Search

Transplantation remains the preferred treatment for end‐stage kidney disease but is critically limited by the number of available organs. Xenografts from genetically modified pigs have become a promising solution to the loss of life while waiting for transplantation. However, the current clinical model for xenotransplantation will require off‐site procurement, leading to a period of ischemia during transportation. As of today, there is limited understanding regarding the preservation of these organs, including the duration of viability, and the associated molecular changes. Thus, our aim was to evaluate the effects of static cold storage (SCS) on α1,3‐galactosyltransferase knockout (GGTA1 KO) kidney. After SCS, viability was further assessed using acellular sub‐normothermic ex vivo perfusion and simulated transplantation with human blood. Compared to baseline, tubular and glomerular interstitium was preserved after 2 days of SCS in both WT and GGTA1 KO kidneys. Bulk RNA‐sequencing demonstrated that only eight genes were differentially expressed after SCS in GGTA1 KO kidneys. During sub‐normothermic perfusion, kidney function, reflected by oxygen consumption, urine output, and lactate production was adequate in GGTA1 KO grafts. During a simulated transplant with human blood, macroscopic and histological assessment revealed minimal kidney injury. However, GGTA1 KO kidneys exhibited higher arterial resistance, increased lactate production, and reduced oxygen consumption during the simulated transplant. In summary, our study suggests that SCS is feasible for the preservation of porcine GGTA1 KO kidneys. However, alternative preservation methods should be evaluated for extended preservation of porcine grafts. [ABSTRACT FROM AUTHOR]

• Cold ex situ lung perfusion (ESLP) has demonstrated improved preservation in small animal ESLP compared to normothermic ESLP and cold static preservation, but this has never been tested in a large animal model. • We investigated the effect of a range of cold perfusion temperatures over 12 hours of ESLP with transplantation assessment over a 4-hour period in 40- to 50-kg juvenile pigs. • Prolonged normothermic (38°C) NPV-ESLP is superior to 10, 20, and 32°C perfusion. • We also demonstrate the need to reduce perfusion flow rates in response to cold perfusion ESLP. Cold ex situ lung perfusion (ESLP) has demonstrated improved preservation in small animal ESLP compared to normothermic ESLP and cold static preservation. We hypothesized that cold negative pressure ventilation (NPV)-ESLP would improve graft function in a porcine transplantation model. Four perfusate temperatures were examined with 12 hours NPV-ESLP in a large animal transplantation model. Pig lungs were allotted to four groups: (1) Normothermia (38°C, n = 6); (2) profound hypothermia (10°C, n = 6); (3) moderate hypothermia (20°C, n = 3); (4) subnormothermia (32°C, n = 3). A fifth group subnormothermic low-flow (SNLF) perfusion was examined to assess the effect of reduced cardiac output with cold perfusion (32°C, 10% cardiac output, n = 6). Only Normothermic and SNLF groups demonstrated acceptable oxygenation after 12 hours NPV-ESLP and were transplanted. All other groups failed prematurely. After 12 hours of ESLP, Normothermic lungs demonstrated significantly greater dynamic compliance compared to SNLF lungs (P =.03). Edema formation post-ESLP was significantly worse in the SNLF group (P =.01). There was no significant difference in pulmonary artery pressures after ESLP (P =.10); however, pulmonary vascular resistance was significantly greater in the SNLF (P =.04). Isolated left lung oxygenation 4-hours post-transplant and left lung edema formation was not significantly different between Normothermic and SNLF post-transplant (P =.09). Proinflammatory cytokines were significantly greater during SNLF-ESLP (tumor necrosis factor alpha, P <.05). Prolonged normothermic (38°C) NPV-ESLP is superior to 10, 20, and 32°C perfusion. Normothermic ESLP of porcine lungs results in superior graft function and reduced inflammation versus SNLF-ESLP. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate the utility of cardiac magnetic resonance imaging to estimate the principle hemodynamic parameters that are measured by right heart catheterization in a noninvasive manner i.e. mean pulmonary artery pressure, pulmonary vascular resistance and pulmonary artery wedge pressure through cardiac magnetic resonance based numerical models. Materials and methods: 29 pulmonary hypertension patients, fitting the inclusion criteria were randomly selected and included in the study. CMR Imaging and right side heart catheter (RHC) were performed within one month. 3 Cardiac MRI based models in literature that showed high accuracy were tested. Two equations for mPAP calculation; mPAP=-231.423 + 53.8(loge inter-ventricular septal angle)+log10(right ventricular mass divided by left ventricular mass) i.e ventricular mass index X 8.708+area of pulmonary artery in diastole X 0.009 and mPAP = –4.6+(0.32*septal angle)+(ventricular mass index × 16.3). One equation for PAWP; PAWP = left atrial volume index +6.43 × 0.22. Results: The Altman and Bland correlation between mPAP invasively measured and CMR-estimated mPAP had good correlation with r= 0.594 and r =0.599 (P <0.001) for CMR based mPAP model 1 and 2, respectively. The calculated mean bias between the RHC-derived and CMR-estimated mPAP was 7.9 (agreement interval -24.8 to 40.6 mm Hg) and mean bias -3 (agreement interval -34.8 to 28.2 mm Hg) for CMR based mPAP model 1 and 2, respectively. There was no correlation between invasively measured and CMR-estimated PAWP with (P =0.092) for CMR based PAWP model. The mean bias between the RHC-derived and CMR-estimated PAWP was 2.4 (agreement interval –13.5 to 18.2 mm Hg). The correlation between invasively calculated and CMR-estimated PVR had good correlation with r =0.703 and r =0.704 (P <0.001) for CMR based PVR model 1 and 2, respectively. The mean bias between the RHC-measured and CMR-estimated mPAP was 0.6 (agreement interval -11.6 to 12.8 mm Hg) and mean bias -1.3 (agreement interval -12.1 to 9.5 mm Hg) for CMR based mPAP model 1 and 2, respectively. Conclusion: Our results showed good correlations between CMR findings and RHC as regard mPAP and PVR. Thus, estimation of mPAP, PAWP and PVR non-invasively using CMR is feasible but needs further studies to improve accuracy. [ABSTRACT FROM AUTHOR]

Introduction: The sympathetic nervous system and the renin-angiotensin system (RAS) are the most pivotal vasoactive systems in regulating renal hemodynamics. The main objective of this study was to determine the role of the angiotensin II (Ang II) type 1 receptor (AT1R) antagonist on renal hemodynamic responses to Ang 1-7 infusion in innervated and denervated male and female rats. Methods: Male and female Wistar rats underwent unilateral nephrectomy. Four weeks later, they were divided into two groups: innervated and acutely denervated groups. Subsequently, the anesthetized and catheterized rats in both groups were treated with saline as a vehicle and losartan infusion. Mean arterial pressure (MAP), renal blood flow (RBF), renal perfusion pressure (RPP), and renal vascular resistance (RVR) responses to Ang 1-7 (100, 300, and 1000 ng kg−1 min−1 ) were then measured at controlled RPP. Results: Basal MAP, RPP, RBF, and RVR did not show significant differences between the intact and denervated groups. Losartan significantly decreased MAP, RPP, and RVR in both innervated and denervated male and female rats (P<0.001), while RBF increased only in innervated and denervated female rats (P<0.004). However, following Ang 1-7 administration, the RBF response to Ang 1-7 infusion differed significantly between intact and denervated male rats treated with losartan (P<0.04). This response was not observed in female rats. Conclusion: These data suggest a synergistic effect of losartan and Ang 1-7 on increased RBF in the presence of renal sympathetic nerves in male rats. [ABSTRACT FROM AUTHOR]

Background: The purpose of the current study was to compare the color Doppler findings of uterine arteries and perinatal outcomes in pregnant women with and without previous cesarean section (C/S). Methods: This cohort study enrolled 308 pregnant women aged 20-35 without underlying diseases, with at least one previous pregnancy and childbirth. The participants were divided into two groups: 154 women without C/S and 154 women with C/S. Baseline data were collected, followed by uterine artery Doppler scans. Then, the perinatal outcomes, including pre-eclampsia, intrauterine growth restriction (IUGR), premature delivery, and birth weight were evaluated. Results: The average age of patients in the C/S group was 30.46±3.81, which was significantly higher than the non-C/S group (28.86±4.64). It was found that uterine artery resistance was higher in women with C/S history (1.11±0.44, p<0.001) compared to those without (1.00±0.37, p<0.001). Pre-eclampsia incidence was also higher in C/S group (16.1%, p=0.042) compared to non-C/S group (9.1%, p=0.042). The incidence of preterm birth in the C/S group (p=0.209), the incidence of IUGR (p= 0.791), and the average birth weight (p=0.291) in the two groups did not differ significantly. The average gestational age in the C/S group was 37.54±1.4, and in the non-C/S group was 38.01±1.99 weeks. The results were not affected by potential confounders such as age, the time interval between pregnancies, and also body mass index. Conclusion: Previous cesarean section can significantly increase the uterine artery resistance in subsequent pregnancy. [ABSTRACT FROM AUTHOR]

Aims The cytokine interleukin-6 (IL-6) plays a central role in the inflammation cascade as well as cardiovascular disease progression. Since myeloid cells are a primary source of IL-6 formation, we aimed to generate a mouse model to study the role of myeloid cell-derived IL-6 in vascular disease. Methods and results Interleukin-6-overexpressing (IL-6OE) mice were generated and crossed with LysM-Cre mice, to generate mice (LysM-IL-6OE mice) overexpressing the cytokine in myeloid cells. Eight- to 12-week-old LysM-IL-6OE mice spontaneously developed inflammatory colitis and significantly impaired endothelium-dependent aortic relaxation, increased aortic reactive oxygen species (ROS) formation, and vascular dysfunction in resistance vessels. The latter phenotype was associated with decreased survival. Vascular dysfunction was accompanied by a significant accumulation of neutrophils, monocytes, and macrophages in the aorta, increased myeloid cell reactivity (elevated ROS production), and vascular fibrosis associated with phenotypic changes in vascular smooth muscle cells. In addition to elevated Mcp1 and Cxcl1 mRNA levels, aortae from LysM-IL-6OE mice expressed higher levels of inducible NO synthase and endothelin-1, thus partially accounting for vascular dysfunction, whereas systemic blood pressure alterations were not observed. Bone marrow (BM) transplantation experiments revealed that vascular dysfunction and ROS formation were driven by BM cell-derived IL-6 in a dose-dependent manner. Conclusion Mice with conditional overexpression of IL-6 in myeloid cells show systemic and vascular inflammation as well as endothelial dysfunction. A decrease in circulating IL-6 levels by replacing IL-6-producing myeloid cells in the BM improved vascular dysfunction in this model, underpinning the relevant role of IL-6 in vascular disease. [ABSTRACT FROM AUTHOR]

Rationale: Rates of emphysema progression vary in chronic obstructive pulmonary disease (COPD), and the relationships with vascular and airway pathophysiology remain unclear. Objectives: We sought to determine if indices of peripheral (segmental and beyond) pulmonary arterial dilation measured on computed tomography (CT) are associated with a 1-year index of emphysema (EI; percentage of voxels <−950 Hounsfield units) progression. Methods: Five hundred ninety-nine former and never-smokers (Global Initiative for Chronic Obstructive Lung Disease stages 0–3) were evaluated from the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort: rapid emphysema progressors (RPs; n = 188, 1-year ΔEI > 1%), nonprogressors (n = 301, 1-year ΔEI ± 0.5%), and never-smokers (n = 110). Segmental pulmonary arterial cross-sectional areas were standardized to associated airway luminal areas (segmental pulmonary artery–to–airway ratio [PAARseg]). Full-inspiratory CT scan–derived total (arteries and veins) pulmonary vascular volume (TPVV) was compared with small vessel volume (radius smaller than 0.75 mm). Ratios of airway to lung volume (an index of dysanapsis and COPD risk) were compared with ratios of TPVV to lung volume. Results: Compared with nonprogressors, RPs exhibited significantly larger PAARseg (0.73 ± 0.29 vs. 0.67 ± 0.23; P = 0.001), lower ratios of TPVV to lung volume (3.21 ± 0.42% vs. 3.48 ± 0.38%; P = 5.0 × 10−12), lower ratios of airway to lung volume (0.031 ± 0.003 vs. 0.034 ± 0.004; P = 6.1 × 10−13), and larger ratios of small vessel volume to TPVV (37.91 ± 4.26% vs. 35.53 ± 4.89%; P = 1.9 × 10−7). In adjusted analyses, an increment of 1 standard deviation in PAARseg was associated with a 98.4% higher rate of severe exacerbations (95% confidence interval, 29–206%; P = 0.002) and 79.3% higher odds of being in the RP group (95% confidence interval, 24–157%; P = 0.001). At 2-year follow-up, the CT-defined RP group demonstrated a significant decline in postbronchodilator percentage predicted forced expiratory volume in 1 second. Conclusions: Rapid one-year progression of emphysema was associated with indices indicative of higher peripheral pulmonary vascular resistance and a possible role played by pulmonary vascular–airway dysanapsis. [ABSTRACT FROM AUTHOR]

Since the heart and blood network are the most delicate and dangerous organs in a living organism, the cardiovascular system is the most complex system overall. The number of patients has been steadily rising due to the disorders it causes, and in recent years, the instability of this system has been responsible for the greatest proportion of deaths globally. Therefore, a prior understanding of the cardiovascular system's function and the search for its abnormalities are required to develop methods that can detect the disease at an early stage and identify the most effective treatments. Sensitivity analysis-based mathematical modelling is a helpful tool for assessing and forecasting this system, enabling the development of mitigation techniques for these disruptions. This paper aims to define the concept of sensitivity analysis (SA) and use this theory to analyses five parameters of the dynamic cycle of both pulse pressure (PP) and mean arterial pressure (Pm). These parameters are: 1) stroke volume (ΔV), 2) peripheral resistance (R), 3) heart rate (T), 4) ejection period (The), and 5) arterial compliance (C), to determine the most important factor that affects both mean arterial pressure and pulse pressure to control heart and stroke diseases. By creating a condensed laboratory model that represented a patient without hypertension and simulating the cardiovascular system using the necessary mathematical formulas, this was possible. The test results showed that stroke volume and arterial compliance were the main factors that most affected pulse pressure. Mean arterial pressure, stroke volume, and total circumferential resistance of the artery wall were the two most principal factors. The reasons were explained in more detail in the practical aspect of this paper. Illustrative graphs will also support these findings. In the end, this topic will be discussed in a medical manner by presenting ways to control both pulse pressure, mean arterial pressure, and reduce the occurrence of heart attacks and strokes. [ABSTRACT FROM AUTHOR]

Renal and genitourinary ultrasound are fundamental resources employed by emergency and critical care healthcare providers to make prompt diagnoses and perform ultrasound-guided procedures. At the bedside, ultrasound can aid in the diagnosis of relevant pathologies, such as post-renal obstruction or kidney stones, and life-threatening conditions such as aortic dissection or hemoperitoneum. A narrative overview was performed, providing an updated review of renal and genitourinary ultrasound for emergency and critical care healthcare providers, emphasizing its advantages and the latest advances in the field. A thorough summary that can be utilized as a guide for emergency and critical care healthcare providers is presented. The daily hemodynamic management of critically ill patients involves the implementation of new protocols, such as VexUS or the evaluation of the renal resistance index. The role of ultrasound in managing acute nephropathy and genitourinary issues is increasingly crucial given its bedside availability, thus this imaging modality not only facilitates the initiation of therapeutic interventions but also provides swift prognostic insights that are vital to provide tailored patient care. As further advances in ultrasound will arise, it is important for healthcare providers to foster the use of these technologies capable of improving patient outcomes. [ABSTRACT FROM AUTHOR]

One of the reasons of the development of pathologies causing death is hypoxia. The purposes of this study were (1) to study some physiological and biochemical mechanisms of α2-adrenoblockers, which ensure the tissue resistance increase to hypoxia; (2) to offer new drugs contributing to the increase of tissues' stability towards the hypoxic affection; and (3) to submit new medications to surpass by their anti-hypoxic activity of those already used in modern medicine and have some advantages. The reactivity of postsynaptic vascular α2-adrenoceptors was determined on the damaged spinal cord expressed by the blood pressure increase in response to intravenous administration of azepexole that selectively binds to α2-adrenoceptors. Determination of the systemic hemodynamic values and the vascular resistance to the blood flow was performed by the method with plastic microspheres of marked isotopes. pO2 in the blood and the oxygen-transporting function were determined in a sample of 0.1 ml of blood in 30, 90, and 180 min after the α2-adrenoblockers' injections. It has been found that one of the major hemodynamic effects of mesedin and beditin was an improvement in cardiac output, as well as a prolonged increase in coronary blood flow and vasodilation of the heart vessels. Some anti-hypoxic mechanisms of the studied α2-adrenoblockers are an improvement of blood oxygen-transporting function followed by tissue oxygenation and the increased level of corticosterone and resistance to hypoxia. Revealing the mechanisms of action of the postsynaptic α2-adrenoceptors suggests that mesedin and beditin are potentially effective therapeutic means for many hypoxic conditions. [ABSTRACT FROM AUTHOR]

Background: Atrial septal defects (ASD) are the most common type of adult congenital heart disease (ACHD) associated with a high risk developing of pulmonary arterial hypertension (PAH). ASD closure is not recommended in patients with PAH and Pulmonary Vascular Resistance (PVR) ≥ 5 Wood Unit (WU). Noninvasive methods have been proposed to measure PVR; however, their accuracy remains low. Right Ventricle (RV) - Pulmonary Artery (PA) coupling is defined as the ability of the RV to adapt to high-resistance conditions. Tricuspid Annular Plane Systolic Excursion (TAPSE)/estimated pulmonary artery systolic pressure (ePASP) calculation using echocardiography is a noninvasive technique that has been proposed as a surrogate equation to evaluate RV-PA coupling. Currently, no research has demonstrated a relationship between RV-PA coupling and PVR in patients with ASD. Methods: The study participants were consecutive eligible patients with ASD who underwent right heart catheterization (RHC) and echocardiography at Hasan Sadikin General Hospital, Bandung. Both the procedures were performed on the same day. RV-PA Coupling, defined as TAPSE/ePASP > 0.31, was assessed using echocardiography. The PVR was calculated during RHC using the indirect Fick method. Results: There were 58 patients with ASD underwent RHC and echocardiography. Among them, 18 had RV/PA Coupling and 40 had RV/PA Uncoupling. The PVR values were significantly different between the two groups (p = 0.000). Correlation test between TAPSE/ePASP with PVR showed moderate negative correlation (r= -0.502, p = 0.001). TAPSE/ePASP ≤ 0.34 is the cutoff point to predict PVR > 5 WU with sensitivity of 91.7% and specificity 63.6%. Conclusion: This study showed a moderate negative correlation between TAPSE/ePASP and PVR. TAPSE/ePASP ≤ 0.34 could predict PVR > 5 WU with good sensitivity. [ABSTRACT FROM AUTHOR]

Background: In intracranial pathologic conditions of intracranial pressure (ICP) disturbance or hemodynamic instability, maintaining appropriate ICP may reduce the risk of ischemic brain injury. The change of ICP is often accompanied by the change of intracranial blood status. As a non-invasive functional imaging technique, the sensitivity of electrical impedance tomography (EIT) to cerebral hemodynamic changes has been preliminarily confirmed. However, no team has conducted a feasibility study on the dynamic detection of ICP by EIT technology from the perspective of non-invasive whole-brain blood perfusion monitoring. In this study, human brain EIT image sequence was obtained by in vivo measurement, from which a variety of indicators that can reflect the tidal changes of the whole brain impedance were extracted, in order to establish a new method for non-invasive monitoring of ICP changes from the level of cerebral blood perfusion monitoring. Methods: Valsalva maneuver (VM) was used to temporarily change the cerebral blood perfusion status of volunteers. The electrical impedance information of the brain during this process was continuously monitored by EIT device and realtime imaging was performed, and the hemodynamic indexes of bilateral middle cerebral arteries were monitored by transcranial Doppler (TCD). The changes in monitoring information obtained by the two techniques were compared and observed. Results: The EIT imaging results indicated that the image sequence showed obvious tidal changes with the heart beating. Perfusion indicators of vascular pulsation obtained from EIT images decreased significantly during the stabilization phase of the intervention (PAC: 242.94 ± 100.83, p < 0.01); perfusion index which reflects vascular resistance increased significantly in the stable stage of intervention (PDT: 79.72 ± 18.23, p < 0.001). After the intervention, the parameters gradually returned to the baseline level before compression. The changes of EIT indexes in the whole process are consistent with the changes of middle cerebral artery velocity related indexes shown in TCD results. Conclusion: The EIT image combined with the blood perfusion index proposed in this paper can reflect the decrease of cerebral blood flow under the condition of increased ICP in real time and intuitively. With the advantages of high time resolution and high sensitivity, EIT provides a new idea for non-invasive bedside measurement of ICP. [ABSTRACT FROM AUTHOR]

Objective: To compare the cardiopulmonary effects of apneustic anesthesia ventilation (AAV) and conventional mechanical ventilation (CMV) in anesthetized pigs and to describe a new mode of ventilation for anesthetized veterinary species. Study design: Randomized, crossover design without washout. Animals: Twelve healthy, female white Landrace pigs. Methods: Following ketamine-midazolam premedication and anesthetic induction with propofol, the trachea was intubated, and each pig was positioned in dorsal recumbency. Anesthesia was maintained with propofol and sufentanil infusions. Pigs were instrumented and their lungs were sequentially ventilated with each mode, in random order, for 1 h according to predefined criteria [fraction of inspired oxygen (FiO2) = 0.21, 10mL kg-1 tidal volume (VT), and arterial carbon dioxide tension (PaCO2) within 40-45 mmHg]. Cardiopulmonary data were collected at baseline, 30 and 60min. In 8 pigs, thoracic computed tomography (CT) was performed following the 60min time point for each mode of ventilation and images were analyzed to quantify lung aeration. The effects of ventilation mode, time, and order were analyzed using repeated measures ANOVA. Paired t-tests were used to compare lung aeration between modes. Significance was defined as p < 0.05. Results: Data from12 pigs were analyzed. A significant effect of mode was found for heart rate, mean arterial pressure (MAP), pulmonary artery occlusion pressure, cardiac index (CI), stroke volume index, systemic vascular resistance, pulmonary vascular resistance, oxygen delivery index (DO2I), oxygen extraction ratio (O2ER), VT, arterial oxygen tension, arterial hemoglobin saturation, PaCO2, end-tidal carbon dioxide tension, alveolar dead space (VDalv/VTalv), venous admixture (Qs/Qt), mean airway pressure, and dynamic compliance index (CRSI). Order effects were also observed for some cardiovascular and respiratory variables. For the eight pigs that underwent thoracic CT, AAV resulted in significantly larger proportions of normally and hyperaerated lung while CMV resulted in larger proportions of hypoaerated and atelectatic lung. Conclusions: In dorsally recumbent anesthetized pigs, ventilated with FiO2 = 0.21, both modes of ventilation supported adequate oxygenation while AAV resulted in higher CRSI, and lower VDalv/VTalv and Qs/Qt, compared with CMV. AAV was also associated with lower MAP, CI, and DO2I and higher O2ER compared with CMV. Further investigation of AAV in anesthetized animals is warranted. [ABSTRACT FROM AUTHOR]

Background. The Impella 5.5 offers a less invasive transvalvular approach to left ventricular mechanical support. End‐organ recovery and hemolysis have been well‐studied with durable left ventricular assist devices but effects of Impella 5.5 on these parameters are less well described. Methods. All Impella 5.5 recipients between August 2020 and June 2023 were reviewed from a single institution. Hemodynamics and laboratory values were compared between preimplant and prior to device removal. Hemolysis was defined as postoperative lactate dehydrogenase >1000 IU/L with concurrent plasma‐free hemoglobin >50 mg/dL. Paired Wilcoxon tests compared the median of differences between preimplant and pre‐explant values. Results. We studied 127 consecutive implants of the Impella 5.5. Thirty‐one patients had concomitant VA‐ECMO, and one received Impella 5.5 after durable LVAD explant; these cases were excluded. Our final cohort included 95 patients, with an average age of 55.29 ± 14.5 years. Median implant duration was 11 days (IQR:6–16 days). To avoid confounding hemodynamic factors, we restricted hemodynamic analysis to the 37 patients who received isolated Impella 5.5, excluding those with prior IABP, Impella CP, acute MI, or prior cardiac surgery. These patients experienced improvements from baseline in pulmonary vascular resistance (−77.03 dynes/sec/cm−5, p < 0.01) and wedge pressure (−6.5 mmHg, p < 0.01). Furthermore, cardiac index improved from baseline (+1.3, p < 0.01). In the total cohort (n = 95), pre‐explant creatinine (−0.2 mg/dL, p < 0.01) and ALT (−9.0 mg/dL, p < 0.01) decreased relative to values before the implant. Twenty‐three (24%) met criteria for hemolysis; however, none underwent device removal for clinically significant hemolysis. Takeback was required in 25 patients, 22 of which were for axillary hematoma. Conclusions. Impella 5.5 support acutely improved markers of end‐organ function and hemodynamics, including PVR. [ABSTRACT FROM AUTHOR]

Large‐volume therapeutic phlebotomy is the mainstay of hemochromatosis treatment and offers an opportunity to investigate the hemodynamic changes during acute hypovolemia. An otherwise healthy 64‐year‐old male with hemochromatosis participated. On nine separate visits, 1000 mL therapeutic phlebotomy was performed. On one occasion, pre‐ and post‐phlebotomy orthostatic challenge with 27° reverse Trendelenburg position was administered. Mean arterial pressure, heart rate, and stroke volume were measured continuously during the procedures. The patient's tolerance to the interventions was continuously evaluated. The procedures were well tolerated by the patient. Mean arterial pressure was maintained during hemorrhage and following phlebotomy in both supine and reverse Trendelenburg positions, primarily through an increase in heart rate and systemic vascular resistance. The present study found that 1000 mL therapeutic phlebotomy in a patient with hemochromatosis may be acceptably and safely used to model hemorrhage. The approach demonstrates high clinical applicability and ethically robustness in comparison with volunteer studies. [ABSTRACT FROM AUTHOR]

Hypertensive disorders in pregnancy (HDP) are the most prevalent diseases during pregnancy. In addition to the already identified risk factors, exposure to environmental contaminants has been also considered a new one. Phthalates, which are classified as priority environmental pollutants due to their ubiquitousness and endocrine disrupting properties, have been implicated in HDP in some epidemiological studies. Nevertheless, phthalates' vascular impacts still need to be clarified. Thus, we aimed to understand the connection between phthalates exposure and the occurrence of gestational hypertension, as well as the pathway involved in the pathological vascular effects. We investigated diethyl phthalate's (DEP) effect on the vascular reactivity of the human umbilical arteries (HUAs) from normotensive and hypertensive pregnant women. Both DEP's nongenomic (within minutes effect) and genomic (24 h exposure to DEP) actions were evaluated, as well as the contribution of cyclic guanosine monophosphate and Ca2+ channel pathways. The results show that short-term exposure to DEP interferes with serotonin and histamine receptors, while after prolonged exposure, DEP seems to share the same vasorelaxant mechanism as estrogens, through the NO/sGC/cGMP/PKG signaling pathway, and to interfere with the L-type Ca2+ channels. Thus, the vascular effect induced by DEP is similar to that observed in HUA from hypertensive pregnancies, demonstrating that the development of HDP may be a consequence of DEP exposure. [ABSTRACT FROM AUTHOR]

The progress in research on the physiology of the cardiovascular system made in the last 100 years allowed for the development of the pathogenesis not only of secondary forms of hypertension but also of primary hypertension. The main determinants of blood pressure are described by the relationship between stroke volume, heart rate, peripheral resistance, and arterial stiffness. The theories developed by Guyton and Folkow describe the importance of the volume factor and total peripheral resistance. However, none of them fully presents the pathogenesis of essential hypertension. The multifactorial model of primary hypertension pathogenesis developed by Irving Page in the 1940s, called Page's mosaic, covers most of the pathophysiological phenomena observed in essential hypertension. The most important pathophysiological phenomena included in Page's mosaic form a network of interconnected "nodes". New discoveries both from experimental and clinical studies made in recent decades have allowed the original Page mosaic to be modified and the addition of new pathophysiological nodes. Most of the clinical studies confirming the validity of the multifactorial pathogenesis of primary hypertension concern adults. However, hypertension develops in childhood and is even perinatally programmed. Therefore, the next nodes in Page's mosaic should be age and perinatal factors. This article presents data from pediatric clinical trials describing the most important pathophysiological processes associated with the development of essential hypertension in children and adolescents. [ABSTRACT FROM AUTHOR]

We studied changes of pulmonary microhemodynamics when modeling pulmonary artery thromboembolism on perfused isolated rabbit lungs after pretreatment with ranolazine and ivabradine. The increase in pulmonary artery pressure, pulmonary vascular resistance, and pre- and postcapillary resistance was less pronounced than in control animals, but was close to that in case of pulmonary thromboembolism after pretreatment with voltage-gated Na+ channel blockers lidocaine and ropivacaine. The increase of capillary filtration coefficient inversely correlated with values of capillary hydrostatic pressure. Thus, ranolazine and ivabradine exhibit the properties of voltage-gated Na+ channel blockers mainly in smooth muscles of pulmonary arterial vessels and promote the decrease in endothelial permeability. [ABSTRACT FROM AUTHOR]

NOTCH3 receptor signaling has been linked to the regulation of smooth muscle cell proliferation and the maintenance of smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension (World Health Organization Group 1 idiopathic disease: PAH) is a fatal disease characterized clinically by elevated pulmonary vascular resistance caused by extensive vascular smooth muscle cell proliferation, perivascular inflammation, and asymmetric neointimal hyperplasia in precapillary pulmonary arteries. In this review, a detailed overview of the specific role of NOTCH3 signaling in PAH, including its mechanisms of activation by a select ligand, downstream signaling effectors, and physiologic effects within the pulmonary vascular tree, is provided. Animal models showing the importance of the NOTCH3 pathway in clinical PAH will be discussed. New drugs and biologics that inhibit NOTCH3 signaling and reverse this deadly disease are highlighted. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the effects of a child-specific school-based high-intensity interval training (HIIT) implemented into physical education (PE) classes on various hemodynamic parameters and heart rate variability indices. Forty-six students (age 11 ± 1 year) were randomized into an intervention (INT n = 22) and a control group (CON n = 24). During a 12-week period, the INT and CON groups participated in regular PE twice weekly (45-90 minutes). The INT group received HIIT during the first 20 minutes of the 2 PE classes. Systolic and diastolic blood pressure, total peripheral resistance, aortic pulse wave velocity (aPWV), heart rate, SD of normal to normal heartbeat intervals, the root mean square of successive differences between normal heartbeats (RMSSD), the proportion of differences between adjacent normal to normal heartbeat intervals of more than 50 ms, low-frequency power, high-frequency power, and the LF/HF ratio were assessed before and after the experimental period. A p value ≤0.05 was considered statistically significant. Forty students (20 INT; 20 CON) were included in the analysis. A significant time x group interaction was detected for aPWV(p = 0.05, η² = 0.099), RMSSD (p = 0.010, η² = 0.161), low-frequency power (p = 0.009, η² = 0.165), high-frequency power (p < 0.001, η² = 0.272), and the LF/HF ratio (p < 0.001, η² = 0.354). The INT group revealed significant improvements for the respective parameters. School-based HIIT can induce improvements in cardiovascular parameters. These results highlight the potential of embedding HIIT within the school setting, offering a time-efficient exercise intervention. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition with heterogeneous outcomes difficult to predict at the individual level. Feared complications of advanced MASLD are linked to clinically significant portal hypertension and are initiated by functional and mechanical changes in the unique sinusoidal capillary network of the liver. Early sinusoidal vasoregulatory changes in MASLD lead to increased intrahepatic vascular resistance and represent the beginning of portal hypertension. In addition, the composition and function of gut microbiota in MASLD are distinctly different from the healthy state, and multiple lines of evidence demonstrate the association of dysbiosis with these vasoregulatory changes. The gut microbiota is involved in the biotransformation of nutrients, production of de novo metabolites, release of microbial structural components, and impairment of the intestinal barrier with impact on innate immune responses, metabolism, inflammation, fibrosis, and vasoregulation in the liver and beyond. The gut–liver axis is a conceptual framework in which portal circulation is the primary connection between gut microbiota and the liver. Accordingly, biochemical and hemodynamic attributes of portal circulation may hold the key to better understanding and predicting disease progression in MASLD. However, many specific details remain hidden due to limited access to the portal circulation, indicating a major unmet need for the development of innovative diagnostic tools to analyze portal metabolites and explore their effect on health and disease. We also need to safely and reliably monitor portal hemodynamics with the goal of providing preventive and curative interventions in all stages of MASLD. Here, we review recent advances that link portal metabolomics to altered sinusoidal vasoregulation and may allow for new insights into the development of portal hypertension in MASLD. [ABSTRACT FROM AUTHOR]

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease characterized by thrombotic occlusion of pulmonary arteries and vasculopathy, leading to increased pulmonary vascular resistance and progressive right‐sided heart failure. Thrombotic lesions in CTEPH contain CD68+ macrophages, and increasing evidence supports their role in disease pathogenesis. Macrophages are classically divided into pro‐inflammatory M1 macrophages and anti‐inflammatory M2 macrophages, which are involved in wound healing and tissue repair. Currently, the phenotype of macrophages and their localization within thrombotic lesions of CTEPH are largely unknown. In our study, we subclassified thrombotic lesions of CTEPH patients into developing fresh thrombi (FT) and organized thrombi (OT), based on the degree of fibrosis and remodeling. We used multiplex immunofluorescence histology to identify immune cell infiltrates in thrombotic lesions of CPTEH patients. Utilizing software‐assisted cell detection and quantification, increased proportions of macrophages were observed in immune cell infiltrates of OT lesions, compared with FT. Strikingly, the proportions with a CD206+INOS− M2 phenotype were significantly higher in OT than in FT, which mainly contained unpolarized macrophages. Taken together, we observed a shift from unpolarized macrophages in FT toward an expanded population of M2 macrophages in OT, indicating a dynamic role of macrophages during CTEPH pathogenesis. [ABSTRACT FROM AUTHOR]

Aims: In pulmonary arterial hypertension (PAH), upfront combination therapy with ERA and PDE5i is associated with a reduction in morbidity and mortality events and improves standard haemodynamics, but data remain limited. Aims of this study were (i) to capture detailed haemodynamic effects of rapid sequential dual combination therapy in patients with newly diagnosed PAH; (ii) to monitor the impact of treatment initiation on clinical variables and patients' risk status, and (iii) to compare the treatment effect in patients with 'classical PAH' and 'PAH with co‐morbidities'. Methods: Fifty patients (median age 57 [42–71] years, 66% female) with newly diagnosed PAH (76% idiopathic) were treated with a PD5i/sGC‐S or ERA, followed by addition of the respective other drug class within 4 weeks. All patients underwent repeat right heart catheterization (RHC) during early follow‐up. Results: At early repeat RHC (7 ± 2 months), there were substantial reductions in mean pulmonary artery pressure (mPAP: 52.2 ± 13.5 to 39.0 ± 10.6 mmHg; −25.3%), and pulmonary vascular resistance (PVR: 12.1 ± 5.7 to 5.8 ± 3.1 WU; −52.1%), and an increase in cardiac index (2.1 ± 0.4 to 2.7 ± 0.7 mL/min/m2; +32.2%) (all P < 0.05). Haemodynamic improvements correlated with improved clinical parameters including 6‐min walking distance (336 ± 315 to 389 ± 120 m), NTproBNP levels (1.712 ± 2.024 to 506 ± 550 ng/L, both P < 0.05) and WHO‐FC at 12 months, resulting in improved risk status, and were found in patients with few (n = 37) or multiple cardiovascular co‐morbidities (BMI > 30 kg/m2, hypertension, diabetes, coronary artery disease [≥3]; n = 13), albeit baseline PVR in PAH patients with multiple co‐morbidities was lower (9.3 ± 4.4 vs. 13.1 ± 5.9 WU) and PVR reduction less pronounced compared with those with few co‐morbidities (−42.7% vs. −54.7%). However, comprehensive haemodynamic assessment considering further variables of prognostic relevance such as stroke volume index and pulmonary artery compliance showed similar improvements among the two groups (SVI: +50.0% vs. +49.2%; PAC: 91.7% vs. 100.0%). Finally, the 4‐strata risk assessment approach was better able to capture treatment response as compared with other approaches, particularly in patients with co‐morbidities. Conclusions: Rapid sequential combination therapy with PDE5i/sGC‐S and ERA substantially ameliorates cardiopulmonary haemodynamics at early follow‐up in patients without, and to a lesser extent, with cardiovascular co‐morbidities. This occurs in line with improvements of clinical parameters and risk status. [ABSTRACT FROM AUTHOR]

Intradialytic hypotension (IDH) is a severe complication of hemodialysis (HD) with a significant impact on morbidity and mortality. In this study, we used a wearable device for the continuous monitoring of hemodynamic vitals to detect hemodynamic changes during HD and attempted to identify IDH. End-stage kidney disease patients were continuously monitored 15 min before starting the session and until 15 min after completion of the session, measuring heart rate (HR), noninvasive cuffless systolic and diastolic blood pressure (SBP and DBP), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR). Data were analyzed retrospectively and included comparing BP measured by the wearable devices (recorded continuously every 5 s) and the cuff-based devices. A total of 98 dialysis sessions were included in the final analysis, and IDH was identified in 22 sessions (22.5%). Both SBP and DBP were highly correlated (r > 0.62, p < 0.001 for all) between the wearable device and the cuff-based measurements. Based on the continuous monitoring, patients with IDH had earlier and more profound reductions in SBP and DBP during the HD treatment. In addition, nearly all of the advanced vitals differed between groups. Further studies should be conducted in order to fully understand the potential of noninvasive advanced continuous monitoring in the prediction and prevention of IDH events. [ABSTRACT FROM AUTHOR]

In recent decades, there has been considerable effort in investigating the clinical utility of renal Doppler measurements in both cardiovascular and renal disorders. In particular, a measure of renal arterial resistance, the renal resistive index (RRI), has been demonstrated to predict chronic kidney disease progression and acute kidney injury in different clinical settings. Furthermore, it is linked to a poorer prognosis in individuals suffering from chronic heart failure. Examining the renal venous flow through pulsed Doppler can offer additional insights into renal congestion and cardiovascular outcomes for these patients. This review seeks to summarize the existing data concerning the clinical significance of arterial and venous renal Doppler measurements across various cardiovascular and renal disease contexts. [ABSTRACT FROM AUTHOR]

Objective: To examine potential alterations in maternal cardiovascular parameters in hypertensive pregnancies with or without fetal growth restriction (FGR) in comparison to uncomplicated normotensive pregnancies, and to determine the correlation between maternal cardiovascular parameters and changes in umbilical and uterine artery circulation. Materials and methods: This study enrolled 73 pregnant women starting from the 20th week of gestation, categorized into three groups: hypertensive conditions (pregnancy-induced hypertension, preeclampsia or eclampsia, n = 30), hypertensive conditions with FGR (n = 8) and a control group of healthy normotensive pregnant women (n = 35). All participants underwent echocardiography to assess cardiac output and calculate peripheral vascular resistance. Additionally, fetal biometric measurements and Doppler ultrasound examinations of the uterine and umbilical artery were performed. The results were standardized into gestational age-adjusted z-scores. Results: The mean pulsatility index (PI) of the uterine artery (1.36, p

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by high mean pulmonary arterial pressure (≥ 20 mmHg) and remodeling of the vascular arteries. Approved therapies improve symptoms and delay clinical worsening in the long term, but they do not relieve acute exertional symptoms. RT234, a drug/device combination (Respira Therapeutics, Palo Alto, CA, USA) that delivers the phosphodiesterase 5 inhibitor vardenafil to the lungs via inhalation, has been shown to reduce pulmonary vascular resistance in patients with PAH. This study aims to evaluate whether RT234 can increase oxygen capacity during cardiopulmonary exercise testing (CPET) in patients with PAH. METHODS: This prospective, multi-center, open-label, two-cohort, dose-escalation, phase IIb trial in patients with PAH will evaluate the safety and efficacy of RT234 in improving exercise parameters. The trial began in September 2020 and is expected to be completed by early 2024. Patients eligible for enrollment will have a right heart catheterization-confirmed diagnosis of PAH, a 6-minute walking distance of ≥ 150 m, a minute ventilation/carbon dioxide production slope of ≥ 36, and will be on up to three stable oral and/or inhaled (not parenteral) PAH-specific background therapies. The estimated sample size is 86 patients, who will be divided into two dose cohorts. Cohort 1 will receive 0.5 mg RT234, and cohort 2 will receive 1.0 mg RT234. Each cohort will contain two subgroups based on the number of PAH background medications (up to two vs three). The trial will assess patients changes from baseline in peak oxygen consumption (VO2) during CPET 30 minutes after a single dose of 0.5 mg or 1.0 mg RT234, the change in the 6-minute walking distance, and the pharmacokinetics and safety profile of single doses of RT234. CONCLUSION: This is the first trial involving an as-needed medication for PAH. The trial will provide insights into the safety and efficacy of as-needed RT234 in treating the acute symptoms of PAH during exercise and will inform the design of further trials. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT04266197.

Abstract Computational fluid dynamics (CFD) has been utilized to calculate hemodynamic parameters in anterior communicating artery aneurysm (AComA), which is located at a junction between left and right A1 and A2 segments. However, complete or half circle of Willis (CoW) models are used indiscriminately. This study aims to suggest recommendations for determining suitable CoW model. Five patient-specific CoW models with AComA were used, and each model was divided into complete, left-half, and right-half models. After validating the CFD using a flow experiment, the hemodynamic parameters and flow patterns in five AComAs were compared. In four out of five cases, inflow from one A1 side had a dominant influence on the AComA, while both left and right A1 sides affected the AComA in the remaining case. Also, the average difference in time-averaged wall shear stress between the complete and half models for four cases was 4.6%, but it was 62% in the other case. The differences in the vascular resistances of left and right A1 and A2 segments greatly influenced the flow patterns in the AComA. These results may help to enhance clinicians’ understanding of blood flow in the brain, leading to improvements in diagnosis and treatment of cerebral aneurysms.

The article discusses the anesthesia management of a 30-year-old pregnant patient with severe post-rheumatic mitral stenosis undergoing a cesarean section. The patient was stabilized pharmacologically and underwent a cesarean section under general anesthesia, followed by percutaneous mitral commissurotomy two weeks later. The patient's hemodynamic stability was maintained during the surgery, and she was discharged without complications after the procedure. The article emphasizes the importance of a multidisciplinary approach and careful planning for safe delivery in such challenging cases. [Extracted from the article]

Marfan syndrome is a connective tissue disorder that affects multiple organs, with the most serious complications occurring in the cardiovascular system. Aortic root dilatation and dissection are particularly concerning. While the prevalence of Marfan syndrome is equal between genders, male patients have a higher risk of developing thoracic aortic aneurysm and dissection compared to females. A recent study using a mouse model of severe Marfan syndrome found that male mice had poorer survival rates and exhibited lower elastin content and more fragmented elastic fibers compared to female mice. The study suggests that material properties, aortic size, and wall integrity may be connected to dissection risk. Further research is needed to understand how age and sex contribute to dissection risk in Marfan syndrome. [Extracted from the article]

The article discusses the challenges faced by clinicians when determining the optimal ventilator settings for patients with acute respiratory distress syndrome (ARDS). The article explains that ARDS causes both lung stiffness and increased dead space, leading to difficulties in maintaining lung volume and oxygenation. The authors propose the use of positive end-expiratory pressure (PEEP) to recruit collapsed alveoli and minimize overdistention, but note that the effectiveness of PEEP varies among patients. The study suggests that personalized PEEP settings based on an assessment of recruitability may be beneficial in managing ARDS. However, the article acknowledges that further research is needed to determine the optimal PEEP and its impact on lung-protective ventilation and outcomes. [Extracted from the article]

End-stage heart failure due to left ventricular noncompaction (LVNC) poses unique challenges for ventricular assist device implantation, like inflow cannula obstruction due to trabeculations. We report a case of an 11-year-old boy with LVNC who underwent successful HeartWare implantation as a bridge to transplant for high pulmonary vascular resistance and had successful heart transplantation after 4 years of HeartWare support. [ABSTRACT FROM AUTHOR]

Background Systemic vascular resistance (SVR) is an integral component of the hemodynamic profile. Previous studies have demonstrated a close correlation between an estimated SVR analog (eSVR) based on echocardiographic methods and SVR by direct hemodynamic measurement. However, the prognostic impact of eSVR remains unestablished. Methods and Results Study participants with established coronary artery disease from the Heart and Soul Study formed this study cohort. We defined Doppler-derived eSVR as the ratio of systolic blood pressure to left ventricular outflow tract velocity time integral. Study participants were separated based on baseline eSVR tertile:

Introduction: The pulmonary endothelium is the primary target of lung ischemia-reperfusion injury leading to primary graft dysfunction after lung transplantation. We hypothesized that treating damaged rat lungs by a transient heat stress during ex-vivo lung perfusion (EVLP) to elicit a pulmonary heat shock response could protect the endothelium from severe reperfusion injury. Methods: Rat lungs damaged by 1h warm ischemia were reperfused on an EVLP platform for up to 6h at a constant temperature (T°) of 37°C (EVLP37°C group), or following a transient heat stress (HS) at 41.5°C from 1 to 1.5h of EVLP (EVLPHS group). A group of lungs exposed to 1h EVLP only (pre-heating conditions) was added as control (Baseline group). In a first protocol, we measured lung heat sock protein expression (HSP70, HSP27 and Hsc70) at selected time-points (n=5/group at each time). In a second protocol, we determined (n=5/group) lung weight gain (edema), pulmonary compliance, oxygenation capacity, pulmonary artery pressure (PAP) and vascular resistance (PVR), the expression of PECAM-1 (CD31) and phosphorylation status of Src-kinase and VE-cadherin in lung tissue, as well as the release in perfusate of cytokines (TNFα, IL-1β) and endothelial biomarkers (sPECAM, von Willebrand Factor -vWF-, sE-selectin and sICAM-1). Histological and immunofluorescent studies assessed perivascular edema and formation of 3-nitrotyrosine (a marker of peroxinitrite) in CD31 lung endothelium. Results: HS induced an early (3h) and persisting expression of HSP70 and HSP27, without influencing Hsc70. Lungs from the EVLP37°C group developed massive edema, low compliance and oxygenation, elevated PAP and PVR, substantial release of TNFα, IL-1β, s-PECAM, vWF, E-selectin and s-ICAM, as well as significant Src-kinase activation, VE-cadherin phosphorylation, endothelial 3-NT formation and reduced CD31 expression. In marked contrast, all these alterations were either abrogated or significantly attenuated by HS treatment. Conclusion: The therapeutic application of a transient heat stress during EVLP of damaged rat lungs reduces endothelial permeability, attenuates pulmonary vasoconstriction, prevents src-kinase activation and VE-cadherin phosphorylation, while reducing endothelial peroxinitrite generation and the release of cytokines and endothelial biomarkers. Collectively, these data demonstrate that therapeutic heat stress may represent a promising strategy to protect the lung endothelium from severe reperfusion injury. [ABSTRACT FROM AUTHOR]

Introduction: Ultrasound measurement of the radial resistance index (RRI) in the anatomical snuffbox has been proposed as a useful method for assessing the systemic vascular resistance index (SVRI). This study aims to establish the correlation between SVRI measured by pulmonary artery catheter (PAC) and RRI. Methods: A cross-sectional study included all consecutive patients undergoing postoperative (POP) cardiac surgery with hemodynamic monitoring using PAC. Hemodynamic assessment was performed using PAC, and RRI was measured with ultrasound in the anatomical snuffbox. The Pearson correlation test was used to establish the correlation between RRI and SVRI measured using PAC. Hemodynamic behavior concerning RRI with a cutoff point of 1.1 (described to estimate under SVRI) was examined. Additionally, consistency between two evaluators was assessed for RRI using the intraclass correlation coefficient and Bland-Altman analysis. Results: A total of 35 measurements were obtained. The average cardiac index (CI) was 2.73 ± 0.64 L/min/m², and the average SVRI was 1967.47 ± 478.33 dyn·s·m²/cm5. The correlation between RRI and SVRI measured using PAC was 0.37 [95% CI 0.045–0.62]. The average RRI was 0.94 ± 0.11. RRI measurements > 1.1 had a mean SVRI of 2120.79 ± 673.48 dyn·s·m²/cm5, while RRI measurements ≤ 1.1 had a mean SVRI of 1953.1 ± 468.17 dyn·s·m²/cm5 (p = 0.62). The consistency between evaluators showed an intraclass correlation coefficient of 0.88 [95% CI 0.78–0.93], and Bland-Altman analysis illustrated adequate agreement of RRI evaluators. Conclusions: For patients in cardiac surgery POP, the correlation between the SVRI measured using PAC and the RRI measured in the anatomical snuffbox is low. Using the RRI as a SVRI estimator for patients is not recommended in this clinical scenario. [ABSTRACT FROM AUTHOR]

Background: Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model. Methods: This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied. Results: Pulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs. Conclusion: In an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden. [ABSTRACT FROM AUTHOR]

Background: Stroke volume can be estimated beat-to-beat and non-invasively by pulse wave analysis (PWA). However, its reliability has been questioned during marked alterations in systemic vascular resistance (SVR). We studied the effect of SVR on the agreement between stroke volume by PWA and Doppler ultrasound during reductions in stroke volume in healthy volunteers. Methods: In a previous study we simultaneously measured stroke volume by PWA (SVPWA) and suprasternal Doppler ultrasound (SVUS). We exposed 16 healthy volunteers to lower body negative pressure (LBNP) to reduce stroke volume in combination with isometric hand grip to elevate SVR. LBNP was increased by 20 mmHg every 6 minutes from 0 to 80 mmHg, or until hemodynamic decompensation. The agreement between SVPWA and SVUS was examined using Bland-Altman analysis with mixed regression. Within-subject limits of agreement (LOA) was calculated from the residual standard deviation. SVRUS was calculated from SVUS. We allowed for a sloped bias line by introducing the mean of the methods and SVRUS as explanatory variables to examine whether the agreement was dependent on the magnitude of stroke volume and SVRUS. Results: Bias ± limits of agreement (LOA) was 27.0 ± 30.1 mL. The within-subject LOA was ±11.1 mL. The within-subject percentage error was 14.6%. The difference between methods decreased with higher means of the methods (-0.15 mL/mL, confidence interval (CI): -0.19 to -0.11, P<0.001). The difference between methods increased with higher SVRUS (0.60 mL/mmHg × min × L-1, 95% CI: 0.48 to 0.72, P<0.001). Conclusion: PWA overestimated stroke volume compared to Doppler ultrasound during reductions in stroke volume and elevated SVR in healthy volunteers. The agreement between SVPWA and SVUS decreased during increases in SVR. This is relevant in settings where a high level of reliability is required. [ABSTRACT FROM AUTHOR]

Objectives: To examine whether long-term air pollution exposure is associated with central hemodynamic and brachial artery stiffness parameters. Methods: We assessed central hemodynamic parameters including central blood pressure, cardiac parameters, systemic vascular compliance and resistance, and brachial artery stiffness measures [including brachial artery distensibility (BAD), compliance (BAC), and resistance (BAR)] using waveform analysis of the arterial pressure signals obtained from a standard cuff sphygmomanometer (DynaPulse2000A, San Diego, CA). The long-term exposures to particles with an aerodynamic diameter < 2.5 μm (PM2.5) and nitrogen dioxide (NO2) for the 3-year periods prior to enrollment were estimated at residential addresses using fine-scale intra-urban spatiotemporal models. Linear mixed models adjusted for potential confounders were used to examine associations between air pollution exposures and health outcomes. Results: The cross-sectional study included 2,387 Chicago residents (76% African Americans) enrolled in the ChicagO Multiethnic Prevention And Surveillance Study (COMPASS) during 2013–2018 with validated address information, PM2.5 or NO2, key covariates, and hemodynamics measurements. We observed long-term concentrations of PM2.5 and NO2 to be positively associated with central systolic, pulse pressure and BAR, and negatively associated with BAD, and BAC after adjusting for relevant covariates. A 1-µg/m3 increment in preceding 3-year exposures to PM2.5 was associated with 1.8 mmHg higher central systolic (95% CI: 0.98, 4.16), 1.0 mmHg higher central pulse pressure (95% CI: 0.42, 2.87), a 0.56%mmHg lower BAD (95% CI: -0.81, -0.30), and a 0.009 mL/mmHg lower BAC (95% CI: -0.01, -0.01). Conclusion: This population-based study provides evidence that long-term exposures to PM2.5 and NO2 is related to central BP and arterial stiffness parameters, especially among African Americans. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is known to be associated with cardiovascular compromise and a major risk factor for the development of hypertensive disorders in pregnancy. However, little is known about the effect of obesity on maternal cardiac function. The aim of this study was to investigate the effect of obesity on the maternal cardiovascular system. Material and methods: This was a prospective, observational, longitudinal study. Pregnant women with booking body mass index (BMI) ≥30 kg/m2 were compared with pregnant women with normal booking BMI 20–24.9 kg/m2. Participants were seen at three time points during pregnancy; 12–14, 20–24 and 30–32 weeks. At all visits, maternal blood pressure (BP) was measured, and cardiac geometry and function were assessed using two‐dimensional trans‐thoracic echocardiography. Multilevel linear mixed‐effects models were used for all the comparisons. Results: Fifty‐nine pregnant women with obesity were compared with 14 pregnant women with normal BMI. In women with obesity, the maternal BP, heart rate and cardiac output were higher and peripheral vascular resistance was lower (p < 0.01 for all comparisons) compared with normal BMI women. Women with obesity had altered cardiac geometry with higher left ventricular end diastolic diameter, intraventricular septal thickness, posterior wall diameter, relative wall thickness and left ventricular mass (p < 0.001 for all comparisons). There was also evidence of impaired diastolic indices in the obese group with a lower E/A ratio, tissue Doppler imaging E′ lateral and medial and higher left atrial volume (p < 0.01 for all comparisons). Finally, women with obesity had reduced longitudinal function, as assessed by mitral plane annular systolic excursion, between the second and third trimester of pregnancy, indicating possible early cardiac dysfunction in this group. Conclusions: Obesity is associated with maternal hyperdynamic circulation, altered cardiac geometry and suboptimal diastolic function, compared with normal BMI pregnant women, and these factors may contribute to the increased risk of complications in obese pregnant women. [ABSTRACT FROM AUTHOR]

Early in the twentieth century, Walter B. Cannon (1871–1945) introduced his overarching hypothesis of "homeostasis" (Cannon 1932)—the ability to sustain physiological values within a narrow range necessary for life during periods of stress. Physical exercise represents a stress in which motor, respiratory and cardiovascular systems must be integrated across a range of metabolic stress to match oxygen delivery to oxygen need at the cellular level, together with appropriate thermoregulatory control, blood pressure adjustments and energy provision. Of these, blood pressure regulation is a complex but controlled variable, being the function of cardiac output and vascular resistance (or conductance). Key in understanding blood pressure control during exercise is the coordinating role of the autonomic nervous system. A long history outlines the development of these concepts and how they are integrated within the exercise context. This review focuses on the renaissance observations and thinking generated in the first three decades of the twentieth century that opened the doorway to new concepts of inquiry in cardiovascular regulation during exercise. The concepts addressed here include the following: (1) exercise and blood pressure, (2) central command, (3) neurovascular transduction with emphasis on the sympathetic nerve activity and the vascular end organ response, and (4) tonic neurovascular integration. [ABSTRACT FROM AUTHOR]

Simple Summary: Pulmonary hypertension is a fatal comorbidity in dogs with left-sided heart disease. Various oral pulmonary vasodilators have been effective in treating canine pulmonary hypertension; however, no studies have compared their hemodynamic effects. This study compared the hemodynamic effects of selected pulmonary vasodilators (15 µg/kg beraprost, 1.0 mg/kg sildenafil, and their combination) in canine models of mitral regurgitation (the most common cardiac disease in dogs). Significant improvements in pulmonary hypertension were observed with all study drugs. Pulmonary vasodilating effects differed among the study's drugs. Sildenafil showed a more potent pulmonary vasodilating effect than beraprost; however, sildenafil significantly worsened the left-heart loading condition. Although beraprost showed a weaker pulmonary vasodilating effect than sildenafil, no significant worsening in the left-heart loading condition was observed. Combination therapy resulted in the strongest pulmonary and systemic vasodilating effects without worsening the left-heart loading condition. This study demonstrated the differences between beraprost and sildenafil in pulmonary and systemic vasodilating effects. Sildenafil involved the risk of worsening the left-heart load, although it was effective in treating pulmonary hypertension. Combination therapy with beraprost and sildenafil synergistically dilated the pulmonary and systemic vessels, indicating a more potent treatment option. Previous reports have shown that various oral pulmonary vasodilators are effective against canine pulmonary hypertension (PH). However, no studies have compared their hemodynamic effects. We aimed to compare the hemodynamic effects of 15 µg/kg beraprost sodium, 1.0 mg/kg sildenafil, and their combination, in dogs with experimentally induced mitral regurgitation. This experimental crossover study evaluated the hemodynamic and functional effects of oral pulmonary vasodilators by application of right-sided heart catheterization and echocardiography. Beraprost significantly decreased pulmonary and systemic vascular resistance. Additionally, beraprost increased right-ventricular stroke volume and left-ventricular cardiac output without worsening left-heart size and left-atrial pressure. The pulmonary vasodilatory effects of sildenafil were stronger, and its systemic vasodilatory effects were weaker than those of beraprost. However, sildenafil significantly increased the left-ventricular volume, left-atrial pressure indicator, and right-ventricular cardiac output. Combination therapy resulted in the strongest pulmonary and systemic vasodilating effects without worsening the left-heart size and left-atrial pressure indicators. Both beraprost and sildenafil were effective against canine PH; however, sildenafil was associated with the risk of worsening left-heart loading. Combination therapy with beraprost and sildenafil synergistically dilated pulmonary and systemic vessels, indicating a more potent treatment option for severe PH cases. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance is a major etiological factor in obesity, type 2 diabetes, and cardiovascular disease (CVD). Endothelial dysfunction may precede impairments in insulin-stimulated glucose uptake, thereby making it a key feature in development of CVD. However, the mechanism by which vascular tissue becomes dysfunctional is not clear. Summary: Extracellular vesicles (EVs) have emerged as potential mediators of insulin resistance and vascular dysfunction. EVs are membrane-bound particles released by tissues following cellular stress or activation. They carry "cargo" (e.g., insulin signaling proteins, eNOS-nitric oxide, and miRNA) that are believed to promote inter-cellular and interorgan communications. Herein, we review the underlying physiology of EVs in relation to type 2 diabetes and CVD risk. Specifically, we discuss how EVs may modulate metabolic (e.g., skeletal muscle, liver, and adipose) insulin sensitivity, and propose that EVs may modulate vascular insulin action to influence both endothelial function and arterial stiffness. We lastly identify how EVs may play a unique role following exercise to promote metabolic and vascular insulin sensitivity changes. Key Message: Gaining insight toward insulin-mediated EV mechanism has potential to identify novel pathways regulating cardiometabolic health and provide foundation for examining EVs as unique biomarkers and targets to prevent and/or treat chronic diseases. [ABSTRACT FROM AUTHOR]

The association between cerebral hemodynamics and cognitive impairment has been reported in neurodegenerative and cerebrovascular disorders (CVD). However, it is still unclear whether changes occur in the acute phase of CVD. Here we investigated cognitive and hemodynamic parameters and their association in patients with CVD during the acute and subacute phases. Seventy-three patients with mild stroke, not undergoing endovascular treatment, were recruited. All subjects were devoid of intracranial or external carotid stenosis, significant chronic cerebrovascular pathology, dementia or non-compensated cardiovascular diseases. Patients were evaluated within 7 days from symptoms onset (T1) and after 3 months (T2). Clinical and demographic data were collected. NIHSS, MoCA, FAB, and Word-Color Stroop test (WCST) were used to evaluate disease severity and cognitive functions. Basal hemodynamic parameters in the middle cerebral artery were measured with transcranial Doppler. Differences between T2 and T1, correlations between cognitive and hemodynamic variables at T1 and T2, as well as correlations between the T2-T1 variation in cognitive and hemodynamic parameters were assessed. At T1, cognitive performance of MoCA, FAB, and WCST was lower compared with T2; and pulsatility index, a parameter reflecting distal vascular resistance, was higher. However, no correlations between the changes in cognitive and hemodynamic variables were found; therefore, the two seems to be independent phenomena. In the acute phase, the linear association between cerebral blood flow and cognitive performances was lost, probably due to a differential effect of microenvironment changes and vascular-specific phenomena on cognition and cerebral hemodynamics. This relationship was partially restored in the subacute phase. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the effect of right ventricular energy failure (RVEF) on hemodynamic and clinical outcomes in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA) surgery or balloon pulmonary angioplasty (BPA). Patients and Methods: A total of 100 CTEPH patients planned for PEA or BPA were included in the study. Based on the presence of RVEF during diagnosis, patients divided into two groups. Hemodynamic data from right heart catheterization (RHC) were compared before and after procedures in 3-6 months follow up period. Results: Patients with RVEF revealed a decrease in mean pulmonary artery pressure (mPAP) from 54.67±12.27 mmHg to 36.12±11.76 mmHg (p:<0.001), mean right atrial pressure (mRAP) from 13.40±4.08 mmHg to 9.76±4.56 mmHg (p:0.003), and pulmonary vascular resistance (PVR) from 11.36±5.15 Wood Units (WU) to 5.46±3.30 WU (p <0.001). In the non-RVEF group, mPAP decreased from 38.82±12.61 mmHg to 30.81±10.57 mmHg (p:<0.001), mRAP from 7.09±3.02mmHg to 7.15±3.07mmHg (p: 0.917), and PVR from 6.33±3.65 WU to 4.09±2.31 WU (p:<0.001). Conclusion:The presence of RVEF at the time of diagnosis in CTEPH patients does not have a negative impact on early perioperative and 3-month postoperative outcomes following PEA or BPA. This high-risk patient group demonstrated significant hemodynamic and clinical benefits from both PEA and BPA. [ABSTRACT FROM AUTHOR]

We propose a mathematical model of the human cardiovascular and respiratory systems. The cardiovascular segment of the model simulates the main heart rate, oscillating blood pressure, peripheral vascular resistance, and nonlinear dynamics of the autonomic control of circulation, namely α- and β- sympathetic and parasympathetic control. The respiratory part includes central pattern generator, lungs, and a control loop sensitive to the concentration of CO2 and O2 in the arterial blood. Both parts of the model are linked in a physiological manner. The adequacy of the model is demonstrated by comparing the simulated time series to the experimental records of healthy subjects from the SIESTA database using spectral analysis, statistical analysis, and nonlinear measures of directional coupling. The proposed model can become a useful tool for investigation of the cardiovascular dynamics during sleep. [ABSTRACT FROM AUTHOR]