Pulmonary Circulation最新文献

Considering the beta-3 adrenoceptor agonist, mirabegron, may display vasodilator and cardioprotective properties, we investigated the therapeutic potential of mirabegron in monocrotaline-induced pulmonary hypertension in rats. High-dose mirabegron improved right ventricular function, and endothelium-dependent relaxation in isolated rat pulmonary arteries, suggesting that mirabegron may be beneficial in pulmonary arterial hypertension.

Early graft dysfunction following lung transplantation is commonly attributed to primary graft dysfunction (PGD). However, other rare etiologies may present with similar clinical and radiologic features. We report a unique case of a 58-year-old male with idiopathic pulmonary fibrosis who underwent bilateral lung transplantation. The donor was a young adult with traumatic brain injury. Within hours post-transplant, the recipient developed severe hypoxemia and diffuse infiltrates on chest imaging, consistent with Grade 3 PGD. Despite supportive therapy, there was limited improvement. Histopathological examination of transbronchial biopsies revealed cerebral cortical neurons and glial tissue embedded in the pulmonary vasculature, confirming cerebral tissue embolism. This case highlights cerebral tissue pulmonary embolism as an under-recognized cause of early allograft dysfunction. Clinicians should consider donor-derived embolic events, particularly in trauma-related donors, in the differential diagnosis of PGD-like presentations.

Total anomalous pulmonary venous connection (TAPVC) is a rare but life-threatening congenital heart defect that requires surgical correction. The sutureless technique has been developed as an alternative to conventional repair to minimize postoperative complications. This meta-analysis evaluates and compares the efficacy and safety of the two surgical approaches. A comprehensive literature search was conducted in PubMed, EMBASE, the Cochrane Library, and major Chinese databases for studies published between January 2010 and December 2024. Five retrospective comparative studies including a total of 1,327 patients met the inclusion criteria. Data were analyzed using RevMan version 5.4. Primary outcome measures included the incidence of postoperative pulmonary venous obstruction (PVO), reoperation due to PVO, total postoperative mortality, and late mortality. A random-effects model was applied to all analyses to account for anticipated clinical heterogeneity. A subgroup analysis based on TAPVC anatomical type was also performed. The meta-analysis demonstrated that the sutureless technique was associated with a significantly lower postoperative PVO rate (Odds Ratio [OR] = 0.46; 95% Confidence Interval [CI]: 0.28-0.77; p = 0.047) and a reduced reoperation rate due to PVO (OR = 0.25; 95% CI: 0.08-0.77; p = 0.049) compared with conventional surgery. Subgroup analysis indicated that the reduction in postoperative PVO was most evident among patients with infracardiac-type TAPVC. No statistically significant differences were observed in total postoperative mortality (OR = 0.66; 95% CI: 0.35-1.24; p > 0.05) or late mortality (OR = 0.37; 95% CI: 0.13-1.06; p > 0.05). Across all outcomes, heterogeneity was low to moderate (I² < 50%). Major limitations of this study include the retrospective design of all included studies, small sample sizes for certain analyses, variability in study methodology, and possible publication bias. The sutureless technique appears to be a safe and effective alternative to conventional surgery for primary TAPVC repair. It significantly reduces postoperative PVO and the need for reoperation, with the greatest benefit observed in high-risk subtypes such as infracardiac TAPVC. However, given that all available evidence is derived from retrospective studies of moderate quality, further large-scale prospective investigations are required to validate these findings and assess long-term outcomes.

The typical pathology of pulmonary hypertension (PH) is characterized by pulmonary vasoconstriction and irreversible pulmonary vascular remodeling. Vascular remodeling is the process of structural changes and cellular rearrangement of blood vessels due to injury and is a significant factor in conditions such as PH. Echinacoside (ECH) is a phenylethanol glycoside from Tibetan herbs, and our previous study found that ECH modulated calcium channels on pulmonary artery smooth muscle cells (PASMCs) and improved pulmonary vasoconstriction. To investigate the role of ECH in improving pulmonary vascular remodeling in PH, we constructed hypoxia-induced hypoxic pulmonary hypertension (HPH) and MCT-induced pulmonary arterial hypertension (PAH) models. Transcriptomic analysis revealed significant enrichment of Cav1.2, Cav3.2, and PKC/MAPK signaling pathways in PAH rats. ECH effectively inhibited Cav1.2 and Cav3.2 protein and mRNA expression, as well as the phosphorylation levels of PKC/MAPK, in HPH and PAH. In addition, ECH effectively reduced mean pulmonary artery pressure (mPAP) and right ventricular hypertrophy index (RVHI) and improved pulmonary vascular remodeling in HPH and PAH rats. In short, we found that ECH improved pulmonary vascular remodeling by modulating Cav1.2 and Cav3.2/PKC/MAPK pathways. Furthermore, this improvement was effective in both HPH and PAH.

There is a limited understanding of how pulmonary hypertension (PH) patients are managed worldwide. The Pulmonary Vascular Research Institute (PVRI) Innovative Drug Discovery Initiative (IDDI) global survey attempted to obtain insights into access to PH care in diverse international regions to pave future action plans. Responses from 151 centers (19.9% from Europe, 3.9% Middle East, 6% South Asia, 17.9% East Asia, 2% Sub-Saharan Africa, 31.8% Latin America, and 18.5% North America) were received. Most respondents had access to electrocardiography, echocardiography, and right heart catheterization but less availability to pulmonary function tests, ventilation/perfusion scans, and genetic testing. Phosphodiesterase type 5 (PDE-5) inhibitors were available in almost all centers but there was limited access to oral, inhaled, and parenteral prostacyclin therapy, riociguat, and selexipag. Cluster analysis of middle-high- and high income countries demonstrated significant variability in PH care delivery and disparities in therapeutic resources across the three clusters. The most common limitations identified that contribute to delayed PH diagnosis were insufficient financial resources, insufficient staff, and limited time. Survey respondents requested access to webinars with content experts (45%), access to content experts for consultation and review of complex cases via video chat (55%), resources to attend a conference (67.5%), and provision of a mentorship program (33.1%) along with greater availability of medications, remote conference access, clinical trial availability, and increased advocacy for patients. Survey results suggest significant disparities across the globe. Further research is needed to understand access to PH care and therapies in non-expert/academic centers and regional disparities within countries.

Chronic thromboembolic pulmonary hypertension (CTEPH) is due to unresolved pulmonary embolism (PE), however the pathophysiology of how PE evolves into CTEPH is unclear. Study of populations of acute PE patients at increased risk for CTEPH, such as those with prior splenectomy, may clarify the mechanisms driving transition from acute PE to CTEPH. In this study, we examined the relationship between acute PE, CTEPH and splenectomy in two observational cohorts. In the first, we compared the frequency of splenectomy among groups of patients with CTEPH, PE, and no PE. In the second, we compare clinical features of acute PE presentation in hospitalized patients with or without a prior splenectomy. We find that a history of splenectomy is significantly more frequent in patients with CTEPH than in patients with PE (OR 4.3, 95% CI 1.5-12.6). This association remained when we compared CTEPH patients to PE patients without a provoking factor for PE (OR 5.3, 95% CI 1.7-16.9), a population that is at increased risk of developing CTEPH. Patients with acute PE and prior splenectomy were more likely to present with subacute symptoms, more likely to have a distal location of PE, and less likely to have deep venous thrombosis (DVT) than were non-splenectomized acute PE patients. Thus, prior splenectomy appears to modify some clinical features of acute PE. We hypothesize that the difference in clinical features of PE that are observed in the context of prior splenectomy are relevant to the increased risk of CTEPH observed in this population.

This study evaluates the utility of CT-derived PA/A and RV/LV ratios in distinguishing surgically accessible CTEPH from acute PE and negative controls. Unlike the RV/LV ratio, PA/A ratio was significantly higher in CTEPH patients compared to low and intermediate/high-risk acute PE cohorts, indicating its utility as a marker of clot chronicity.

Schistosomiasis and sickle cell disease (SCD) both cause pulmonary hypertension (PH). We identified a subject with sickle cell trait and hepatosplenic schistosomiasis, who on right heart catheterization had PH, but due to high cardiac output. In a pre-clinical model, we found SCD mice were protected from developing schistosomiasis-induced PH.

In patients with pulmonary arterial hypertension (PAH), limited real-world data are available on persistence to oral treprostinil therapy, particularly while transitioning from parenteral prostacyclins. We compared persistence to oral treprostinil and total daily dose (TDD) achieved among patients with PAH initiating oral treprostinil de novo or while transitioning from parenteral prostacyclins using two real-world datasets: specialty pharmacy shipment records (Analysis 1) and ADAPT registry (Analysis 2). In Analysis 1, patients receiving oral treprostinil in 2017, 2020, and 2023 were included. In Analysis 2, de-identified data of patients enrolled in ADAPT from July 2017 to January 2022 were included. We conducted descriptive analyses and quantified persistence to oral treprostinil and TDD. In Analysis 1, the proportion of transition patients increased (24%-41%) from 2017 to 2023, whereas the proportion of de novo patients decreased (76%-59%). For the overall population, the mean initial oral treprostinil dose increased over the 3 years (6.0-8.9 mg TDD). The majority (61%) of patients transitioning to oral treprostinil were persistent with therapy at 12 months compared with de novo patients (47%). In Analysis 2, approximately 93% of transition patients and 77% of de novo patients were persistent on oral treprostinil therapy at 12 months. These analyses suggest that patients with PAH are increasingly being initiated on oral treprostinil while transitioning from parenteral prostacyclin rather than initiating de novo. Patients transitioning to oral treprostinil achieved and maintained higher TDD of oral treprostinil and persisted on oral treprostinil therapy longer than de novo patients.