolic blood pressure, and pressure in left atrium (LA), all measurements were done at rest and after 3 minute isometric exercise (handgrip). Results Thirty-two patients were included (age 76,2+7,1 yrs, 22 (69%) males, 23 (72%) permanent AF, left ventricular ejection fraction 52+11,8%). No patients experienced moderate/severe mitral insufficiency, the saline intake during procedure was 738 ml. Isometric exercise significantly increased the LA pressure: the LA pressures (rest/exercise) were 13.7+6.7 mmHg/16.7+8.8 mmHg (p=0.003) at the beginning of the procedure, and 17.0+7.3mmHg/20.0+7.3 mmHg (p=0.005) after device deployment. The LA pressure obtained after device deployment (both rest/exercise) were significantly higher compared to values obtained at the beginning of the procedure. (p=0.003). Conclusions LAAC is associated acute increase of both rest and exercise LA pressure. Whether its acute negative effect remains over time needs further investigation.

#1819 Cardio-fistular recirculation in patients with chronic heart failure and preserved ejection fraction

Abstract Background and Aims Cardio-fistular recirculation (CFR)—ratio of cardiac output (CO) to AVF volume blood flow (Qa)—is a well-known risk factor for death and cardiovascular adverse events. Currently, there are no clear limits for this index that definitely indicate AVF cardiotoxicity. In most cases, an interval score of &amp;lt;20%, 20-30%, or &amp;gt;30% is used to denote low, medium, and high risk, respectively. Typically, the assessment is performed on the interdialysiс day. HD sessions can cause significant hemodynamic changes, which may be important for patients with chronic heart failure (CFH) and preserved ejection fraction (EF), in whom the risk may be underestimated. The aim of this prospective cohort study is to evaluate changes in heart structure and CFR in patients with СFH and preserved EF before and after an HD session. Method The study included 20 stable adult HD patients who met the inclusion criteria: CHF with preserved EF (50%), NYHA I-II, Qa ≥1 l/min, CFR &amp;lt; 30%, interdialysiс weight gain &amp;lt; 5%, eKt/V &amp;gt; 1.2. Non-inclusion criteria: arrhythmias (except grade I AV block), NYHA III-IV, valvular disease (except mitral regurgitation I-II), intradialytic hypo/hypertension. All patients underwent transthoracic ECHO-CG with tissue Doppler on the third day after the last HD session (Monday/Tuesday), one hour before and 2 hours after the HD session. In addition, we measured AVF volume blood flow—brachial artery Qa. Results Patient Descriptive Statistics: M/F 8/12, mean age 52.2 (SD 11.2, range 41-67) years, HD vintage 49 (11.1, 33-72) months, BMI 28.2 (3.8, 22.9-36.0) kg/m2, interdialysiс weight gain 3.2 (0.8, 1.9-4.7) kg, relative interdialysiс weight gain 4.1% (0.8, 2.9-4.9). A significant trend in ECHO-CG parameters was observed, indicating a decrease in cardiac preload (Table 1). Although there were no significant changes in EF, a pronounced decrease in CO was noted with a relatively stable Qa value. As a result, 5 out of 20 patients had a CFR value of more than 30% after HD, which assigned them to a high-risk group. As shown in Fig. 1, even patients with pre-HD CFR values less than 25% were classified as high-risk. Patients were intentionally examined after a long interdialysiс interval because this HD session is associated with the greatest hemodynamic changes. Some publications suggest that the risk of death after long interdialysic interval is significantly higher than that after short interval. Increase in CFR after HD probably has a synergistic deleterious effect with other risk factors. The severity of this influence is determined by both the maximum achieved CFR values and the rate of CO recovery. Conclusion Some patients have a significant increase in CFR after HD. However, the prognostic value of this phenomenon remains unclear. In patients with significant CHF symptoms and normal or subnormal CFR on an interdialytic day, it is recommended to perform a post-HD examination. This can serve as a “stress test” to reveal any latent hemodynamic disadvantage caused by the AVF cardiotoxic effect.

Symposium review: high altitude travel with pulmonary vascular disease.

Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension are the main precapillary forms of pulmonary hypertension (PH) summarized as pulmonary vascular diseases (PVD). PVDs are characterized by exertional dyspnoea and oxygen desaturation, and reduced quality of life and survival. Medical therapies improve life expectancy and physical performance of PVD patients, of whom many wish to participate in professional work and recreational activities including traveling to high altitude. The exposure to the hypobaric hypoxic environment of mountain regions incurs the risk of high altitude adverse events (AEHA) due to severe hypoxaemia exacerbating symptoms and further increase in pulmonary artery pressure, which may lead to right heart decompensation. Recent prospective and randomized trials show that altitude-induced hypoxaemia, pulmonary haemodynamic changes and impairment of exercise performance in PVD patients are in the range found in healthy people. The vast majority of optimally treated stable PVD patients who do not require long-term oxygen therapy at low altitude can tolerate short-term exposure to moderate altitudes up to 2500m. PVD patients that reveal persistent severe resting hypoxaemia ( <80% for >30min) at 2500m respond well to supplemental oxygen therapy. Although there are no accurate predictors for AEHA, PVD patients with unfavourable risk profiles at low altitude, such as higher WHO functional class, lower exercise capacity with more pronounced exercise-induced desaturation and more severely impaired haemodynamics, are at increased risk of AEHA. Therefore, doctors with experience in PVD and high-altitude medicine should counsel PVD patients before any high-altitude sojourn. This review aims to summarize recent literature and clinical recommendations about PVD patients travelling to high altitude.

#930 Elevated glucose in kidney organoids induces epithelial detachment driven by proinflammatory cytokines

Abstract Background and Aims Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease affecting 40% of diabetics. The pathogenesis of DKD is linked with inflammation, altered metabolism, and hemodynamic change but the relationship between these factors is not well understood. Proteinuria and albuminuria are common features, suggesting that impairments in the renal glomerular filtration barrier may be among the primary disease initiators. Limited DKD models are available, which has hampered our disease understanding and the ability to develop new therapies. Therefore, creating an in-vitro model that harbors multiple renal cell types organized in their natural complex arrangement becomes an attractive option to fill in this gap. Here, we conducted a systematic investigation of the effects of high glucose on kidney organoids, with the goal of understanding whether these cultures can reflect specific features relevant to DKD. Method To evaluate the effect of high glucose, kidney organoids were differentiated until maturation (day 21) in standard glucose and then switched for six days to concentrations of 5.5, 11, 33 and 100 mM. Then, to test the effect of proinflammatory cytokines on the injury phenotypes we switched organoids, at day 21, in control glucose condition (11 mM) ± TNFα or high glucose (33 mM) ± inhibitors (TNFα). Morphology was analysed via immunostaining, LDH and live/dead assay were used for toxicity, qPCR and western blotting to investigate differences in gene and protein expression, and mannose was used as an osmotic control. scRNA-seq of organoid in 11 vs 33 mM was conducted to gain insight into the molecular mechanism(s) contributing to the high glucose. Results Organoids remain well preserved in glucose up to 11 mM whereas organoids cultured in 33 and 100 mM showed a ∼30% reduction in overall organoid number between days 3 and 6. Moreover, in high glucose (33 and 100 mM), we observed an increase in the number of small, single PODXL+ cells surrounding the main organoid body, suggesting detachment from the podocyte clusters that normally form in organoids (Fig. A). To quantify it, we divided the total PODXL+ area into two sub-regions, classified as intact area and detached area, and calculated their ratio (Fig. B). Results indicated a 2-fold reduction of the intact vs detached area between 11 and 33 mM (p = 0.0011), suggesting that organoids undergo a spreading process under the influence of high glucose (Fig. C). Comparison of equimolar glucose vs mannose, live/dead and LDH assays identify a non-osmotic and non-apoptotic cause of the injury. ScRNA-seq analysis identified TNF-α as an upregulated pathway, which was confirmed with qPCR (p = 0.0131). Comparison of organoids at 11mM ± TNFα indicated that TNFα addition sensitizes podocytes to detachment at lower glucose levels, specifically, we identified a 4-fold reduction of the PODXL+ intact vs detached area at 11 mM ± TNFα (p &amp;lt; 0.0001), Fig. D. To further validate these findings and investigate possible therapeutic strategies, organoids were cultured with 33 mM glucose with TNF-α inhibitor and we identified a protective effect of the inhibitor which prevented the podocyte spreading phenotype at 33 mM glucose (Fig. E). Conclusion Our experiments identify an injury phenotype under high glucose concentrations, in kidney organoids, characterized by podocyte detachment from the main organoid body. Moreover, no osmotic or toxicity effect was observed. Importantly, this phenotype resembles disease features identified in diabetic patients, where podocyte loss and detachment from the glomerular basement membrane is associated with pathophysiology. We identified a correlation between the injury phenotype, characterized by epithelial detachment, and proinflammatory cytokine upregulation, which is driven by high glucose, and we have shown it can be targeted therapeutically. Therefore, this new experimental model in-vitro offers up new insights into the pathophysiology of diabetes and its complications, and represents a new platform to screen for therapeutics.

#658 Analysis of cerebral blood volume and flow changes in ESRD patients undergoing hemodialysis using functional near-infrared spectroscopy

Abstract Background and Aims End stage renal disease (ESRD) patients undergoing hemodialysis experience diverse neurological complications. However, studies regarding how hemodialysis is related to these neurological problems are limited. This study investigated cerebral blood volume (CBV) and cerebral blood flow (CBF) during hemodialysis using functional near-infrared spectroscopy (fNIRS) to analyze cerebral hemodynamic changes. Method ESRD patients undergoing maintenance hemodialysis without a history of neurological disorders were enrolled prospectively. The fNIRS data were collected using a NIRSIT Lite device. The fNIRS values were recorded three times for each patient: before the start of hemodialysis (pre-HD), 1 h after the start of hemodialysis (mid-HD), and after the end of hemodialysis (post-HD). The average changes in oxy-hemoglobin (HbO2), deoxy-hemoglobin (HbR), total hemoglobin (HbT, calculated as HbO2 + HbR) concentrations, and in hemoglobin concentration difference (HbD, calculated as HbO2 – HbR) were analyzed. We then compared the differences in changes in HbO2, HbR, HbT, and HbD according to the hemodialysis period. Results Thirty hemodialysis patients were analyzed. Between the Pre-HD and Post-HD periods, there were significant differences in changes in HbO2 (0.005 ± 0.001 µM vs. 0.015 ± 0.004 µM, p=0.046) and HbT (0.006 ± 0.001 µM vs. 0.016 ± 0.008 µM, p=0.029). Additionally, between Pre-HD and Post-HD periods, HbD tended to increase; however, this was not statistically significant (0.005 ± 0.001 µM vs. 0.014 ± 0.004 µM, p=0.094). Conclusion We demonstrated that during one hemodialysis session, the relative change in CBV increased post-HD compared with pre-HD. These results are expected to help understand the mechanisms underlying the effects of hemodialysis on brain function.

#3050 Hemodynamic study of hypertensive disorders in pregnancy using cardiothoracic bioimpedance

Abstract Background and Aims Hypertensive disorders in pregnancy (HDP) are a major cause of maternal and perinatal morbidity and mortality. There is still a need for the development of biomarkers for early diagnosis of the severity of the condition. Thoracic electrical bioimpedance (TEB) is a non-invasive hemodynamic technique based on the resistance to the flow of electrical current. We investigated hemodynamic changes in pregnant/postpartum women with HDP using TEB. Method A retrospective observational study was conducted in pregnant and postpartum women with hypertension monitored by TEB. Indirect changes were analyzed in: cardiac work, left cardiac work index (LCWI kg⋅m/m2) and calculated cardiac output (CO ml/min=systolic volume -SV ml- × heart rate -HR bpm-); fluid status, thoracic fluid content index (TFCI l/kOhm/m2); and resistances, systemic vascular resistance index (SVRI dyn.s.cm-5.m2). Normality of variables was assessed by Shapiro-Wilk test and correlation analysis was performed by Pearson/Spearman tests. Statistical inference between the hypertension-preeclampsia and pregnancy-postpartum groups was performed using Student's/Mann-Whitney U tests. Analysis was performed using STATA 12. Results Fifty-five patients were included with a mean age of 36.5 years (SD 4.54), 69% were older than 35 years. Pregnant women accounted for 86% of the TEB evaluations, the majority (93.6%) in the third trimester. There was chronic hypertension in 7.27% and pre-eclampsia in 18.18% of previous pregnancies. The diagnoses were: pre-eclampsia (56.36%), gestational hypertension (40%) and HELLP syndrome (3.64%). The mean blood pressure was 144/89 (SD 16/11) mmHg. Mean proteinuria was 363.2 (range: 10.3-23220) mg/g. The median values were as follow: LCWI: 5.05 (IQR: 1.4) kg⋅m/m2; CO: 6352 (IQR: 2345) ml/min; TFCI: 17.9 (IQR: 6.3) l/kOhm/m2; SVRI: 2167.63 (SD: 462.87) dyn.s.cm-5.m2. LCWI showed a weak positive correlation with systolic blood pressure (SBP) and a strong correlation with diastolic blood pressure (DBP) (Rho 0.2899 and 0.5176, respectively). There was also a positive and moderate correlation between SVRI and SBP and DBP (r 0.4265 and 0.4019, respectively). There was no correlation between CO or TFCI and SBP or DBP. No statistically significant differences in hemodynamic parameters were found between gestational hypertension and pre-eclampsia, nor between pregnant and postpartum women. Conclusion Increased blood pressure in the setting of HDP correlates with increased LCWI and systemic resistance independent of fluid retention. An increase in systemic vascular resistance measured by TEB (which decreases in normal pregnancy) may be an early diagnostic marker of HDP. These findings require further validation in a larger cohort, including a control group of pregnant women without hypertension.

#412 Influence of SGLT2I on tubulointerstitium in DKD patients with moderate renal dysfunction

Abstract Background and Aims In the FAGOTTO study (jRCTs041200069) to evaluate changes of renal hemodynamics on initial glomerular filtration rate (GFR) dip induced by Sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients (pts) with type 2 diabetic kidney disease (DKD) and moderate renal dysfunction, we reported that SGLT2 inhibition maintained the levels of glomerular filtration fraction (FF) and renal vascular resistance (RVR) during decrease in GFR as well as renal plasma and blood flow. In this sub analysis, we evaluated if GFR dip by SGLT2i might induce tubulointerstitial disorder by measuring urinary biomarkers. Method The FAGOTTO study was a 12-week multicenter, open-label, randomized (1:1), parallel-group study treated with Canagliflozin (Group CA) or control groups (Group CO) in DKD pts with 30 ≤ estimated GFR (eGFR) ≤ 60 mL/min/1.73 m2. Urinary biomarkers including liver-type fatty-acid binding protein (L-FABP), N-acetyl-glucosaminidase (NAG), β2-microglobulin (β2MG) and monocyte chemoattractant protein-1 (MCP-1) were measured at baseline, 4 weeks and 12 weeks after start of the trial. The adjusted mean and SE for changes were calculated at each time point by a linear mixed model with baseline values, time point, and interaction of the treatment group as the fixed effects. We compared these changes between treatment the groups the Tukey-Kramer method to correct for multiplicity. Results The adjusted mean changes in L-FABP at the 4-week and 12-week time point after trial start were estimated −0.35 and −0.17 μg/gCr in Group CA and 0.06 and 1.23 μg/gCr in Group CO in a linear mixed model, respectively. Similarly, the changes were estimated 2.63 and 3.71 U/gCr in Group CA and 1.38 and −1.21 U/gCr in Group CO in NAG, 317.7 and 291.4 μg/gCr in Group CA and 416.6 and 375.1 μg/gCr in Group CO in β2MG and 19.6 and 64.6 pg/gCr in Group CA and −7.7 and −2.7 pg/gCr in Group CO in MCP-1, respectively. When compared the changes in L-FABP, NAG, β2MG and MCP-1 between Group Ca and Group Co by Tukey-Kramer multiple-comparison test, there were no significant differences in any biomarkers. (Figure). Conclusion In this analysis, no significant difference in any of these biomarkers was detected in Group CA compared to those in Group CO at 4 weeks and 12 weeks after administration of SGLT2i. Although further studies should be needed to conclude, transient decrease in GFR after administration of SGLT2i might not be involved with tubulointerstitial damage and our study gives one evidence as a safety information in use of SGLT2i to DKD pts with moderate renal dysfunction.