Pulmonary Vasculature Research Articles

A real-world study evaluating the safety and utility of a two-row stapler reload on pulmonary vasculature.

Endoscopic staplers are common surgical devices used for the ligation and division of vasculature in thoracic procedures. When a stapler ligates and divides pulmonary vasculature, potentially catastrophic intraoperative bleeding at the staple-line may occur. The aim of this study was to confirm the safety and discuss the utility of a two-row stapler reload, by assessing the incidence of clinically necessary intraoperative hemostatic intervention when applied to pulmonary vasculature in real-world applications. This study was designed as a prospective non-comparative registry study conducted in seven centers across the United States, to confirm the safety and performance of Signia™ Small Diameter Reloads (SDR) when used for indicated thoracic surgical procedures. The primary endpoint was the incidence of hemostatic intervention related to the ligation and division of pulmonary arteries and veins. A five-point Likert scale scored hemostasis of each SDR staple-line. Secondary endpoints included the incidence of device-related only adverse events (AEs), device deficiencies, and procedure-related hospital readmission up to and including 30 days post operation. SDR was fired 302 times across pulmonary vasculature in 120 subjects. Three firings required clinically necessary hemostatic intervention for an intervention rate of 0.99% (3 of 302 firings). Moreover, 97.5% (117 of 120 subjects) had intact SDR staple-lines regardless of surgical access or stapler handle preference. Only 4 (3.3%) thoracoscopic and robotic procedures converted to open, but none were due to SDR staple-lines. There was no statistically significant difference between the Likert score of transected arteries compared to veins (P=0.61). There were no device deficiencies or device-only related AEs reported. In this study, the two-row stapler reloads demonstrated favorable safety and efficacy profiles when fired across hilar vessels in the thoracic space with a 99% hemostatic rate, independent of surgical access and stapler handle preference.

Omega-3 polyunsaturated fatty acids and pulmonary arterial hypertension: Insights and perspectives.

Pulmonary arterial hypertension (PAH) is a rare and progressive disorder that affects the pulmonary vasculature. Although recent developments in pharmacotherapy have extended the life expectancy of PAH patients, their 5-year survival remains unacceptably low, underscoring the need for multitarget and more comprehensive approaches to managing the disease. This should incorporate not only medical, but also lifestyle interventions, including dietary changes and the use of nutraceutical support. Among these strategies, n-3 polyunsaturated fatty acids (n-3 PUFAs) are emerging as promising agents able to counteract the inflammatory component of PAH. In this narrative review, we aim at analysing the preclinical evidence for the impact of n-3 PUFAs on the pathogenesis and the course of PAH. Although evidence for the role of n-3 PUFAs deficiencies in the development and progression of PAH in humans is limited, preclinical studies suggest that these dietary components may influence several aspects of the pathobiology of PAH. Further clinical research should test the efficacy of n-3 PUFAs on top of approved clinical management. These studies will provide evidence on whether n-3 PUFAs can genuinely serve as a valuable tool to enhance the efficacy of pharmacotherapy in the treatment of PAH.

Optimizing management of chronic pulmonary hypertension in preterm infants: strategies for a complex population.

Pulmonary hypertension (PH) is commonly observed in premature infants with bronchopulmonary dysplasia (BPD) and is associated with poor outcomes and increased mortality. This review explores the management of this intricate condition of the pulmonary vasculature, which exhibits heterogeneous effects and may involve both arterial and postcapillary components. Current management of BPD-PH should focus on optimizing ventilatory support, which involves treatment of underlying lung disease, transitioning to a chronic phase ventilation strategy and evaluation of the airway. Data on management is limited to observational studies. Diuretics are considered a part of the initial management, particularly in infants with right ventricular dilation. In many cases, pulmonary vasodilator therapy is required to induce pulmonary arterial vasodilation, reduce right ventricular strain, and prevent coronary ischemia and heart failure. Echocardiography plays a pivotal role in guiding treatment decisions and monitoring disease progression. BPD-PH confers a heightened risk of mortality and long-term cardio-respiratory adverse outcomes. Echocardiography has been advocated for screening, while catheterization allows for confirmation in select more complex cases. Successful management of BPD-PH requires a multidisciplinary approach, focusing on optimizing BPD treatment and addressing underlying pathologies.

Safety and Outcomes with Direct Oral Anticoagulants Versus Vitamin-K Antagonists in Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review, Meta-Analysis, and Meta-Regression.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary hypertension characterized by organized thrombi inside the pulmonary vasculature, leading to an increase in pulmonary artery pressure. CTEPH is seen in about 3-4% of patients with acute pulmonary embolism and is associated with poor outcomes. Apart from surgical intervention, lifelong anticoagulation is the mainstay of CTEPH management. Traditionally, CTEPH is managed with vitamin-K antagonists (VKA); however, direct oral anticoagulants (DOACs) are recently gaining popularity. However, the current literature comparing DOACs versus VKAs in CTEPH has inconsistent results. An electronic search of the major bibliographic databases was performed to retrieve studies comparing DOACs versus VKAs in CTEPH patients. For dichotomous outcomes, the odds ratio (ORs) with 95% confidence intervals (CI) were pooled using the DerSimonian and Laird random-effects model to generate forest plots. Statistical significance was considered at P < 0.05. Ten studies were included with 3936 patients (1269 in the DOAC group and 2667 in the VKA group). Treatment with DOAC was associated with no statistically significant difference in the risk of all-cause mortality (OR, 0.78; 95% CI, 0.35-1.71; P < 0.53), venous thromboembolism (OR, 1.19; 95% CI, 0.59-2.40; P = 0.63), major bleeding (OR, 0.68; 95% CI, 0.38-1.22; P = 0.20), and clinically relevant nonmajor bleeding (OR, 1.22; 95% CI, 0.80-1.86; P = 0.37). Our analysis demonstrates that DOACs are noninferior to VKAs in terms of their safety and outcomes profile in CTEPH. Further trials are needed to evaluate more robust evidence and to compare additional outcomes.

A Means to an End(othelium): Using Peripheral Blood Mononuclear Cell 'Omics to Peer into the Pulmonary Vasculature.

A Means to an End(othelium): Using Peripheral Blood Mononuclear Cell 'Omics to Peer into the Pulmonary Vasculature.

Preliminary Mechanism of Glial Maturation Factor β on Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.

Recent evidence suggests that glia maturation factor β (GMFβ) is important in the pathogenesis of pulmonary arterial hpertension (PAH), but the underlying mechanism is unknown. To clarify whether GMFβ can be involved in pulmonary vascular remodeling and to explore the role of the IL-6-STAT3 pathway in this process, the expression of GMFβ in PAH rats is examined and the expression of downstream molecules including periostin (POSTN) and interleukin-6 (IL-6) is measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The location and expression of POSTNis also tested in PAH ratsusing immunofluorescence. It is proved that GMFβ is upregulated in the lungs of PAH rats. Knockout GMFβ alleviated the MCT-PAH by reducing right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and pulmonary vascular remodeling. Moreover, the inflammation of the pulmonary vasculature is ameliorated in PAH rats with GMFβ absent. In addition, the IL-6-STAT3 signaling pathway is activated in PAH; knockout GMFβ reduced POSTN and IL-6 production by inhibiting the IL-6-STAT3 signaling pathway. Taken together, these findings suggest that knockout GMFβ ameliorates PAH in rats by inhibiting the IL-6-STAT3 signaling pathway.

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

In the field of pulmonary hypertension (PH), a well-established protocol to induce severe angioproliferation in rats (SuHx) involves combining the VEGF-R inhibitor Sugen 5416 (SU5416) with 3 wk of hypoxia (Hx). In addition, injecting monocrotaline (MCT) into rats can induce inflammation and shear stress in the pulmonary vasculature, leading to neointima-like remodeling. However, the SuHx protocol in mice is still controversial, with some studies suggesting it yields higher and reversible PH than Hx alone, possibly due to species-dependent hypoxic responses. To establish an alternative rodent model of PH, we hypothesized mice would be more sensitive to hemodynamic changes secondary to shear stress compared with Hx. We attempted to induce severe and irreversible PH in mice by combining SU5416 or monocrotaline pyrrole (MCTP) injection with pneumonectomy (PNx). However, our experiments showed SU5416 administered to mice at various time points after PNx did not result in severe PH. Similarly, mice injected with MCTP after PNx (MPNx) showed no difference in right ventricular systolic pressure or exacerbated pulmonary vascular remodeling compared with PNx alone. These findings collectively demonstrate that C57/B6 mice do not develop severe and persistent PH when PNx is combined with either SU5416 or MCTP.NEW & NOTEWORTHY We attempted to establish a mouse model of severe and irreversible pulmonary hypertension by substituting hypoxia with pulmonary overcirculation. To do so, we treated mice with either SU5416 or monocrotaline pyrrole after pneumonectomy and performed hemodynamic evaluations for PH. Despite this "two-hit" protocol, mice did not exhibit signs of severe pulmonary hypertension or exacerbated pulmonary vascular remodeling compared with PNx alone.

The effects of siRNA-mediated knockdown of AP-1 on pulmonary arterial and right ventricular dysfunction associated with cardiac and pulmonary fibrosis in cardiopulmonary disease

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Romania’s National Recovery and Resilience Plan, PNRR-III-C9-2022-I8, CF 93/15.11.2022, Financing Contract no. 760063/23.05.2023, and by the Romanian Academy Background Pulmonary hypertension (PH) is a complex multifactorial vascular pathology characterized by an increased pulmonary arterial pressure, vasoconstriction, remodelling of the pulmonary vasculature, thrombosis in situ and inflammation associated with right-side heart failure. Purpose Herein, we explored the potential beneficial effects of treatment with siRNA AP-1 on pulmonary arterial and right ventricular dysfunction and perivascular and interstitial fibrosis in pulmonary artery (PA), right ventricle (RV) and lung in an experimental animal model of monocrotaline (MCT)-induced pulmonary arterial hypertension. Methods Golden Syrian hamsters were divided into: (1) C group; (2) MCT group obtained by a single subcutaneous injection of 60 mg/kg MCT at the beginning of the experiment; (3) MCT- siRNA AP-1 group received a one-time subcutaneous dose of MCT and subcutaneous injections containing 100nM siRNA AP-1, every two weeks. All animal groups received water and standard chow ad libitum for 3 months. Results In comparison with the MCT group, siRNA AP-1 treatment had significant beneficial effects contributing to: (1) a reduction in TGF-β1/ET-1/IL-1β plasma concentrations; (2) a reduced level of cytosolic ROS production in PA, RV and lung, and ultrastructural improvements of these tissues; (3) a decrease of inflammatory and fibrotic marker expressions in PA (COL1A, Fibronectin, Vimentin, α-SMA, CTGF, Calponin, MMP-9), RV (COL1A, CTGF, Fibronectin, α-SMA, F-actin, OB-cadherin) and lung (COL1A, CTGF, Fibronectin, α-SMA, OB-cadherin), and an increase of endothelial marker expressions (CD31/VE-cadherin) in PA; (4) structural and functional recoveries of PA (reduced VTI/Vel, restored vascular response) and RV (enlarged internal cavity diameter in diastole, increased TAPSE/PRVOFs) associated with a decrease in systolic/diastolic blood pressure, and heart rate; (5) a reduced protein expression profile of AP-1S3/ pFAK/FAK/pERK/ERK and a significant decrease in the expression levels of miRNA-145, miRNA-210, miRNA-21, and miRNA-214 along with an increase of miRNA-124 and miRNA-204. Conclusion The siRNA AP-1-based therapy led to an improvement of pulmonary arterial and right ventricular function accompanied by a regression of perivascular and interstitial fibrosis in PA, RV and lung and a down-regulation of key inflammatory and fibrotic markers in MCT-treated hamsters.

Skeletal Muscle SIRT3 Deficiency Contributes to Pulmonary Vascular Remodeling in Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction.

Pulmonary hypertension (PH) is a major complication linked to adverse outcomes in heart failure with preserved ejection fraction (HFpEF), yet no specific therapies exist for PH associated with HFpEF (PH-HFpEF). We have recently reported on the role of skeletal muscle SIRT3 (sirtuin-3) in modulation of PH-HFpEF, suggesting a novel endocrine signaling pathway for skeletal muscle modulation of pulmonary vascular remodeling. Using skeletal muscle-specific Sirt3 knockout mice (Sirt3skm-/-) and mass spectrometry-based comparative secretome analysis, we attempted to define the processes by which skeletal muscle SIRT3 defects affect pulmonary vascular health in PH-HFpEF. Sirt3skm-/- mice exhibited reduced pulmonary vascular density accompanied by pulmonary vascular proliferative remodeling and elevated pulmonary pressures. Comparative analysis of secretome by mass spectrometry revealed elevated secretion levels of LOXL2 (lysyl oxidase homolog 2) in SIRT3-deficient skeletal muscle cells. Elevated circulation and protein expression levels of LOXL2 were also observed in plasma and skeletal muscle of Sirt3skm-/- mice, a rat model of PH-HFpEF, and humans with PH-HFpEF. In addition, expression levels of CNPY2 (canopy fibroblast growth factor signaling regulator 2), a known proliferative and angiogenic factor, were increased in pulmonary artery endothelial cells and pulmonary artery smooth muscle cells of Sirt3skm-/- mice and animal models of PH-HFpEF. CNPY2 levels were also higher in pulmonary artery smooth muscle cells of subjects with obesity compared with nonobese subjects. Moreover, treatment with recombinant LOXL2 protein promoted pulmonary artery endothelial cell migration/proliferation and pulmonary artery smooth muscle cell proliferation through regulation of CNPY2-p53 signaling. Last, skeletal muscle-specific Loxl2 deletion decreased pulmonary artery endothelial cell and pulmonary artery smooth muscle cell expression of CNPY2 and improved pulmonary pressures in mice with high-fat diet-induced PH-HFpEF. This study demonstrates a systemic pathogenic impact of skeletal muscle SIRT3 deficiency in remote pulmonary vascular remodeling and PH-HFpEF. This study suggests a new endocrine signaling axis that links skeletal muscle health and SIRT3 deficiency to remote CNPY2 regulation in the pulmonary vasculature through myokine LOXL2. Our data also identify skeletal muscle SIRT3, myokine LOXL2, and CNPY2 as potential targets for the treatment of PH-HFpEF.

Fibroblasts in Pulmonary Hypertension: Roles and Molecular Mechanisms.

Fibroblasts, among the most prevalent and widely distributed cell types in the human body, play a crucial role in defining tissue structure. They do this by depositing and remodeling extracellular matrixes and organizing functional tissue networks, which are essential for tissue homeostasis and various human diseases. Pulmonary hypertension (PH) is a devastating syndrome with high mortality, characterized by remodeling of the pulmonary vasculature and significant cellular and structural changes within the intima, media, and adventitia layers. Most research on PH has focused on alterations in the intima (endothelial cells) and media (smooth muscle cells). However, research over the past decade has provided strong evidence of the critical role played by pulmonary artery adventitial fibroblasts in PH. These fibroblasts exhibit the earliest, most dramatic, and most sustained proliferative, apoptosis-resistant, and inflammatory responses to vascular stress. This review examines the aberrant phenotypes of PH fibroblasts and their role in the pathogenesis of PH, discusses potential molecular signaling pathways underlying these activated phenotypes, and highlights areas of research that merit further study to identify promising targets for the prevention and treatment of PH.

Prevalence of Pulmonary Hypertension among Sudanese Patients with Sickle Cell Disease.

Sickle Cell Disease (SCD) is a hereditary condition characterized by aberrant red blood cell morphology, leading to persistent hemolytic anemia. The consequential impact of SCD on the pulmonary vasculature can result in pulmonary hypertension (PHT), a severe complication that detrimentally affects the well-being and survival of individuals with SCD. The prevalence and risk determinants of PHT in SCD patients exhibit variations across diverse geographical regions and populations. This study aims to ascertain the prevalence of PHT among Sudanese SCD patients and identify associated factors. A cohort of thirty-one adult sickle cell disease (SCD) patients, as confirmed by hemoglobin electrophoresis, were recruited for participation in this cross-sectional study. Comprehensive data encompassing demographic, clinical, and laboratory parameters were collected. Doppler echocardiography was employed to quantify pulmonary arterial systolic pressure (PASP) and evaluate right ventricular size and function. Within our cohort, the prevalence of PHT was 29%. Active cigarette smoking demonstrated a significant association with PHT (P=0.042), while hydroxyurea therapy exhibited no noticeable impact on PHT (P=0.612). Our investigation revealed a PHT prevalence of less than one-third in our SCD patient population, aligning with prior studies. Notably, independent of other factors, cigarette smoking emerged as a distinct risk factor for PHT in SCD patients. This highlights the potential utility of smoking cessation as an intervention to delay the onset of this condition. However, further research is imperative to elucidate the mechanisms through which smoking contributes to PHT development in individuals with SCD.

Adipose mesenchymal stem cells-derived exosomes attenuated hyperoxia-induced lung injury in neonatal rats via inhibiting the NF-κB signaling pathway.

Bronchopulmonary dysplasia (BPD) is the most common chronic morbidity in extremely preterm infants. Mesenchymal stem cells-derived exosomes (MSC-Exos) therapies have shown prospects in animal models of BPD. Our study aimed to evaluate the effect of adipose mesenchymal stem cells-derived exosomes (AMSC-Exos) on BPD and the role of theNF-κB signaling pathway in this process. The AMSCswere extracted and AMSC-Exos were isolated by ultracentrifugation method. Newborn rats were exposed to hyperoxia (90% O2) continuously for 7 days to establish a BPD model. The rats were treated with AMSC-Exos by intratracheal administration on postnatal day 4 (P4). Pulmonary morphology, pulmonary vasculature, inflammatory factors, and NF-κB were assessed. Hyperoxia-induced primary type II alveolar epithelial cells (AECIIs) and AMSC-Exos treatment with or without a pan-NF-κB inhibitor (PDTC) were established to explore the potential mechanism. Hyperoxia-exposed rats showed alveolar simplification with decreased radial alveolar countand increased mean linear intercept,low CD31, and vascular endothelial growth factorexpression, reduced microvessel density, increased the expression of TNF-α, IL-1β, and IL-6 and decreased the expression of IL-10, and induced NF-κB phosphorylation. AMSC-Exos protected the neonatal lung from the hyperoxia-induced arrest of alveolar and vascular development, alleviated inflammation, and inhibited NF-κB phosphorylation. Hyperoxia decreased viability, increased apoptosis, enhanced inflammation, and induced NF-κB phosphorylation of AECIIs but improved by AMSC-Exos, PDTC, or AMSC-Exos+PDTC. The effect of AMSC-Exos+PDTC in AECIIs was the same as AMSC-Exos, but more notable than PDTC alone. AMSC-Exos attenuated the hyperoxia-induced lung injury in neonatal rats by inhibiting the NF-κB signaling pathway partly.

Portopulmonary hypertension: peculiarities of diagnosis and treatment

Portopulmonary hypertension is defined as the development of pulmonary hypertension secondary to portal one. Its exact prevalence is difficult to determine due to the lack of routine screening in patients with portal hypertension. Hemodynamic changes associated with portal hypertension, including the hyperdynamic state, portosystemic shunts, and splanchnic vasodilation, cause significant disturbances in the pulmonary vasculature and play a key role in the pathogenesis of the disease. Without treatment, portopulmonary hypertension leads to progressive right ventricular failure with a poor prognosis. Although Doppler echocardiography is the best initial screening tool for symptomatic patients and candidates for liver transplant, right heart catheterization remains the gold standard for disease diagnosis. Treatment of patients with portopulmonary hypertension is aimed at improving cardiac function, reducing pulmonary vascular resistance, and optimizing functional capacity. Pulmonary hypertension-specific therapy, which includes prostacyclin and its receptor agonists, endothelin receptor antagonists, phosphodiesterase inhibitors, and guanylate cyclase stimulators, plays a key role in the treatment of patients with portopulmonary hypertension. Small uncontrolled and recent single randomized controlled trials have reported promising results of vasodilator therapy in terms of clinical and hemodynamic improvement in patients, allowing certain patients to undergo liver transplantation. This review discusses the epidemiology, approach to diagnosis and treatment of patients with portopulmonary hypertension. We used MEDLINE database on the PubMed platform and the Cochrane library to search for literature sources using the keywords: portopulmonary hypertension, portal hypertension, pulmonary hypertension, liver cirrhosis, pulmonary complications.

The diverging roles of insulin-like growth factor binding proteins in pulmonary arterial hypertension

Pulmonary hypertension (PH) is a progressive, severe and to date not curable disease of the pulmonary vasculature. Alterations of the insulin-like growth factor 1 (IGF-1) system are known to play a role in vascular pathologies and IGF-binding proteins (IGFBPs) are important regulators of the bioavailability and function of IGFs. In this study, we show that circulating plasma levels of IGFBP-1, IGFBP-2 and IGFBP-3 are increased in idiopathic pulmonary arterial hypertension (IPAH) patients compared to healthy individuals. These binding proteins inhibit the IGF-1 induced IGF-1 receptor (IGF1R) phosphorylation and exhibit diverging effects on the IGF-1 induced signaling pathways in human pulmonary arterial cells (i.e. healthy as well as IPAH-hPASMCs, and healthy hPAECs). Furthermore, IGFBPs are differentially expressed in an experimental mouse model of PH. In hypoxic mouse lungs, IGFBP-1 mRNA expression is decreased whereas the mRNA for IGFBP-2 is increased. In contrast to IGFBP-1, IGFBP-2 shows vaso-constrictive properties in the murine pulmonary vasculature. Our analyses show that IGFBP-1 and IGFBP-2 exhibit diverging effects on IGF-1 signaling and display a unique IGF1R-independent kinase activation pattern in human pulmonary arterial smooth muscle cells (hPASMCs), which represent a major contributor of PAH pathobiology. Furthermore, we could show that IGFBP-2, in contrast to IGFBP-1, induces epidermal growth factor receptor (EGFR) signaling, Stat-3 activation and expression of Stat-3 target genes. Based on our results, we conclude that the IGFBP family, especially IGFBP-1, IGFBP-2 and IGFBP-3, are deregulated in PAH, that they affect IGF signaling and thereby regulate the cellular phenotype in PH.

Balloon Pulmonary Angioplasty for the Treatment of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension is a rare form of pulmonary hypertension in patients who have evidence of chronic thromboembolic occlusion of the pulmonary vasculature. Historically, surgical pulmonary thromboendarterectomy has been the treatment of choice. However, with up to 40% of patients deemed inoperable, balloon pulmonary angioplasty has emerged as an additional treatment strategy. Balloon pulmonary angioplasty is a complementary strategy alongside surgical pulmonary thromboendarterectomy and offers the opportunity for pulmonary revascularization in patients who have more distal disease, higher comorbidities, or residual obstruction following operative intervention. This review examines the history of balloon pulmonary angioplasty, highlights its effectiveness, discusses important complications and risk reduction strategies, and emphasizes the importance of centers forming a multidisciplinary team of providers to manage the complexity of patients with chronic thromboembolic pulmonary hypertension.

Respiratory Assist Devices in Pulmonary Rehabilitation.

Patients with advanced lung disease, especially patients with COPD, suffer from dyspnea at rest that worsens during the performance of even limited physical activities. The causes of dyspnea are multifactorial and are related to structural changes found in the parenchymal compartment of the lung as well as the airway and pulmonary vasculature. Alterations in any of the lung compartments may have negative consequences for the physiological performance of exercise. Respiratory assist devices that attenuate the pathophysiological derangements induced by the underlying lung disease, and/or unload the increased work of breathing, can enhance the performance of exercise, and help to produce more robust training effects in patients with lung disease. Herein we review the data that examines these approaches using respiratory assist devices to improve exercise outcomes in patients with COPD.

The acute effect of inhaled nitric oxide on the exercise capacity of patients with advanced interstitial lung disease: a randomized controlled trial

BackgroundInhaled nitric oxide (iNO) selectively acts on the pulmonary vasculature of ventilated lung tissue by reducing pulmonary vascular resistance and intrapulmonary shunt. This effect may reduce ventilation/perfusion mismatch and decrease pulmonary hypertension in patients with interstitial lung disease.MethodsIn a prospective, single-blinded, randomized, placebo-controlled trial, participants with advanced interstitial lung disease, underwent two separate six-minute walk tests (6MWT): one with iNO and the other with a placebo. The primary outcome measured the difference in meters between the distances covered in the two tests. Secondary outcomes included oxygen saturation levels, distance-saturation product, and Borg dyspnea score. A predefined subgroup analysis was conducted for patients with pulmonary hypertension.ResultsOverall, 44 patients were included in the final analysis. The 6MWT distance was similar for iNO treatment and placebo, median 362 m (IQR 265-409) vs 371 m (IQR 250-407), respectively (p = 0.29). Subgroup analysis for patients with pulmonary hypertension showed no difference in 6MWT distance with iNO and placebo, median 339 (256-402) vs 332 (238-403) for the iNO and placebo tests respectively (P=0.50). No correlation was observed between mean pulmonary artery pressure values and the change in 6MWT distance with iNO versus placebo (spearman correlation Coefficient 0.24, P=0.33).ConclusionIn patients with advanced interstitial lung disease, both with and without concurrent pulmonary hypertension, the administration of inhaled nitric oxide failed to elicit beneficial effects on the six-minute walk distance and oxygen saturation. The use of inhaled NO was found to be safe and did not lead to any serious side effects.Trial registration(NCT03873298, MOH_2018-04-24_002331).

Pulmonary arteries in coelacanths shed light on the vasculature evolution of air-breathing organs in vertebrates

To date, the presence of pulmonary organs in the fossil record is extremely rare. Among extant vertebrates, lungs are described in actinopterygian polypterids and in all sarcopterygians, including coelacanths and lungfish. However, vasculature of pulmonary arteries has never been accurately identified neither in fossil nor extant coelacanths due to the paucity of fossil preservation of pulmonary organs and limitations of invasive studies in extant specimens. Here we present the first description of the pulmonary vasculature in both fossil and extant actinistian, a non-tetrapod sarcopterygian clade, contributing to a more in-depth discussion on the morphology of these structures and on the possible homology between vertebrate air-filled organs (lungs of sarcopterygians, lungs of actinopterygians, and gas bladders of actinopterygians).

Changes in the pulmonary circulation due to gravitational loads in high altitude conditions.

The impact of gravity on the existence of all living things has long been of interest to scientists. The force of the Earth's gravity combined with hypoxia significantly affects blood circulation and blood accumulation in various parts of the human and animal body. To date, the relationship between body position and blood circulation in pulmonary circulation under hypobaric hypoxia has not been sufficiently studied. Therefore, the research aims to determine the possibility of changing the body position in space on the reactions in the pulmonary circulation in the plains and highlands. For this purpose, research was conducted on male Wistar rats, 44 of whom spent 150 days at an altitude of 3200 m above sea level, and 25 representatives of the control group - at an altitude of 164 m. The study revealed that gravitational redistribution of blood in mountainous conditions is less pronounced compared to the control group. This is explained by the remodeling of the vascular wall and an increase in its stiffness. It was found that a change in pulmonary artery pressure at the time of a change in body position was recorded both on the plains and in the highlands. On the plains, when the body position of rats was changed to passive orthostatic, a decrease in systolic and diastolic pulmonary artery pressure was noted, and when the body position was changed to passive anti-orthostatic, an increase in pulmonary artery pressure was observed. The increase in pulmonary artery pressure was a compensatory mechanism due to the increased stiffness of the pulmonary vasculature. The practical significance of this research is to expand the understanding of the pathogenesis of pulmonary hypertension in high-altitude hypoxia.

Nexplanonectomy—the surgical removal of an embolized implanted contraceptive device: a case report and review of the literature

BackgroundNexplanon implants are a common hormonal contraceptive modality. Though rare, these devices can embolize into the injured wall of the basilic vein, through the right heart, and finally wedge itself into a pulmonary artery. With adherence to the arterial wall over time, it becomes less amenable to endovascular retrieval. Patients may present with symptoms mimicking a pulmonary embolism, or without any symptoms at all. In asymptomatic cases, endovascular retrieval and/or surgery is required when patients wish to begin having children prior to biological inactivity. The current literature showed as little as nine case reports detailing lung tissue removal in the aim of reversing a patient’s implanted contraceptive device.Case presentationA 22-year-old asymptomatic active-duty Caucasian female presented for elective outpatient Nexplanon removal. The suspicion of possible implant migration arose when it was discovered to be non-palpable in her left arm. After plain film x-rays failed to localize the implant, a chest x-ray and follow-up Computed Tomography (CT) scan revealed that the Nexplanon had migrated to a distal branch of the left pulmonary artery. Due to the patient’s strong desires to begin having children, the decision was made for removal. Initial endovascular retrieval failed due to Nexplanon encapsulation within the arterial wall. Ultimately, the patient underwent a left video-assisted thoracoscopic surgery (VATS) for exploration and left lower lobe basilar S7–9 segmentectomy, which successfully removed the Nexplanon.ConclusionsImplanted contraceptive devices can rarely result in migration to the pulmonary vasculature. These radiopaque devices are detectable on imaging studies if patients and clinicians are unable to palpate them. An endovascular approach should be considered first to spare lung tissue and avoid chest-wall incisions, but can be complicated by encapsulation and adherence to adjacent tissue. A VATS procedure with single-lung ventilation via a double-lumen endotracheal tube allows surgeons to safely operate on an immobilized lung while anesthesiologists facilitate single-lung ventilation. This patient’s case details the uncommon phenomenon of Nexplanon migration, and the exceedingly rare treatment resolution of lung resection to remove an embolized device.