Pulmonary Circulation Research Articles

Effects of patent foramen ovale in migraine: a metabolomics-based study.

Patent foramen ovale (PFO), a cardiac anatomical anomaly inducing abnormal haemodynamics, leads to a paradoxical bypass of the pulmonary circulation. PFO closure might alleviate migraines; however, clinical evidence and basic experiments for the relationship are lacking. To explore the effect of PFO on migraine, 371 migraineurs finishing blood tests and contrast transthoracic echocardiography for the detection of PFO were prospectively included. Multivariate regression analysis revealed that PFO was independently associated with aura, and lower cystatin-C (cys-C) and calcium levels. Among them, patients with PFO who underwent percutaneous PFO closure were continuously followed up 1year after the operation. The intensity of migraine was significantly relieved and the levels of cys-C and calcium increased after PFO closure. Untargeted and targeted metabolomics of plasma from migraineurs before and after PFO closure revealed that 5-HT and glutathione (GSH) metabolites were differentially expressed after PFO closure. The differential metabolites were then validated in the plasma and brain tissues of PFO mouse models by LC-MS/MS analysis. Desorption electrospray ionization mass imaging demonstrated that these metabolic alterations occurred mainly in the posterior cerebral cortex. Collectively, aura, cys-C and calcium could be biomarkers of migraineurs with PFO. PFO might have an impact on the posterior head associated with the regulation of 5-HT and GSH. PFO closure might relieve migraine by improving 5-HT clearance metabolism and ameliorating redox reactions. Our results may provide evidence for an indication of PFO closure in migraine and support the related potential mechanism. KEY POINTS: Aura, and levels of cystatin-C and calcium are biomarkers of migraineurs with a patent foramen ovale (PFO). The clearance of pulmonary metabolism of 5-HT and deoxygenated blood might be the reason for the improvement of migraine symptoms in patients with PFO. The posterior region of the brain is the main area responsible for PFO-induced migraine.

The superiority of veno-arterial over veno-venous extracorporeal membrane oxygenation for operative support of lung transplantation

BackgroundVeno-arterial (V-A) and veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) are crucial support modalities during lung transplantation, yet their comparative effectiveness remains unclear.MethodsWe conducted an 8-year retrospective analysis of 62 lung transplant recipients who received intraoperative ECMO (29 V-A, 33 V-V). Baseline characteristics, surgical parameters, and clinical outcomes were compared. To address potential selection bias, we employed entropy weighted inverse probability of treatment weighting (IPTW-EW).ResultsAfter IPTW-EW adjustment, V-A ECMO was associated with superior hemodynamic and respiratory parameters, including lower systolic pulmonary artery pressure (30 vs. 37 mmHg, p = 0.007), higher arterial oxygen partial pressure (119 vs. 78 mmHg, p = 0.002), and less severe pulmonary edema (Grade 1: 50% vs. 3%, Grade 2: 45% vs. 38%, Grade 3: 5% vs. 59%, p < 0.001). Notably, V-A ECMO demonstrated significantly lower 28-day (5% vs. 29%, p = 0.017) and hospital mortalities (21% vs. 69%, p = 0.035).ConclusionsV-A ECMO provides superior pulmonary circulation unloading and is associated with improved survival outcomes compared to V-V ECMO in lung transplantation, suggesting its preferential use when clinically appropriate.

Sotatercept in pulmonary hypertension and beyond.

Sotatercept binds free activins by mimicking the extracellular domain of the activin receptor type IIA (ACTRIIA). Additional ligands are BMP/TGF-beta, GDF8, GDF11 and BMP10. The binding with activins leads to the inhibition of the signalling pathway and the deactivation of the bone morphogenic protein (BMP) receptor type 2. In this way, sotatercept activates an antiproliferative signalling to the cells of the pulmonary arteries and arterioles with the aim of rebalancing the proliferative and antiproliferative pathway that characterizes the pulmonary arterial hypertension (PAH). Sotatercept is indicated for the treatment of group 1 PAH in combination with drugs that act through the endothelin receptor, nitric oxide or prostacyclin. Its effects, demonstrated in the STELLAR study, are the improvement of exercise capacity and the FC-WHO functional class, together with the reduction of the risk of clinical worsening events. In addition to its antiremodeling effects on the pulmonary circulation, sotatercept has several haematological effects that could suggest its use in the treatment of some blood disorders other than PAH. In this review, we will discuss the effects of the drug on PAH and in parallel provide an in-depth overview of its application in haematological disorders, focusing on clinical and preclinical studies.

CDK14 regulates the development and repair of lung

Cyclin-dependent kinases (CDK) 14 regulates cell cycle, tumor expansion by influencing the downstream targets of the canonical Wnt signaling pathway. However, the function of CDK14 during organ development and regeneration has not been investigated in genetically-modified animals. Here, we found that genetic ablation of Cdk14 influenced pulmonary vascular endothelial cells and alveolar epithelial cells during mice embryonic development as well as repair of lung after bleomycin or lipopolysaccharide induced injury. Genetic knockout of Cdk14 and the CDK14 covalent inhibitor FMF-04-159-2 resulted in reduction of pulmonary vessel covered area and epithelial cell number, exhibiting increased mortality and more severe lung damage after injury. Mechanistically, Cdk14 ablation inhibited the proliferation of epithelial and vascular endothelial cells, inducing cell cycle arrest at the G2/M phase. Through RNA-seq analysis of both endothelial and epithelial cells, we found that knockdown of Cdk14 controls the expression of signal transducers and activator of transcription 1 (STAT1) as well as associated genes in interferon signaling. Disruption of Cdk14 interferes with IFN-γ induced lung repair in vivo, suggesting potential crosstalk of CDK14 signaling and IFN-γ pathway. Our work highlights the importance of Cdk14 in lung development and regenerative repair through an uncharacterized CDK14- IFN-γ signaling axis.

Investigation of the sclerosing effect of increasing doses of polidocanol on pulmonary vessels: Experimental study.

Percutaneous sclerotherapy as endovascular treatment may cause severe complications beside the target area. Pulmonary embolism and thrombosis may occur. In this regard, our study aimed to reveal whether increasing systemic doses of polidocanol affects the coronary or pulmonary alveolar levels. Twenty-one Albino New Zealand rabbits, 7 rabbits per group, were used. The first group served as a control and received a 0.5 mL injection of saline; the second group received a single injection of 0.5 mL 1% polidocanol; and the third group received a single injection of 0.5 mL 2% polidocanol via the femoral vein. After anesthesia-induced decapitation on day 3, the experimental rabbits' lungs were removed in their entirety and sent to pathology for analysis. Micron-thick slices. In all lung specimens of the first 2 groups, no narrowing or obstruction was detected in the pulmonary vessels in macroscopic and microscopic evaluation. No emphysematous changes or congestion were observed. In the third group's animal lungs, congestion in pulmonary vessels, emphysematous changes, and intra-alveolar hemorrhage were found. In our study, a single injection of 0.5 mL 2% polidocanol via the femoral vein. Animal lungs, congestion in pulmonary vessels, emphysematous changes, and intra-alveolar hemorrhage were found. As a result, our study demonstrated pulmonary vascular damage with increasing doses of polidocanol. So, the dose of polidocanol should be used in a limited manner.

Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology

Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion. Re-analysis of scRNA-seq data from peripheral blood mononuclear cells from COVID-19 cases revealed increased expression levels of CD44 and SELL in neutrophils in severe COVID-19 cases compared to a healthy group, consistent with our observations in the mouse model. These findings suggest that pulmonary perfusion defects caused by neutrophil adhesion to pulmonary vessels contribute to COVID-19 severity.

Successful Anesthetic Management for Redo Mitral Valve Replacement in the Setting of Severe Postoperative Right Ventricular Failure: A Case Report

: Mitral regurgitation, a prevalent form of heart valve dysfunction, presents a significant challenge in global cardiovascular health. With diverse etiologies, this condition increasingly affects adult populations. Over the past decades, the demand for redo valvular surgeries has steadily risen. The complexity of such procedures is further compounded when patients have underlying conditions such as severe ventricular failure, chronic hypertension, anemia, or drug allergies. Right ventricular failure occurs when the right ventricle cannot maintain adequate blood flow through the pulmonary circulation to ensure proper filling of the left ventricle. This report highlights a remarkable case of mitral valve replacement (MVR) in a 46-year-old female with an extensive surgical history, including previous mitral valve repair and atrioventricular septal defect (AVSD) repair. The patient also had chronic hypertension, anemia, and a documented allergy to valsartan. During surgery, she experienced acute right ventricular failure, necessitating complex medical management. This case underscores the critical need for thorough preoperative evaluation and meticulous intraoperative medical management in patients with intricate medical histories.

LPS-induced TMBIM6 splicing drives endothelial necroptosis and aggravates ALI.

The mechanism underlying necroptosis in pulmonary vessel endothelial cells (PVECs) resulting from long non-coding RNA (lncRNA)-induced alternative splicing (AS) of target genes in acute lung injury (ALI) remains unclear. Lipopolysaccharide (LPS)-induced expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and lncRNAs was analyzed via RT-PCR in PVECs. Full-transcriptome sequencing was used to detect AS-related mRNAs. The interaction between lncRNA MALAT1 and target gene transmembrane BAX inhibitor motif-containing 6 (TMBIM6) was verified using a dual-luciferase reporter system. Necroptosis was measured as protein levels of phosphorylated receptor-interacting serine/threonine kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like (MLKL) proteins, as well as flow cytometer measurement. Antisense of MALAT1, TMBIM6, TMBIM6-225 and RIPK1 inhibitor were transfected into a rat model of LPS-induced ALI. Hematoxylin and eosin (H&E) and immunohistochemical staining were performed to evaluate lung injury. LPS upregulated the expression of TNF-α, IL-1β, IL-6, p-RIPK1, p-RIPK3, p-MLKL, MALAT1, and TMBIM6-225 (an AS isoform of MALAT1-targeted gene TMBIM6) in PVECs. However, it downregulated the expression of TMBIM6. An antisense of MALAT1 inhibited TMBIM6-225 and downregulated p-MLKL. The pro-necroptotic effect of MALAT1 was verified in an LPS-induced MALAT1/shMALAT1-transfected ALI rat model in vivo. The necroptotic effect was reversed by treatment with necrostatin-1. LPS-induced MALAT1 causes AS of TMBIM6, and the AS variant TMBIM6-225 aggravates ALI by promoting PVEC necroptosis via the p-RIPK1, p-RIPK3, and p-MLKL complex.

Is Lung Disease a Risk Factor for Sudden Cardiac Death? A Comparative Case-Control Histopathological Study.

Sudden cardiac death (SCD) constitutes approximately 50% of cardiovascular mortality. Numerous studies have established an interrelation and a strong association between SCD and pulmonary diseases, such as chronic obstructive pulmonary disease (COPD). The aim of this study is to examine the presence of more pronounced cardiopulmonary histopathological changes in individuals who died from SCD compared to the histopathological changes in those who died from violent deaths, in two groups with comparable demographic characteristics, age and sex. This retrospective case-control study investigated the histopathological changes in cardiac and pulmonary tissues in two cohorts, each comprising 40 cases of SCD and 40 cases of violent death (self-inflicted hanging). Forensic autopsies were conducted at the Maramureș County Forensic Medicine Service, Romania, between 2019 and 2020. The mean ages recorded were 43.88 years (SD 5.49) for the SCD cohort and 41.98 years (SD 8.55) for the control cohort. In the SCD cases, pulmonary parenchyma exhibited inflammatory infiltrate in 57.5% (23), fibrosis in 62.5% (25), blood extravasation in 45% (18), and vascular media thickening in 37.5% (15), compared to the control cohort, where these parameters were extremely low. In myocardial tissue, fibrosis was identified in 47.5% (19) and subendocardial adipose tissue in 22.5% (9) of the control cohort. A close association exists between SCD and the histopathological alterations observed in the pulmonary parenchyma, including inflammation, fibrosis, emphysema, blood extravasation, stasis, intimal lesions, and vascular media thickening in intraparenchymal vessels. Both the histopathological modifications in the pulmonary parenchyma and vessels, as well as those in myocardial tissue, were associated with an increased risk of SCD, ranging from 2.17 times (presence of intimal lesions) to 58.50 times (presence of interstitial and perivascular inflammatory infiltrate in myocardial tissue).

Application-based remote interstage home monitoring for infants with shunt- or duct-dependent pulmonary perfusion.

Interstage home monitoring (IHM) programs are considered standard of care after Norwood palliation and have led to substantial improvements in clinical outcomes. This study aims to evaluate an application-based remote IHM program for infants with shunt- or duct-dependent pulmonary circulation. The primary goals were to discharge infants from the hospital while minimizing mortality, optimizing somatic growth, and enhancing caregivers' confidence in the clinical management at home. Infants with shunt-dependent single ventricle physiology or complex biventricular physiology requiring staged palliation with aortopulmonary shunt were enrolled for the study. Caregivers completed a comprehensive education program on the clinical management of their child at home and were asked to remotely send monitoring data using an application. We analyzed demographic data and clinical outcomes; evaluated patient acceptance and adherence, as well as data entry patterns and metrics; and compared these to a historical control group monitored in a non-remote IHM program and with a propensity score-matched cohort adjusted for baseline characteristics. We enrolled 30 infants in the remote IHM program between July 2021 and May 2024. The median duration of IHM was 110 days (IQR 75-140). A median of 353 (IQR 351-743) data entries were sent per patient during IHM of which 0.8% (IQR 0.3-1.9) were pathological. Readmissions (63%) and interventions (57%) were common, mainly due to cyanosis and infections. As all infants survived stage II palliation, interstage mortality could be reduced to 0% compared to 10.3% in the historical control group and was significantly lower compared to the propensity score-matched cohort with 14% (P = 0.032). Application-based remote IHM for infants with duct- or shunt-dependent pulmonary perfusion is feasible, with high acceptance and adherence. The program significantly reduced interstage mortality compared to traditional monitoring methods. Remote patient monitoring (RPM) improves communication between caregivers and healthcare teams, allowing for early intervention and optimized patient outcomes. RPM has the potential to improve outcomes, enhance patient safety, and reduce family burden in this high-risk population.

Multiscale Three-Dimensional Evaluation and Analysis of Murine Lung Vasculature From Macro- to Micro-Structural Level.

The pulmonary vasculature plays a pivotal role in the development and progress of chronic lung diseases. Due to limitations of conventional two-dimensional histological methods, the complexity and the detailed anatomy of the lung blood circulation might be overlooked. In this study, we demonstrate the practical use of optical serial block face imaging (SBFI), ex vivo microcomputed tomography (micro-CT), and nondestructive optical tomography for visualization and quantification of the pulmonary circulation's 3D architecture from macro- to micro-structural levels in murine lung samples. We demonstrate that SBFI can provide rapid, cost-effective, and label-free visualization of mouse lung macrostructures and large pulmonary vessels. Micro-CT offers high-resolution imaging and captures microvascular and (pre)capillary structures, with microstructural quantification. Optical microscopy techniques such as optical projection tomography (OPT) and light sheet fluorescence microscopy, allows noninvasive, mesoscopic imaging of optically cleared mouse lungs, still enabling 3D microscopic reconstruction down to the precapillary level. By integrating SBFI, micro-CT, and nondestructive optical microscopy, we provide a framework for detailed and 3D understanding of the pulmonary circulation, with emphasis on vascular pruning and rarefaction. Our study showcases the applicability and complementarity of these techniques for organ-level vascular imaging, offering researchers flexibility in selecting the optimal approach based on their specific requirements. In conclusion, we propose 3D-directed approaches for a detailed whole-organ view on the pulmonary vasculature in health and disease, to advance our current knowledge of diseases affecting the pulmonary vasculature.

Comparison of 3D BFFE and 3D TRANCE on pulmonary artery imaging with two T-SLIP placement strategies.

3D BFFE and TRANCE can provide a visualization of pulmonary vessels without injection of contrast agent. T-SLIP can observe a large area of vessels using an arterial spin labeling technique. 3D BFFE and TRANCE with two T-SLIP placement strategies were compared on pulmonary artery imaging. Ten male and thirteen female healthy volunteers were recruited in the present study. Each subject underwent non-contrast-enhanced pulmonary MRA. Four protocols were involved in the present study as follows: 3D BFFE with T-SLIP covering vena cava (VC) and right atrium and ventricle (RV), respectively; 3D TRANCE with T-SLIP covering VC and RV, respectively. The SNR were measured at eight ROIs, while CNR were measured at five ROIs. The number of visualized branch and image quality were analyzed by two radiologists. The differences of metrics among different imaging strategies were compared. SNR and CNR were compared between two T-SLIP placement strategies using a paired t-test. The branches number and image quality were compared between two T-SLIP placement strategies using a rank-sum test. The agreement of subjective assessment was conducted using a Kappa test. There were significant differences at all ROIs between TRANCE and BFEE with T-SLIP on RV (all P values <0.01). TRANCE with T-SLIP on RV exhibited a higher CNR at all five ROIs compared with BFFE with T-SLIP on RV. TRANCE with T-SLIP on RV performed better on the number of observed branches and image quality compared with BFFE with T-SLIP on RV. 3D TRANCE with T-SLIP on RV can provide a higher SNR and image quality among four MR protocols, and thus may be a potential non-contrast enhanced technique in the visualization of pulmonary artery.

From basic scientific research to the development of new drugs for pulmonary arterial hypertension: insights from activin-targeting agents.

Pulmonary arterial hypertension (PAH) is a severe disorder of the pulmonary vasculature leading to right ventricular failure. This pulmonary vascular remodelling leads to increased pulmonary vascular resistance and high pulmonary arterial pressures. Despite the development of new therapies, many patients continue to experience significant morbidity and mortality. This review offers a comprehensive overview of the current understanding of PAH pathophysiology, with a focus on key mechanisms that contribute to pulmonary endothelial cell dysfunction and the pathological accumulation of pulmonary artery smooth muscle cells, mesenchymal cells and inflammatory cells in the walls of remodelled small pulmonary vessels, three processes central to the progression of PAH. In particular, it highlights recent developments in targeting the activin signalling pathway, a novel therapeutic approach that shows promise in modulating these pathological processes. The review also addresses the ongoing challenges in translating preclinical findings into effective clinical treatments, emphasising the importance of integrating human data with preclinical models and adopting innovative strategies to bridge the gap between research and clinical practice.

Clinicolaboratory characteristics and 1-year survival among group 1 pulmonary hypertension in a university hospital

Abstract Background Pulmonary arterial hypertension is a life-threatening disorder of the pulmonary vascular system that can lead to right-sided heart failure, respiratory failure, and death. Still, more knowledge is needed to understand this complex disease. The study objective is to evaluate the clinicolaboratory characteristics of group 1 pulmonary hypertension patients and their survival in the Assiut University pulmonary hypertension unit throughout the study time. Patients and methods Consecutive patients were referred to the Assiut University Chest Department Pulmonary Hypertension unit in collaboration with the cardiology department for diagnosis and management. Patients were diagnosed as group 1 pulmonary hypertension (PH) included in the study. Patient demographic data, clinical presentation, electrocardiography, laboratory data, and invasive and noninvasive hemodynamics at presentation were recorded. The patients were followed through the study time to identify their survival. Results Out of 40 patients referred to the pulmonary hypertension unit throughout the study period, 29 patients have group 1 PH and were included. Their mean age was 44.10 ± 15.14 years, most of them were females (86.2%), 44.8% of patients presented with WHO functional class II, 48.3% of patients with FC III, and 6.9% of patients with FC IV. The mean 6 min walking distance was 256.97 ± 89.46 m. Pulmonary artery catheterization hemodynamic parameters were mean pulmonary artery pressure 52.48 ± 18.24 mmHg, pulmonary vascular resistance 13.32 ± 7.31 WU, cardiac index 2.32 ± 0.83 L/min/m2, and mixed venous oxygen saturation 59.6 ± 7%. The mean follow-up duration is 12.6 ± 8.8 months, and their survival at the end of study time was 82.35%. Serum uric acid, pulmonary vascular resistance, pulmonary artery systolic pressure, and age are predictors of disease progression and mortality. Conclusion Group 1 pulmonary hypertension is an uncommon complex disease with a difficult early diagnosis. Its clinical presentation varies from insidious breathlessness, syncope, palpitation, and obvious right heart failure. Some factors as serum uric acid, pulmonary vascular resistance, pulmonary artery systolic pressure, and age are associated with prognosis. One-year survival was 82.35%. Trial registration ClinicalTrials.gov ID: NCT0479145.

Histological investigation for the effect of non-steroidal anti-inflammatory drug [diclofenac] on myocardium and lung of local breed Rabbit

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesics, anti-inflammatory agents, and antipyretics. The goal of this study was to perform a histological assessment of therapeutic and overdose dosages of diclofenac on the heart and lung tissues and serum Troponin I, Lactate Dehydrogenase, and Creatine Kinase. Thirty local breed rabbits weighing 1000 and 1400 grams were used, divided into four groups: therapeutic group I, overdose group II, overdose group III, and control group. Each group was injected intraperitoneum with different doses of diclofenac (2, 20, 50 mg/kg) once daily for 20 days, while the control group was injected with normal saline. The results of heart sections in the experimental groups showed numerous histological alterations. In group I, muscle fibers were degenerated, lipid droplets within hemolyzed, and fibrinoid deposition in congested blood vessels. Group II showed a woven appearance of muscle fibers, atrophied muscle fibers, and an increased presence of fibroblasts between blood vessels and adjacent muscle fibers. In group III, colloid appearances, pavement of inflammatory cells on the tunica intima of a congested blood vessel, muscle fiber necrosis, and hemosiderin deposits were observed between muscle fibers. The lung results referred to that group I had thickened the interstitial connective tissue, hyperplasia in connective cells, and cytoplasmic vacuolation of type I alveolus cells. In group II, the results revealed folded alveolar walls, droplets in hemolyzed congested blood vessel, and aggregation of desquamated cells within the lumen of alveoli. Group III showed engorged pulmonary vessel, folded alveolar walls surrounded with inflammatory cells infiltration. The results of serum Troponin I, creatine kinase and Lactate dehydrogenase showed a significant increase in between the experimental group when compared with control group, otherwise, the results of Troponin I in group III showed a significant decrease when compared with the control group on level 0.05%. Finally, the results of serum cholesterol a significant increase in between experimental when compared with control group on level 0.05%.

Rapid adaptive regulation of systemic circulation is suppressed in pulmonary

Pulmonary arterial hypertension (PAH) is characterized by an increase of a pressure in the pulmonary circulation; PAH is accompanied by activation of the sympathetic (SNS) and the renin-angiotensin-aldosterone system (RAAS). However, PAH-associated changes in baroreceptor regulation of systemic circulation, which is tightly interwoven with SNS and RAAS, have not been studied. The baroreceptor response (BRR) was studied in a chronic monocrotaline (MCT) model of PAH in rats (Wistar, 290 ± 30 g, 2–4 months). Phenylephrine as an agonist of α1-adrenergic receptor and sodium nitroprusside as NO donor were gradually administered to chronically catheterized, non-anesthetized control animals and animals with PAH (4 weeks after MCT administration) to induce vasomotor responses. Mean arterial pressure and heart rate (HR) were recorded under the action of vasoactive compounds alone or under the action of vasoactive compounds in presence of angiotensin-II (ATII), atropine. The parameters characterizing baroreceptor change in HR including maximal and minimal heart rate (HRmax, HRmin), reflex tachycardia (TBRR) and bradycardia (BBRR), range (ABBR) and the baroreceptor response sensitivity index (SIBRR) were calculated. A significant decrease in HRmax, TBRR, ABBR (but not BBRR), as well as the sensitivity index of BRR was observed in rats with PAH. ATII induces significant and different changes in the BRR parameters in control rats and in rats with PAH if administered 4 weeks after the start of the experiment. In rats with PAH, ATII causes less pronounced changes in HRmax, TBRR, and BBRR than in control animals. ATII insignificantly affects parasympathetic component of the baroreceptor reflex in rats with PAH. Thus, at least in the MCT-mediated model in rats, PAH significantly deteriorates the baroreceptor regulation of HR. This effect manifests in a decrease in the range and sensitivity of the baroreceptor response. Also, PAH unequally affects the sympathetic and parasympathetic control of the baroreceptor regulation of HR. On the other hand, ATII exhibits weak ability to alter BRR in rats with HAP. In conclusion, PAH leads to a disfunction of immediate, reflex mechanisms HR and systemic circulation control.

Multimodal Screening for Pulmonary Arterial Hypertension in Systemic Scleroderma: Current Methods and Future Directions.

Systemic sclerosis (SSc) is an immuno-inflammatory rheumatic disease that can affect both the skin and internal organs through fibrosis. Pulmonary arterial hypertension (PAH) is one of the most severe secondary complications. Structural changes in the vascular bed lead to increased pressures in the pulmonary circulation, severely impacting the right heart and significantly affecting mortality. The gold standard for diagnosing PAH is right heart catheterization (RHC), an invasive method for measuring cardiac pressure. Due to the high risk of complications, procedural difficulties, and significant costs, non-invasive screening for SSc-PAH has garnered significant interest. Echocardiography is likely the most important screening tool, providing structural and functional information about the right heart through measurements that have proven their utility over time. In addition to imagistic investigations, serum biomarkers aid in identifying patients at risk for PAH and can provide prognostic information. Currently, well-known serum biomarkers (NT-proBNP, uric acid) are used in screening; however, in recent years, researchers have highlighted new biomarkers that can enhance diagnostic accuracy for SSc patients. Pulmonary involvement can also be assessed through pulmonary function tests, which, using established thresholds, can provide additional information and help select patients requiring RHC. In conclusion, given the invasiveness of RHC, non-invasive screening methods are particularly important for SSc patients.

Mechanical Circulatory Support for Massive Pulmonary Embolism.

Up to 50% of patients with pulmonary embolism (PE) experience hemodynamic instability and approximately 70% of patients who die of PE experience an accelerated cascade of symptoms within the first hours of onset of symptoms, thus necessitating rapid evaluation and intervention. Venoarterial extracorporeal membrane oxygenation and other ventricular assist devices, depending on the hemodynamic derangements present, may be used to stabilize patients with massive PE refractory to initial therapies or with contraindications to other interventions. Given the abnormalities in both pulmonary circulation and gas exchange caused by massive PE, venoarterial extracorporeal membrane oxygenation may be considered the preferred form of mechanical circulatory support for most patients. Venoarterial extracorporeal membrane oxygenation unloads the right ventricle and improves oxygenation, which may not only help buy time until definitive treatment but may also reduce myocardial ischemia and myocardial dysfunction. This review summarizes the available clinical data on the use of mechanical circulatory support, especially venoarterial extracorporeal membrane oxygenation, in the treatment of patients with massive PE. Furthermore, this review also provides practical guidance on the implementation of this strategy in clinical practice.

Quantification of the pulmonary vasculature in mice under chronic hypoxia with contrast-free pulmonary angiography in vivo imaging.

Innovative advancements in preclinical imaging have led to the development of cone-beam computed tomography (CBCT) combined with contrast-free pulmonary angiography (CFPA), a novel lung scanning technology capable of assessing lung function and pulmonary vascular morphology. This cutting-edge approach integrates CBCT to provide detailed quantification of the pulmonary vascular tree. The application of this technique to image and quantify changes in the pulmonary vascular tree of mice exposed to chronic hypoxia has not been investigated. In this study, we investigated the feasibility of utilizing CFPA for imaging changes in the murine lung vascular bed under chronic hypoxia and assessed whether vascular metrics correlate with hematologic parameters and/or right ventricular pressure and mass. Our results revealed a significant increase in hemoglobin and total pulmonary vascular blood volume, as well as total pulmonary vessel length following exposure to chronic hypoxia. The pulmonary vascular blood volume and total vessel length strongly correlated with hemoglobin. There was also an increase in pulmonary arterial pressure and right ventricular mass under hypoxia that was linked to the hematological response and the changes in the pulmonary vascular bed. These findings highlight the application of preclinical CBCT and CFPA imaging as a valuable tool for visual and quantitative analysis of the pulmonary vasculature in preclinical models of chronic hypoxia and its potential use in investigating other pulmonary vasculopathies.NEW & NOTEWORTHY Cone-beam computed tomography (CBCT) combined with contrast-free pulmonary angiography (CFPA) is a novel lung scanning technology capable of assessing pulmonary vascular morphology in vivo in murine models.

Health-Related Quality of Life among Patients with Ventricular Assist Devices in Saudi Arabia

Background: End-stage heart failure patients awaiting heart transplant often require Ventricular Assisted Devices (VAD) to support systemic and pulmonary circulation and to improve ventricular function, symptoms, and Health-Related Quality of Life (HRQoL). This study evaluates the health-related quality of life in patients with VAD and was conducted at the Cardio Ventricular Assisted Devices Clinic at King Faisal Specialist Hospital and Research Centre, Riyadh. Methods: This retrospective cohort study design included all eligible VAD patients who were still attending the cardio ventricular assisted devices clinic at KFSHRC, Riyadh. Each study participant was assigned a detailed questionnaire to assess and evaluate HRQoL outcomes measured in physical limitations, emotional stress, sexual activity, and social function from the date of device insertion to the time of data collection. Data were analyzed using the Statistical Package for Social Studies (SPSS 22; IBM Corp., New York, NY, USA). Results: Between February 2016 until June 2020, 26 patients were eligible for the study. The patients' support scores were moderate to high, indicating a positive effect on their HRQoL, with a mean score of 57.69 in emotional activity, a mean score of 34.07 in physical activity, and a mean score of 83.17 in social activity. The study's results show that the level of HRQoL varies among patients with VADs. Conclusion: Participating patients with VAD reported excellent health-related quality of life in all domains, with moderate to high support scores indicating a positive effect on their HRQoL. There is currently a lack of study on HRQoL in patients with VADs in Saudi Arabia. Therefore, this study may provide a baseline understanding of current challenges in the care of heart failure patients with VAD awaiting a heart transplant.