Explore the vast range of titles available.

Pulmonary fibrosis induced by repetitive chemical injury in mice involves cross talk among macrophages, endothelial cells and fibroblasts. Macrophages induce expression of the Notch ligand Jag1 in pulmonary capillary endothelial cells, leading to Notch pathway activation in perivascular fibroblasts and fibrosis. Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin–dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1 ) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis.

In recent years, the study of right ventricular (RV) to pulmonary circulation (PC) coupling in heart failure with preserved ejection fraction (HFpEF) has been a matter of special interest. Tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio has emerged as a reliable noninvasive index of RV to PC coupling. Thus, we hypothesized that TAPSE/PASP would be a predictor of readmission burden in HFpEF. One thousand one hundred and twenty seven consecutive HFpEF patients discharged for acute HF were included. In 367 patients (32.6%), PASP could not be accurately measured by echocardiography, leaving the final sample size to be 760 patients. Negative binomial regression method was used to evaluate the association between TAPSE/PASP ratio and recurrent admissions. Mean age of the cohort was 75.6 ± 9.7 years and 68.3% were women. At a median (interquartile range) follow-up of 2.0 (2.9) years, 352 (46.3%) patients died and 1,214 readmissions were registered in 482 patients (63.4%), being 506 of them HF-related. There was a stepwise increase in the rates of all-cause and HF readmissions by decreasing TAPSE/PASP ratio. After multivariable adjustment, TAPSE/PASP <0.36 was associated with a higher risk of HF-related recurrent admissions (incidence rate ratio [IRR] 1.51, 95% confidence interval [CI], 1.01 to 2.24; p = 0.040), whereas patients in the lowest quintile (TAPSE/PASP <0.28) exhibited the highest risk of both all-cause and HF-related recurrent admissions (IRR 1.40, 95% CI 1.04 to 1.87, p = 0.025; and IRR 1.85, 95% CI 1.22 to 2.80, p = 0.004, respectively). In conclusion, TAPSE/PASP ratio, as a noninvasive index of RV-PC coupling, emerges as a strong predictor of recurrent hospitalizations in HFpEF.

Background Management of pulmonary atresia with ventricular septal defect and ductal-dependent pulmonary circulation (PA/VSD/PDA) varies according to pulmonary artery morphology and institutional surgical strategy. We adopted a range of initial palliative surgical options for patients with PA/VSD/PDA and evaluated the effectiveness of our management strategy. Methods Twenty-five patients with PA/VSD/PDA were enrolled between May 2015 and July 2023. Patients with major aortopulmonary collateral arteries were excluded. The mean age at initial surgery was 14.9 ± 13.7 days, and the mean weight was 3.17 ± 0.35 kg. Twenty-two (88%) patients were neonates. Nineteen patients underwent initial palliative systemic-to-pulmonary shunt, while six underwent an initial definitive Rastelli operation depending on the main pulmonary artery morphology and branch pulmonary arteries size. Results One patient died of postoperative brain hemorrhage following the initial definitive Rastelli operation. The mean follow-up duration was 58.5 ± 28.4 months. During follow-up, one patient died suddenly two months after the initial central shunt procedure. All surviving patients with a shunt, except two, underwent biventricular repair: ten with the Rastelli operation and six with the transannular patch (TAP) procedure. The staged TAP group demonstrated a significantly larger freedom from reoperation rate than that of the initial Rastelli operation group ( p  = 0.022) and a significantly lower catheter-based reintervention rate than that of the other two management groups ( p  = 0.011). Conclusions A management strategy using an initial definitive Rastelli operation or systemic-to-pulmonary shunt based on main pulmonary artery development and branch pulmonary arteries size is safe and effective for PA/VSD/PDA treatment. The staged TAP procedure could be a viable option for patients with PA/VSD/PDA and a well-developed main pulmonary artery segment. Trial registration Not applicable. Graphical Abstract

The autonomic regulation of the pulmonary vasculature has been under‐appreciated despite the presence of sympathetic and parasympathetic neural innervation and adrenergic and cholinergic receptors on pulmonary vessels. Recent clinical trials targeting this innervation have demonstrated promising effects in pulmonary hypertension, and in this context of reignited interest, we review autonomic pulmonary vascular regulation, its integration with other pulmonary vascular regulatory mechanisms, systemic homeostatic reflexes and their clinical relevance in pulmonary hypertension. The sympathetic and parasympathetic nervous systems can affect pulmonary vascular tone and pulmonary vascular stiffness. Local afferents in the pulmonary vasculature are activated by elevations in pressure and distension and lead to distinct pulmonary baroreflex responses, including pulmonary vasoconstriction, increased sympathetic outflow, systemic vasoconstriction and increased respiratory drive. Autonomic pulmonary vascular control interacts with, and potentially makes a functional contribution to, systemic homeostatic reflexes, such as the arterial baroreflex. New experimental therapeutic applications, including pulmonary artery denervation, pharmacological cholinergic potentiation, vagal nerve stimulation and carotid baroreflex stimulation, have shown some promise in the treatment of pulmonary hypertension. What is the topic of this review? This review examines our understanding of the autonomic control of pulmonary circulation, with an emphasis on its clinical relevance and potential therapeutic targeting in pulmonary hypertension. What advances does it highlight? The sympathetic and parasympathetic nervous systems both regulate pulmonary vascular tone and stiffness, in integration with systemic autonomic homeostasis. Pulmonary vascular afferents responsive to pulmonary arterial pressure produce distinct pulmonary baroreflex responses. Dysfunction in autonomic control both to and from the pulmonary vasculature might contribute to pulmonary hypertension, and new approaches targeting this have demonstrated early success.

Background and aim Pulmonary thromboembolism (PTE) is a common cause of cardiovascular death worldwide. Due to its nonspecific clinical symptoms, PTE is easy to be missed or misdiagnosed. Pulmonary transit time (PTT) is a noninvasive cardiopulmonary hemodynamic index, which is the time required for a blood sample to pass through pulmonary circulation. This study is aim to establish a rabbit PTE model using auto-thrombus, evaluating the dynamic changes in a rabbit’s heart structure and function at multiple time points before and after modeling by echocardiography and exploring the application value of PTT obtained by contrast enhanced ultrasound (CEUS) in evaluating a PTE model. Methods Twenty-four healthy rabbits were intubated by femoral vein puncture to establish the PTE model. Echocardiography was performed before embolization, 2 h, 24 h, 3 days, 5 days, and 7 days after embolization to obtain conventional ultrasonic parameters. Then, CEUS was performed to obtain the PTT. Results Seventh day after modeling, nineteen rabbits were alive. Compared with pre-modeling, right heart parameters and heart rate in echocardiography were significantly impaired in the acute phase (2 and 24 h after modeling) and gradually returned to normal in the compensatory phase (3, 5, and 7 days after modeling). In contrast with conventional ultrasound parameters, PTT and nPTT revealed a gradually increasing trend at each time point. Receiver operating characteristic (ROC) curve analysis revealed with an extension of molding time, the area under the curve (AUC) of (n)PTT is larger and larger. Conclusions Right heart parameters obtained using conventional echocardiography can accurately indicate changes in the structure and function of the right heart during the acute phase of PTE, while (n)PTT measured by CEUS continues to extend during the acute and compensatory phases of PTE. Therefore, PTT (nPTT) obtained by CEUS is a useful clinical indicator for the diagnosis of PTE and can be utilized as a supplement to conventional echocardiography parameters. Graphical Abstract

There is limited knowledge of pulmonary physiology and pulmonary function after continuous flow-left ventricular assist device (CF-LVAD) implantation. Therefore, this study investigated whether CF-LVAD influenced pulmonary circulation by assessing pulmonary capillary blood volume and alveolar-capillary conductance in addition to pulmonary function in patients with heart failure. Seventeen patients with severe heart failure who were scheduled for CF-LVAD implantation (HeartMate II, III, Abbott, Abbott Park, IL or Heart Ware, Medtronic, Minneapolis, MN) participated in the study. They underwent pulmonary function testing (measures of lung volumes and flow rates) and unique measures of pulmonary physiology using a rebreathe technique that quantified the diffusing capacity of the lungs for carbon monoxide (DLCO) and diffusing capacity of the lungs for nitric oxide before and 3 months after CF-LVAD implantation. After CF-LVAD, pulmonary function was not significantly changed (p >0.05). For lung diffusing capacity, alveolar volume (VA) was not changed (p = 0.47), but DLCO was significantly reduced (p = 0.04). After correcting for VA, DLCO/VA showed a trend toward reduction (p = 0.08). For the alveolar-capillary component, capillary blood volume (Vc) was significantly reduced (p = 0.04), and alveolar-capillary membrane conductance trended toward a reduction (p = 0.06). However, alveolar-capillary membrane conductance/Vc was not altered (p = 0.92). In conclusion, soon after CF-LVAD implantation, Vc is reduced likely because of pulmonary capillary derecruitment, which contributes to the decrease in lung diffusing capacity.

Right ventricular assist devices (RVADs) have been extensively used to provide hemodynamic support for patients with end-stage right heart (RV) failure. However, conventional in-parallel RVADs can lead to an elevation of pulmonary artery (PA) pressure, consequently increasing the right ventricular (RV) afterload, which is unfavorable for the relaxation of cardiac muscles and reduction of valve complications. The aim of this study is to investigate the hemodynamic effects of the pulsatile frequency of the RVAD on pulmonary artery. Firstly, a mathematical model incorporating heart, systemic circulation, pulmonary circulation, and RVAD is developed to simulate the cardiovascular system. Subsequently, the frequency characteristics of the pulmonary circulation system are analyzed, and the calculated results demonstrate that the pulsatile frequency of the RVAD has a substantive impact on the pulmonary artery pressure. Finally, to verify the analysis results, the hemodynamic effects of the pulsatile frequency of the RVAD on pulmonary artery are compared under diffident support modes. It is found that the pulmonary artery pressure decreases by approximately 6% when the pulsatile frequency changes from 1 to 3 Hz. The increased pulsatile frequency of RA-PA support mode may facilitate the opening of the pulmonary valve, while the RV-PA support mode can more effectively reduce the load of RV. This work provides a useful method to decrease the pulmonary artery pressure during the RVAD supports and may be beneficial for improving myocardial function in patients with end-stage right heart failure, especially those with pulmonary hypertension.

Adverse events during the perinatal period are associated with an increased risk to develop cardiometabolic diseases later in life. We established a murine model to study long-term effects of perinatal hypoxia (PH) on the pulmonary circulation. We previously demonstrated that PH led to an impaired regulation of pulmonary vascular tone in adulthood, linked to alterations in K+ channels in males and in the nitric oxide (NO)/cyclic guanosine monophosphate pathway in females. Moreover, simultaneous administration of inhaled NO (iNO) during PH exposure prevented adverse effects of PH on adult pulmonary vasculature in females. The present study showed that PH induced a significant increase in right ventricular pressure in males and females, and an enhanced sensitivity to acute hypoxia in females. PH significantly reduced acetylcholine-induced relaxation in pulmonary artery, to a greater extent in females than in males. PH led to right ventricular hypertrophy in adulthood, appearing earlier in males than in females. Morphometric measurements showed a significant increase in the number of 25-75-µm pulmonary vessels in male lungs following PH, probably resulting in increased pulmonary vascular resistance. The effects of prolonged hypoxia in adulthood differed between males and females. Perinatal iNO during PH prevented PH-induced alterations in the cardiopulmonary system, whereas perinatal iNO alone could have some adverse effects. Therefore, PH led to long-lasting alterations in the regulation of adult pulmonary circulation, which vary between males and females. In males, the increased pulmonary vascular resistance was associated with morphological changes besides functional alterations, whereas females showed an important pulmonary vascular dysfunction.

Pulmonary hypertension (PH) is a fatal condition that affects many dogs. In humans, PH is often treated with beraprost sodium (BPS). However, the effectiveness of BPS for canine PH has not been established. This study aimed to evaluate the clinical and cardiovascular response of BPS in canine patients with PH of various causes. Sixteen dogs with PH (post-capillary PH, n = 8; pre-capillary PH, n = 8) were included. BPS was continuously administered twice daily at 15 µg/kg. All dogs underwent echocardiography, including speckle-tracking analysis and blood pressure measurement, before and after BPS administration. Continuous BPS administration (range: 13.2–22.0 µg/kg) significantly decreased the pulmonary and systemic vascular impedance and increased left and right ventricular myocardial strain. In dogs with post-capillary PH, BPS administration caused no significant worsening of the left atrial pressure indicators. No side effects of BPS were observed in any dog. BPS also improved cardiac function and pulmonary circulation through pulmonary vasodilation, suggesting that BPS may be an additional treatment option for canine PH of various causes. Particularly, BPS increased left ventricular function and systemic circulation without worsening the left heart loading condition in dogs with post-capillary PH.

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. COVID-19 severity is linked to microthrombus formation. Here, using an in vivo two-photon imaging technique in mice and human scRNA-Seq data, the authors show increased adhesion molecules on vascular neutrophils leading to platelet aggregation and reduced lung perfusion.