Pulmonary Arterial Blood Research Articles

A novel large animal model of smoke inhalation-induced acute respiratory distress syndrome

BackgroundAcute respiratory distress syndrome (ARDS) is multifactorial and can result from sepsis, trauma, or pneumonia, amongst other primary pathologies. It is one of the major causes of death in critically ill patients with a reported mortality rate up to 45%. The present study focuses on the development of a large animal model of smoke inhalation-induced ARDS in an effort to provide the scientific community with a reliable, reproducible large animal model of isolated toxic inhalation injury-induced ARDS.MethodsAnimals (n = 21) were exposed to smoke under general anesthesia for 1 to 2 h (median smoke exposure = 0.5 to 1 L of oak wood smoke) after the ultrasound-guided placement of carotid, pulmonary, and femoral artery catheters. Peripheral oxygen saturation (SpO2), vital signs, and ventilator parameters were monitored throughout the procedure. Chest x-ray, carotid, femoral and pulmonary artery blood samples were collected before, during, and after smoke exposure. Animals were euthanized and lung tissue collected for analysis 48 h after smoke inhalation.ResultsAnimals developed ARDS 48 h after smoke inhalation as reflected by a decrease in SpO2 by approximately 31%, PaO2/FiO2 ratio by approximately 208 (50%), and development of bilateral, diffuse infiltrates on chest x-ray. Study animals also demonstrated a significant increase in IL-6 level, lung tissue injury score and wet/dry ratio, as well as changes in other arterial blood gas (ABG) parameters.ConclusionsThis study reports, for the first time, a novel large animal model of isolated smoke inhalation-induced ARDS without confounding variables such as cutaneous burn injury. Use of this unique model may be of benefit in studying the pathophysiology of inhalation injury or for development of novel therapeutics.

Rehabilitation Effects of Acupuncture on the Diaphragm Dysfunction in Chronic Obstructive Pulmonary Disease: A Systematic Review.

IntroductionDiaphragm dysfunction is a significant extrapulmonary effect in chronic obstructive pulmonary disease (COPD), which is manifested by changes in diaphragm structure and reduced diaphragm strength. Acupuncture is a traditional rehabilitation technique in China, which has been used in rehabilitation for COPD. But whether acupuncture can improve the diaphragm function of COPD patients remains to be verified.ObjectiveThe objective of this study was to evaluate the rehabilitation effects of acupuncture on diaphragm dysfunction in patients with COPD.MethodsThe authors retrieved in CNKI, VIP, SinoMed, PubMed, Ebsco, Web of Science, from inception to November 2020, for relevant randomized control trials. Two researchers independently screened the articles and extracted the data. The quality of the included studies was evaluated by Physiotherapy Evidence Database scale. The primary outcome measures were maximal inspiratory pressure and the scale for accessory respiratory muscle mobilization, the secondary outcome measures were pulmonary function-related indicators and arterial blood gas indicators.ResultsNine articles were finally obtained. Seven studies added acupuncture to standard treatment for patients with diaphragm dysfunction in COPD and found statistically significant changes in the maximum inspiratory pressure and the scale for accessory respiratory muscle mobilization. Two studies have proved that use acupuncture combined with other Traditional Chinese Medicine methods in the rehabilitation for COPD can effectively improve the diaphragm strength and diaphragmatic motor performance. Seven studies showed that acupuncture has obvious improvement in pulmonary ventilation function. Seven studies reported significant differences in arterial blood gas pre- to post-intervention.ConclusionThis systematic review found that acupuncture can effectively enhance the diaphragm strength, relieve respiratory muscle fatigue, it can also play a promoting role in improving lung function, hypoxia, and carbon dioxide retention, as well as preventing and alleviating respiratory failure. The generalizability of these results is limited by the design of the included studies.

Impact of Pharmacologically Left Shifting the Oxygen-Hemoglobin Dissociation Curve on Arterial Blood Gases and Pulmonary Gas Exchange During Maximal Exercise in Hypoxia.

Stewart, Glenn M., Troy J. Cross, Michael J. Joyner, Steven C. Chase, Timothy Curry, Josh Lehrer-Graiwer, Kobina Dufu, Nicholas E. Vlahakis, and Bruce D. Johnson. Impact of pharmacologically left shifting the oxygen-hemoglobin dissociation curve on arterial blood gases and pulmonary gas exchange during maximal exercise in hypoxia. High Alt Med Biol. 22:249-262, 2021. Introduction: Physiological and pathological conditions, which reduce the loading of oxygen onto hemoglobin (Hb), can impair exercise capacity and cause debilitating symptoms. Accordingly, this study examined the impact of pharmacologically left shifting the oxygen-hemoglobin dissociation curve (ODC) on arterial oxygen saturation (SaO2) and exercise capacity. Methods: Eight healthy subjects completed a maximal incremental exercise test in hypoxia (FIO2: 0.125) and normoxia (FIO2: 0.21) before (Day 1) and after (Day 15) daily ingestion of 900 mg of voxelotor (an oxygen/Hb affinity modulator). Pulmonary gas exchange and arterial blood gases were assessed throughout exercise and at peak. Data for a 1,500 mg daily drug dose are reported in a limited cohort (n = 3). Results: Fourteen days of drug administration left shifted the ODC (p50 measured under standard conditions, Day 1: 28.0 ± 2.1 mmHg vs. Day 15: 26.1 ± 1.8 mmHg, p < 0.05). Throughout incremental exercise in hypoxia, SaO2 was systematically higher after drug (peak exercise SaO2 on Day 1: 71 ± 2 vs. Day 15: 81% ± 2%, p < 0.001), whereas oxygen extraction (Ca-vO2 diff) and consumption (VO2) were similar (peak exercise Ca-vO2 diff on Day 1: 11.5 ± 1.7 vs. Day 15: 11.0 ± 1.8 ml/100 ml blood, p = 0.417; peak VO2 on Day 1: 2.59 ± 0.39 vs. Day 15: 2.47 ± 0.43 l/min, p = 0.127). Throughout incremental exercise in normoxia, SaO2 was systematically higher after drug, whereas peak VO2 was reduced (peak exercise SaO2 on Day 1: 93.9 ± 1.8 vs. Day 15: 95.8% ± 1.0%, p = 0.008; peak VO2 on Day 1: 3.62 ± 0.55 vs. Day 15: 3.26 ± 52 l/min, p = 0.001). Conclusion: Pharmacologically increasing the affinity of Hb for oxygen improved SaO2 during hypoxia without impacting exercise capacity; however, left shifting the ODC in healthy individuals appears detrimental to exercise capacity in normoxia. Left shifting the ODC to different magnitudes and under more chronic forms of hypoxia warrants further study.

Effect of maternal oxytocin on umbilical venous and arterial blood flows during physiological-based cord clamping in preterm lambs.

BackgroundDelayed umbilical cord clamping (UCC) after birth is thought to cause placental to infant blood transfusion, but the mechanisms are unknown. It has been suggested that uterine contractions force blood out of the placenta and into the infant during delayed cord clamping. We have investigated the effect of uterine contractions, induced by maternal oxytocin administration, on umbilical artery (UA) and venous (UV) blood flows before and after ventilation onset to determine whether uterine contractions cause placental transfusion in preterm lambs.Methods and findingsAt ~128 days of gestation, UA and UV blood flows, pulmonary arterial blood flow (PBF) and carotid arterial (CA) pressures and blood flows were measured in three groups of fetal sheep during delayed UCC; maternal oxytocin following mifepristone, mifepristone alone, and saline controls. Each successive uterine contraction significantly (p<0.05) decreased UV (26.2±6.0 to 14.1±4.5 mL.min-1.kg-1) and UA (41.2±6.3 to 20.7 ± 4.0 mL.min-1.kg-1) flows and increased CA pressure and flow (47.1±3.4 to 52.8±3.5 mmHg and 29.4±2.6 to 37.3±3.4 mL.min-1.kg-1). These flows and pressures were partially restored between contractions, but did not return to pre-oxytocin administration levels. Ventilation onset during DCC increased the effects of uterine contractions on UA and UV flows, with retrograde UA flow (away from the placenta) commonly occurring during diastole.ConclusionsWe found no evidence that amplification of uterine contractions with oxytocin increase placental transfusion during DCC. Instead they decreased both UA and UV flow and caused a net loss of blood from the lamb. Uterine contractions did, however, have significant cardiovascular effects and reduced systemic and cerebral oxygenation.

Identification of the molecular mechanisms underlying brisket disease in Holstein heifers via microbiota and metabolome analyses

Brisket disease (BD) is common among Holstein heifers in high-altitude environments, and this disease may result in serious economic loss. At present, no effective treatment is available for brisket disease. In this study, liver and cecum samples were collected from five heifers with BD and five healthy heifers (HH) for analyses of the metabolome and microbiota. The mean pulmonary arterial pressure and systolic blood pressure were significantly higher in BD heifers, whereas the average breathing rate, blood oxygen saturation, and glucose level were significantly lower in BD group than in the HH group. Further, 16S rDNA data showed that the abundance of Firmicutes was significantly lower and that of Bacteroidetes was significantly higher in BD group than in the HH group. At the genus level, the BD group heifers harbored fewer Ruminococcaceae and Lachnospiraceae than the HH group. Several metabolites, including beta-d-fructose, d-ribose, 1,4-beta-d-glucan, sucrose, and glucose-6-phosphate were present at low levels in BD heifers. Moreover, the mean pulmonary arterial pressure was negatively correlated with beta-d-fructose (r = − 0.74; P = 0.013), d-ribose (r = − 0.72; P = 0.018), and acetyl-tyrosine-ethyl-ester (r = − 0.71; P = 0.022). We also found that mean pulmonary arterial pressure was negatively correlated with most of the genera, including those in the families of Lachnospiraceae and Ruminococcaceae. In summary, the decreased levels of metabolites and microbial genera might affect BD by limiting the energy supply. This study may help us better understand the role of the microbiota in BD and provide new insights into the management of feeding to decrease the rate of BD in Holstein dairy cows in the Qinghai-Tibetan plateau.

MO746CARDIAC REMODELING AND PULMONARY HYPERTENSION IN HEMODIALYSIS PATIENTS

Abstract Background and Aims An important predictor of cardiovascular mortality and morbidity in hemodialysis patients is left ventricular hypertrophy. Also, pulmonary hypertension is a risk factor for mortality and cardiovascular events in hemodialysis patients. The aim of this study was to investigate cardiac remodeling and the dynamics of pulmonary arterial pressure during a year-long hemodialysis treatment and to evaluate relationship between pulmonary arterial pressure and blood flow in arteriovenous fistula. Method Hemodialysis patients (n=88; 42 males, 46 females, mean age was 51.7±13.0 years) were studied. Echocardiography and Doppler echocardiography were performed in the beginning of hemodialysis treatment and after a year. Echocardiographic evaluation was carried out on the day after dialysis. Left ventricular mass index (LVMI) was calculated. Left ventricular ejection fraction (LVEF) was measured by the echocardiographic Simpson method. Arteriovenous fistula flow was determined by Doppler echocardiography. Pulmonary hypertension was diagnosed according to criteria of Guidelines for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology. Results Pulmonary hypertension was diagnosed in 47 (53.4%) patients. Left ventricular hypertrophy was revealed in 71 (80.7%) patients. Only 2 (2.3%) patients had LVEF&amp;lt;50%. At the beginning of hemodialysis correlation was detected between systolic pulmonary arterial pressure and LVMI (r=0.52; P&amp;lt;0.001). Systolic pulmonary arterial pressure negatively correlated with left ventricular ejection fraction (r=-0.20; P=0.04). After a year of hemodialysis treatment LVMI decreased from 140.49±42.95 to 123.25±39.27 g/m2 (р=0.006) mainly due to a decrease in left ventricular end-diastolic dimension (from 50.23±6.48 to 45.13±5.24 mm, p=0.04) and systolic pulmonary arterial pressure decreased from 44.83±14.53 to 39.14±10.29 mmHg (р=0.002). Correlation wasn’t found between systolic pulmonary arterial pressure and arteriovenous fistula flow (r=0.17; p=0.4). Conclusion Pulmonary hypertension was diagnosed in half of patients at the beginning of hemodialysis treatment. Pulmonary hypertension in hemodialysis patients was associated with left ventricular hypertrophy, systolic left ventricular dysfunction. After a year-long hemodialysis treatment, a regress in left ventricular hypertrophy and a partial decrease in pulmonary arterial pressure were observed. There wasn’t correlation between arteriovenous fistula flow and systolic pulmonary arterial pressure.

A Probabilistic Approach for Contact Stability and Contact Safety Analysis of Robotic Intracardiac Catheter.

The disturbances caused by the blood flow and tissue surface motions are major concerns during the motion planning of an intracardiac robotic catheter. Maintaining a stable and safe contact on the desired ablation point is essential for achieving effective lesions during the ablation procedure. In this paper, a probabilistic formulation of the contact stability and the contact safety for intravascular cardiac catheters under the blood flow and surface motion disturbances is presented. Probabilistic contact stability and contact safety metrics, employing a sample-based representation of the blood flow velocity distribution and the heart motion trajectory, are introduced. Finally, the contact stability and safety for an magnetic resonance imaging-actuated robotic catheter under main pulmonary artery blood flow disturbances and left ventricle surface motion disturbances are analyzed in simulation as example scenarios.

Right ventricular expression of NT-proBNP adds predictive value to REVEAL score in patients with pulmonary arterial hypertension.

AimsThe Registry to Evaluate Early and Long‐Term PAH Disease Management (REVEAL) risk scores differentiate survivals in patients with pulmonary arterial hypertension (PAH). However, measurements of N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) in the peripheral blood may not adequately reflect early‐stage decompensated heart failure (HF). Given that right heart catheterization (RHC) can facilitate measurements of intracardiac NT‐proBNP, in this study our aim was to evaluate the predictive role of right ventricular (RV) NT‐proBNP measurements in patients with PAH.Methods and resultsWe prospectively collected intracardiac blood samples for NT‐proBNP measurements from patients diagnosed with World Health Organization Group I PAH during RHC. Clinical information including the aetiology of PAH (idiopathic, connective tissue disease, or congenital heart disease) and REVEAL scores were recorded. The primary endpoint was hospitalization for decompensated HF; median duration of follow‐up was 28 months. Among the 62 patients evaluated, 12 reached the designated endpoint. REVEAL risk scores were higher among patients hospitalized for HF. We detected no significant differences in plasma NT‐proBNP levels in peripheral circulation, in the right atrium, or in pulmonary arterial blood; however, significantly higher levels of NT‐proBNP were detected in the RV in patients diagnosed with PAH. RV NT‐proBNP was a sensitive predictor (cut‐off value 1500 pg/mL) of subsequent hospitalization for HF. Our findings indicate that RV NT‐proBNP levels add predictive value to REVEAL scores with respect to future hospitalization due to HF.ConclusionsRight ventricular NT‐proBNP levels combined with REVEAL 2.0 could predict the development of subsequent HF in patients with PAH and may be a potential biomarker.

Greater reductions in blood flow after anti-angiogenic treatment in non-small cell lung cancer patients are associated with shorter progression-free survival

To evaluate tumor blood flow using 15O-water positron emission tomography (PET) in patients with non-small cell lung cancer (NSCLC) before and after chemotherapy with bevacizumab, and to investigate the effects of bevacizumab on tumor blood flow changes and progression-free survival (PFS). Twelve patients with NSCLC were enrolled. Six patients underwent chemotherapy with bevacizumab and the other six without bevacizumab. 15O-water dynamic PET scans were performed within 1 week before the start of chemotherapy and within 1 week after the first day of chemotherapy. Tumor blood flow was analyzed quantitatively using a single one-tissue compartment model with the correction of pulmonary circulation blood volume and arterial blood volume via an image-derived input function. In the bevacizumab group, mean tumor blood flow was statistically significantly reduced post-chemotherapy (pre-chemotherapy 0.27 ± 0.14 mL/cm3/min, post-chemotherapy 0.18 ± 0.12 mL/cm3/min). In the no bevacizumab group, there was no significant difference between mean tumor perfusion pre-chemotherapy (0.42 ± 0.42 mL/cm3/min) and post-chemotherapy (0.40 ± 0.27 mL/cm3/min). In the bevacizumab group, there was a positive correlation between the blood flow ratio (tumor blood flow post-chemotherapy/tumor blood flow pre-chemotherapy) and PFS (correlation coefficient 0.94). Mean tumor blood flow decreases after bevacizumab administration and was positively correlated with longer PFS.

Phase 2 Clinical Study to Evaluate the Efficacy and Safety of Inhaled GB002 for the Treatment of World Health Organization Group 1 Pulmonary Arterial Hypertension

Purpose Despite currently available therapy, the morbidity and mortality of pulmonary arterial hypertension (PAH) remains high. PAH is characterized by abnormal proliferation of pulmonary arterial smooth muscle cells, endothelial cells, and myofibroblasts. GB002 is a unique, highly potent, small molecule that targets PDGFRα/β, CSF1R, and c-KIT and modulates BMPR2, kinases implicated in the development of PAH. GB002 is formulated for inhalation delivery to directly target the diseased lung to limit systemic exposure and thereby potentially improve efficacy and tolerability. A Phase 2 study has been initiated to evaluate the efficacy and safety of inhaled GB002 in adult subjects with World Health Organization (WHO) Group 1 PAH. (NCT04456998). Methods This is a randomized, double-blind, placebo-controlled study. Patients with Functional Class II/III PAH on therapy and with a pulmonary vascular resistance (PVR) greater than or equal to 400 dyne•s/cm5 will be eligible. The planned treatment period is 24 weeks, with a target enrollment of 80 patients. Endpoints The primary endpoint is change in PVR measured by right heart catheterization from baseline to 24 weeks. The key secondary endpoint is change (baseline to 24 weeks) in 6-minute walk test (6MWT). Exploratory endpoints include quality of life, change in risk score, time to clinical worsening, and the following echocardiographic parameters: tricuspid annular systolic velocity, right ventricular (RV) Tei index and right ventricular free wall strain (RVFWS). Sub-studies include 6MWT heart rate expenditure change from baseline to 24 weeks, and changes in pulmonary arterial blood volume measured by CT imaging (baseline to 24 weeks). An Independent Data Monitoring Committee (IDMC) will ensure that benefits and risks remain acceptable during the conduct of the study. In this phase 2 study, the effects of GB002 on hemodynamics, 6MWT and other endpoints at 24 weeks will be assessed. Exploratory biomarkers will be evaluated for target engagement and response to treatment.

Tea polyphenols and Levofloxacin alleviate the lung injury of hepatopulmonary syndrome in common bile duct ligation rats through Endotoxin -TNF signaling

Background & AimsHepatopulmonary syndrome (HPS) is characterized by pulmonary vasodilation and arterial blood oxygen desaturation in patients with chronic liver disease. Generally, common bile duct ligation (CBDL) rats are a suitable experimental model for studying hepatopulmonary syndrome. Our previous study demonstrated that endotoxin surges markedly, followed by bacterial translocation and the loss of liver immune function in all the stages of CBDL, thereby contributing to the pathogenesis of HPS. However, the mechanisms behind the increase of the endotoxin and how to alleviate it have not yet been elucidated. Pulmonary injury induced by increased bilirubin, endotoxin, and inflammatory mediators occurs in the early and later stages of CBDL. This study assessed the effects of Tea polyphenols (TP) and Levofloxacin on endotoxin reduction and suppression of lung injury in HPS rats in the long and short term, respectively. MethodsMorphological change of pulmonary injury, HPS relative index, endotoxin concentration, and the activation extent of Malondialdehyde (MDA) and Myeloperoxidase (MPO) were evaluated in CBDL rats with or without TP and Levofloxacin for three weeks or six weeks. The inflammation factors of serum, lung tissue, and BALF were then compared at the same condition for the two time periods. This was followed by adoption of the network pharmacology approach, which was mainly composed of active component gathering, target prediction, HPS gene collection, network analysis, and gene enrichment analysis. Finally, the mRNA and protein levels of the inflammatory factors were studied and relative signaling expression was assessed using RT-PCR and Western blot analysis. ResultsThe obtained results indicated that the pulmonary injury manifestation was perceived and endotoxin, MDA, and MPO activation were markedly increased in the early and later stages of CBDL. TP and Levofloxacin treatment alleviated endotoxin infection and inflammation factor expression three weeks and six weeks after CBDL. In addition, Levofloxacin displayed a short time anti-bacterial effect, while TP exerted a long period function. TP and Levofloxacin also reduced TNF-α, TGF-β, IL-1β, PDGF-BB, NO, ICAM-1, and ET-1 expression on the mRNA or protein expression. With regard to the pharmacological mechanism, the network analysis indicated that 12 targets might be the therapeutic targets of TP and Levofloxacin on HPS, namely ET-1, NOs3, VEGFa, CCl2, TNF, Ptgs2, Hmox1, Alb, Ace, Cav1, and Mmp9. The gene enrichment analysis implied that TP and Levofloxacin probably benefited patients with HPS by modulating pathways associated with the AGE-RAGE signaling pathway, the TNF signaling pathway, the HIF-1 signaling pathway, the VEGF signaling pathway, and the IL-17 signaling pathway, Rheumatoid arthritis, Fluid shear stress, and atherosclerosis. Finally, the TNF-α level was mainly diminished on the protein level following CBDL. ConclusionsTP and Levofloxacin could alleviate pulmonary injury for short and long period, respectively, while at the same time preventing endotoxin and the development of HPS in CBDL rats. These effects are possibly associated with the regulation of the Endotoxin -TNF-α pathways.

Pulmonary Embolism in a Critically Ill Infant with Univentricular Parallel Circulation

AbstractA 3-month-old infant patient with hypoplastic left heart syndrome diagnosed in the prenatal period required long-term intensive care for refractory chylothorax and chylous ascites after undergoing bilateral pulmonary artery banding at age 6 days. Weaning from mechanical ventilation was difficult due to massive edema, and a central venous catheter was required because enteral feeding was hampered by the refractory chyle leakage, for which surgery was ineffective. On the evening after central venous catheter replacement was performed, his respiratory condition suddenly deteriorated; cardiac ultrasound revealed that the left pulmonary arterial blood flow had decreased, and enhanced computed tomography demonstrated a left pulmonary embolism (PE), which was identified as the cause of a sudden decrease in the pulmonary blood flow. The patient died due to refractory septic shock at age 5 months. PEs in children, especially patients with cyanotic congenital heart disease, are difficult to diagnose because of their atypical presentation. Current diagnostic criteria are based on adult guidelines, and a few factors in the criteria, such as tachycardia and hypoxia, are difficult to apply for pediatric cyanotic patients with intracardiac or extracardiac right-to-left shunt. In fact, those criteria have lower specificities in children. In conclusion, the present case suggested that a sudden decrease in the pulmonary blood flow can aid the physicians in diagnosing PE in patients with cyanotic congenital heart disease. We need more pediatric cases and evidence of PE in children to make a PE guideline, which is specific to pediatric patients including cyanotic congenital heart disease.

Galectin-3 Promotes ROS, Inflammation, and Vascular Fibrosis in Pulmonary Arterial Hypertension.

Pulmonary Arterial Hypertension (PAH) is a progressive vascular disease arising from the narrowing of pulmonary arteries (PA) resulting in high pulmonary arterial blood pressure and ultimately right ventricular (RV) failure. A defining characteristic of PAH is the excessive remodeling of PA that includes increased proliferation, inflammation, and fibrosis. There is no cure for PAH nor interventions that effectively impede or reverse PA remodeling, and research over the past several decades has sought to identify novel molecular mechanisms of therapeutic benefit. Galectin-3 (Gal-3; Mac-2) is a carbohydrate-binding lectin that is remarkable for its chimeric structure, comprised of an N-terminal oligomerization domain and a C-terminal carbohydrate-recognition domain. Gal-3 is a regulator of changes in cell behavior that contribute to aberrant PA remodeling including cell proliferation, inflammation, and fibrosis, but its role in PAH is poorly understood. Herein, we summarize the recent literature on the role of Gal-3 in the development of PAH and provide experimental evidence supporting the ability of Gal-3 to influence reactive oxygen species (ROS) production, NOX enzyme expression, inflammation, and fibrosis, which contributes to PA remodeling. Finally, we address the clinical significance of Gal-3 as a target in the development of therapeutic agents as a treatment for PAH.

Pulmonary Artery Pressure and Variations in Arterial Blood Pressure During the Induction Period of General Anesthesia in Elderly Patients.

To determine the correlation of old age, pulmonary artery pressure (PAP) and mean arterial blood pressure (MABP) during anesthetic induction in elderly patients. Prospective cohort study. Central Hospital affiliated to Chongqing Medical University from September 2016 to September 2019. A total of 75 elderly patients with pulmonary hypertension, who underwent surgery under general anesthesia, were inducted. Each 25 patients were allocated into 65-74 years, 75-84 years, and ≥85 years groups. PAP was invasively measured using a right heart floating catheter before induction, while MAP was measured using an invasive radial artery catheter at one minute before and within five minutes after anesthetic induction. PAP and PAMP, both increased with age (p <0.001). MAP at one minute before induction significantly increased with aging, while MAP measured at 1, 3 and 5 minutes after anesthetic induction, exhibited tendencies of significant decrease with aging (p <0.05). The correlation analysis results revealed that mean MAP during anesthesia induction was significantly associated with PASP before induction (r = -0.384 and -0.532 for Kendall and Spearman correlation analyses; both p<0.05). Increased PAP may be involved in the association between with aging and increased risk of hypotension during induction. Key Words: General anesthesia, Hypotension, Pulmonary arterial blood pressure, Old age.

Targeting JP2: A New Treatment for Pulmonary Hypertension.

Pulmonary hypertension (PH) is a disease with a complex etiology and high mortality rate. Abnormal pulmonary vasoconstriction and pulmonary vascular remodeling lead to an increase in mean pulmonary arterial blood pressure for which, and there is currently no cure. Junctophilin-2 (JP2) is beneficial for the assembly of junctional membrane complexes, the structural basis for excitation-contraction coupling that tethers the plasma membrane to the sarcoplasmic reticulum/endoplasmic reticulum and is involved in maintaining intracellular calcium concentration homeostasis and normal muscle contraction function. Recent studies have shown that JP2 maintains normal contraction and relaxation of vascular smooth muscle. In some experimental studies of drug treatments for PH, JP2 expression was increased, which improved pulmonary vascular remodeling and right ventricular function. Based on JP2 research to date, this paper summarizes the current understanding of JP2 protein structure, function, and related heart diseases and mechanisms and analyzes the feasibility and possible therapeutic strategies for targeting JP2 in PH.

Tumor-Infiltrating T Cells Concurrently Overexpress CD200R with Immune Checkpoints PD-1, CTLA-4, and TIM-3 in Non-Small-Cell Lung Cancer

Introduction: CD200R has been reported to be the receptor for the immune checkpoint molecule CD200 and can transduce immune-suppressive signals. In this study, we mainly focused on the expression level of CD200R in T cells in pulmonary artery (PA) blood and non-small-cell lung cancer (NSCLC) tumor tissue. Methods: Immune cells were isolated from dissected tumor samples and PA blood of NSCLC patients and analyzed with multiparameter flow cytometry. The co-expression of CD200R with other immune checkpoints, including programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), was also investigated. Results: CD200R expression was observed on the surface of approximately 75% of T cells among tumor-infiltrating leukocytes (TILs). Compared to T cells extracted from TILs, only 55% of T cells extracted from PA blood exhibited CD200R expression. Moreover, with higher expression of CD200R, the expression of other immune checkpoints, including PD-1, CTLA-4, and TIM-3, was also increased in tumor-infiltrating T cells compared to T cells in PA blood. Conclusions: Our results showed that those tumors were dominated by T cells expressing CD200R together with other checkpoints, which suggests a phenotypic change after T cell infiltration into the tumor, such as T cell exhaustion.

Higher Incidence of Atrial Fibrillation in Left Ventricular-to-Right Atrial Shunt Patients.

Background: The possible association between atrial fibrillation (AF) and left ventricular-to-right atrial shunt (LVRAS) has never been reported yet. The present study investigated the incidence of AF in LVRAS.Methods: This was a retrospective study of consecutive patients undergoing echocardiography at a single tertiary center. Clinical data, laboratory results and echocardiography parameters such as right atrial area (RAA), right ventricular end diastolic diameter (RVDD) and left atrial diameter (LAD) were compared between LVRAS group and non-LVRAS patients, and between AF and non-AF patients. Propensity score matching was performed to decrease the effect of confounders. Logistic regression analysis and mediation analysis were used to estimate the relationship between LVRAS and AF.Results: A total of 3,436 patients were included, and the incidence of LVRAS was 1.16% (n = 40). The LVRAS group had significantly larger RAA, RVDD and LAD compared with non-LVRAS group. Those who suffered from AF showed larger RAA, RVDD and LAD compared with those who maintained sinus rhythm. Multivariable logistic regression showed that gender (OR: 0.608), age (OR: 1.048), LAD (OR: 1.111), mean pulmonary artery blood pressure (mPAP, OR: 1.023), TR (OR: 2.309) and LVRAS (OR: 12.217) were significant factors for AF. RAA could partially mediate the relationship between LVRAS and AF according to the result of mediation analysis.Conclusions: Our study suggested that LVRAS, TR, LAD, mPAP, age and male were risk factors for AF. RA enlargement might underlie mechanism in the higher incidence of AF in LVRAS patients. These findings should be confirmed in larger prospective studies.

Clinical manifestation, laboratory findings, and outcome of children with cystic fibrosis over a 10-year period in South Iran

BackgroundCystic fibrosis (CF) is a monogenic hereditary disease with diverse complications, which substantially reduce the quality of life and longevity of patients. With regard to the scarcity of information on epidemiological aspects of this disease in Iran, we aimed to examine the current status of pediatric CF patients in a tertiary referral center in south Iran.ResultsMedical records of 105 patients (51% female) with the mean age of 16.3 ± 34.4 months were reviewed. Twelve patients (13.3%) had siblings with CF. Failure to thrive and respiratory symptoms were the most common presentations. Elevated liver enzymes and steatorrhea were detected in over half of tested patients, while abnormal serum albumin level, urinalysis, positive urine cultures, and positive acute phase reactants were noticed in less than half of the patients. Mild increase in pulmonary artery blood pressure was the most common finding of echocardiography. Increased liver echogenicity was the top finding of abdominopelvic sonography. Out of 42 available patients, 19 (45.2%) died with the mean age of 54.4 ± 101.8 months. The highest rate of mortality was observed in the 2–6 years old age group (42.9%).ConclusionIncreased liver echogenicity was the most common finding in hepatobiliary evaluation. Mild increase in pulmonary artery blood pressure was the most common finding of echocardiography.

Cardiac magnetic resonance using fused 3D cine and 4D flow sequences:Validation of ventricular and blood flow measurements

PurposeCurrent cardiovascular magnetic resonance (CMR) examinations require expert planning, multiple breath holds, and 2D imaging. To address this, we sought to develop and validate a comprehensive free-breathing 3D cine function and flow CMR examination using a steady-state free precession (SSFP) sequence to depict anatomy fused with a spatially registered phase contrast (PC) sequence for blood flow analysis. MethodsIn a prospective study, 25 patients underwent a CMR examination which included a 3D cine SSFP sequence and a 3D cine PC (also known as 4D flow) sequence acquired during free-breathing and after the administration of a gadolinium-based contrast agent. Both 3D sequences covered the heart and mediastinum, and used retrospective vectorcardiogram gating (20 phases/beat interpolated to 30 phases/beat) and prospective respiratory motion compensation confining data acquisition to end-expiration. Cardiovascular measurements derived from the 3D cine SSFP and PC images were then compared with those from standard 2D imaging. ResultsAll 3D cine SSFP and PC acquisitions were completed successfully. The mean time for the 3D cine sequences including prescription was shorter than that for the corresponding 2D sequences (21 min vs. 36 min, P-value <0.001). Left and right ventricular end-diastolic volumes and stroke volumes by 3D cine SSFP were slightly smaller than those from 2D cine SSFP (all biases ≤5%). The blood flow measurements from the 3D and 2D sequences had close agreement in the ascending aorta (bias −2.6%) but main pulmonary artery flow was lower with the 3D cine sequence (bias −11.2%). ConclusionCompared to the conventional 2D cine approach, a comprehensive 3D cine function and flow examination was faster and yielded slightly lower left and right end-diastolic volumes, stroke volumes, and main pulmonary artery blood flow. This free-breathing 3D cine approach allows flexible post-examination data analysis and has the potential to make examinations more comfortable for patients and easier to perform for the operator.

Growth differentiation factor-15 levels in the blood around the pulmonary artery is associated with hospitalization for heart failure in patients with pulmonary arterial hypertension.

Despite no significant differences of growth differentiation factor-15 expressions in peripheral, right atrial, and right ventricular blood, in the pulmonary arterial blood, there was a significantly high level of growth differentiation factor-15 in Group I pulmonary arterial hypertension patients subsequently developing heart failure. During right heart catheterization, collecting pulmonary blood samples is suggested to measure growth differentiation factor-15.