RESUMO
OBJECTIVE: Total cavo-pulmonary connection (TCPC) is a palliative treatment for single ventricular malformations. For high-risk patients (preoperative mean pulmonary arterial pressure, mPAP > 15 mmHg), between the inhaled and oral targeted medications, the application of intravenous treprostinil as a bridge therapy to achieve "seamless" management is core postoperative treatment. This study intends to explore the effect of different administration regimens on early postoperative recovery. METHODS: This was a retrospective cohort study. High-risk pediatric patients (age ≤ 14 years) who underwent TCPC procedure in Fu Wai Hospital from 2015 to 2022 were included. Since the regimen of treprostinil was standardized in our center in 2021, the patients in 2020 and before were included in group 1, patients in 2021 and 2022 were included in group 2. The hemodynamic parameters were compared before and after the maintenance dose of treprostinil. The differences of demographic characteristics, surgical data and postoperative recovery were compared between the two groups. RESULTS: A total of 51 pediatric patients were included. Group 1 included 35 patients who received treprostinil at 1-3 postoperative days and an average dose of 12 ± 4 ng/(kg·min). Group 2 included 16 patients who received treprostinil within postoperative 1 day and an average dose of 22 ± 7 ng/(kg·min). There were no significant differences between the two groups in terms of age, weight, preoperative percutaneous oxygen saturation and mPAP, heterotaxy syndrome, TCPC procedure type, other concurrent procedure, cardiopulmonary bypass time and aortic cross-clamp proportion (p > 0.05). After 24 h of treprostinil treatment, the mPAP in group 1 reduced from 17 ± 3 mmHg to 15 ± 2 mmHg (p < 0.001), and in group 2 from 17 ± 2 mmHg to 14 ± 2 mmHg (p < 0.001), with no difference between groups. In the postoperative recovery, patients in Group 2 exhibited a reduced duration of mechanical ventilation, 19 (11, 25) hours vs 69 (23, 189) hours, p = 0.001; a shorter stay in the ICU, 8 (6, 12) days vs 16 (9,26) days, p = 0.006; and a shorter postoperative length of stay, 27 (17,55) days vs 39 (29,58) days, p = 0.032. Patients in Group 2 also exhibited a lower incidence of thromboembolic events, 0 (0/26) vs 26% (9/35), p = 0.043; and the need for renal replacement therapy, 0 (0/26) vs 31% (11/35), p = 0.011. CONCLUSION: Treprostinil reduces pulmonary artery pressure after TCPC procedure. The standardized application of treprostinil may improve the postoperative recovery which should be proven by randomized controlled trials or matched cohort studies in the future.
Assuntos
Anti-Hipertensivos , Epoprostenol , Hipertensão Arterial Pulmonar , Humanos , Epoprostenol/análogos & derivados , Epoprostenol/administração & dosagem , Epoprostenol/uso terapêutico , Feminino , Masculino , Estudos Retrospectivos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Criança , Pré-Escolar , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/cirurgia , Adolescente , Lactente , Administração Intravenosa , Cardiopatias Congênitas/cirurgia , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Técnica de Fontan/métodos , Técnica de Fontan/efeitos adversosRESUMO
INTRODUCTION: Pyroptosis, inflammatory necrosis of cells, is a programmed cell death involved in the pathological process of diseases. Endoplasmic reticulum stress (ERS), as a protective stress response of cell, decreases the unfold protein concentration to inhibit the unfold protein agglutination. Whereas the relationship between endoplasmic reticulum stress and pyroptosis in pulmonary hypertension (PH) remain unknown. Previous evident indicated that circular RNA (circRNA) can participate in several biological process, including cell pyroptosis. However, the mechanism of circRNA regulate pyroptosis of pulmonary artery smooth muscle cells through endoplasmic reticulum stress still unclear. Here, we proved that circSSR1 was down-regulate expression during hypoxia in pulmonary artery smooth muscle cells, and over-expression of circSSR1 inhibit pyroptosis both in vitro and in vivo under hypoxic. Our experiments have indicated that circSSR1 could promote host gene SSR1 translation via m6A to activate ERS leading to pulmonary artery smooth muscle cell pyroptosis. In addition, our results showed that G3BP1 as upstream regulator mediate the expression of circSSR1 under hypoxia. These results highlight a new regulatory mechanism for pyroptosis and provide a potential therapy target for pulmonary hypertension. METHODS: RNA-FISH and qRT-PCR were showed the location of circSSR1 and expression change. RNA pull-down and RIP verify the circSSR1 combine with YTHDF1. Western blotting, PI staining and LDH release were used to explore the role of circSSR1 in PASMCs pyroptosis. RESULTS: CircSSR1 was markedly downregulated in hypoxic PASMCs. Knockdown CircSSR1 inhibited hypoxia induced PASMCs pyroptosis in vivo and in vitro. Mechanistically, circSSR1 combine with YTHDF1 to promote SSR1 protein translation rely on m6A, activating pyroptosis via endoplasmic reticulum stress. Furthermore, G3BP1 induce circSSR1 degradation under hypoxic. CONCLUSION: Our findings clarify the role of circSSR1 up-regulated parental protein SSR1 expression mediate endoplasmic reticulum stress leading to pyroptosis in PASMCs, ultimately promoting the development of pulmonary hypertension.
Assuntos
Estresse do Retículo Endoplasmático , Miócitos de Músculo Liso , Artéria Pulmonar , Piroptose , Estresse do Retículo Endoplasmático/fisiologia , Piroptose/fisiologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Animais , Camundongos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , RNA Circular/metabolismo , RNA Circular/genética , Masculino , Células Cultivadas , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/genética , Proteínas de MembranaRESUMO
Connective tissue diseases-related pulmonary arterial hypertension (CTD-PAH) is a disease characterized by an elevated pulmonary artery pressure that arises as a complication of connective tissue diseases. The number of patients with CTD-PAH accounts for 25.3% of all PAH patients. The main pathological features of CTD-PAH are thickening of intima, media and adventitia of pulmonary arterioles, increased pulmonary vascular resistance, autoimmune activation and inflammatory reaction. It is worth noting that abnormal immune activation will produce autoantibodies and release cytokines, and abnormal immune cell recruitment will promote inflammatory environment and vascular remodeling. Therefore, almost all forms of connective tissue diseases are related to PAH. In addition to general therapy and targeted drug therapy for PAH, high-dose glucocorticoid combined with immunosuppressant can quickly alleviate and stabilize the basic CTD-PAH disease. Given this, the development of therapeutic approaches targeting immune dysregulation and heightened inflammation is recognized as a promising strategy to prevent or reverse the progression of CTD-PAH. This review explores the potential mechanisms by which immune cells contribute to the development of CTD-PAH and examines the clinical application of immunosuppressive therapies in managing CTD-PAH.
Assuntos
Doenças do Tecido Conjuntivo , Hipertensão Arterial Pulmonar , Humanos , Doenças do Tecido Conjuntivo/imunologia , Doenças do Tecido Conjuntivo/complicações , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/imunologia , Hipertensão Arterial Pulmonar/tratamento farmacológico , Animais , Imunossupressores/uso terapêutico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/imunologia , Hipertensão Pulmonar/tratamento farmacológicoRESUMO
OBJECTIVE: Interstitial lung diseases (ILDs) are diverse pulmonary disorders marked by diffuse lung inflammation and fibrosis. The variability in characteristics and treatment approaches complicates diagnosis and management. In advanced cases requiring transplantation, determining indications and selecting suitable candidates presents additional challenges. METHODS: Of all patients with non-IPF ILD between December 2016 to December 2022 were analyzed retrospectively. Patients were categorized into two groups: transplanted patients and deceased patients on the waiting list. Clinical data and survival outcomes were compared between groups. RESULTS: Of the 43 patients, 20 underwent lung transplantation while 23 died awaiting transplantation. Waiting list mortality was 53.4%, with median waiting times similar between groups (3 months for transplant patients and 6 months for those on the waiting list). There were no significant differences between groups in age, gender, height, BMI, 6-minute walk test (6MWT), or forced vital capacity (FVC). The prevalence of pulmonary hypertension (PH) was 76.7% in right heart catheterizations, similar in both groups. One single and 19 bilateral lung transplants were performed. Overall, 13 of the 20 patients survived to discharge from the hospital. One-year mortality was 7/20 (35%). The median follow-up was 34 months, with a 1-year conditional survival of 90.9% at 3 years and 70.7% at 5 years. CONCLUSIONS: This study underscores the importance of further research into non-IPF ILDs. Lung transplantation remains a viable option that can significantly enhance both the quality and longevity of life for patients with advanced ILD.
Assuntos
Doenças Pulmonares Intersticiais , Transplante de Pulmão , Listas de Espera , Humanos , Feminino , Masculino , Doenças Pulmonares Intersticiais/cirurgia , Doenças Pulmonares Intersticiais/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Listas de Espera/mortalidade , Adulto , Idoso , Hipertensão Pulmonar/cirurgia , Hipertensão Pulmonar/mortalidade , Capacidade VitalRESUMO
BACKGROUND Adult-onset Still's disease (AOSD) is a rare multisystem inflammatory disorder with a highly variable clinical presentation. Pulmonary complications of AOSD most commonly include pleural effusion and transient pulmonary infiltrates. In extremely rare cases, pulmonary arterial hypertension (PAH) develops as a complication. We present the case of a 49-year-old woman with adult-onset Still's disease presenting with fever, dyspnea, and pleuritic chest pain who was diagnosed with PAH. CASE REPORT A 49-year-old woman with a history of adult-onset Still's disease presented to the Emergency Department due to 1 week of fever, dyspnea, and pleuritic chest pain. Imaging, cardiac, immunologic, and infectious workups were performed and detected elevated inflammatory markers. She then underwent right-heart catheterization, which revealed high pulmonary artery pressure (PAP) and mean PAP at 43/18 mmHg and 27 mmHg, respectively. The patient was stabilized and discharged for further management of heart failure with preserved ejection fraction, and group 1 pulmonary arterial hypertension secondary to Still's disease. CONCLUSIONS Pulmonary complications of adult-onset Still's disease, such as PAH, are rare but potentially life-threatening. The treatment of PAH in adult-onset Still's disease involves the use of pulmonary vasodilators, immunosuppressive therapy, and regular monitoring to assess the prognosis of PAH. Our case report highlights the importance of considering PAH in patients with adult-onset Still's disease who present with dyspnea, fatigue, and chest pain. Increased clinician awareness of this extremely rare complication of AOSD can assist with rapid identification and improved patient outcomes.
Assuntos
Hipertensão Arterial Pulmonar , Doença de Still de Início Tardio , Humanos , Doença de Still de Início Tardio/complicações , Doença de Still de Início Tardio/diagnóstico , Feminino , Pessoa de Meia-Idade , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Pulmonar/etiologia , Cateterismo CardíacoRESUMO
BACKGROUND: Pulmonary hypertension is a condition that involves the remodeling of the right ventricle. Ongoing remodeling is also associated with disease prognosis. During the restructuring process, complex changes such as hypertrophy and dilatation may also be reflected in electrocardiographic parameters. OBJECTIVES: Our study aimed to investigate the relationship between prognosis and electrocardiographic parameters in patients with pulmonary arterial hypertension. METHODS: The study was designed retrospectively and included patients diagnosed with pulmonary arterial hypertension between 2010 and 2022. The patients were divided into two groups based on their survival outcome. Various parameters, including electrocardiographic, demographic, echocardiographic, catheter, and blood parameters, were compared between the two groups. A p-value of <0.05 was considered statistically significant. RESULTS: In the multivariate Cox analyses, the parameters that were found to be independently associated with survival were the 6-minute walk test, mean pulmonary artery pressure, presence of pericardial effusion, and time between the beginning of the QRS and the peak of the S wave (RS time) (p<0.05 for each). Of all the parameters, RS time demonstrated the best diagnostic performance (AUC:0.832). In the survival analysis, a significant correlation was found between RS time and survival when using a cut-off value of 59.5 ms (HR: 0.06 [0.02-0.17], p < 0.001). CONCLUSIONS: According to the results of our study, a longer RS time is associated with poor prognosis in patients with pulmonary arterial hypertension. We can obtain information about the course of the disease with a simple, non-invasive parameter.
FUNDAMENTO: A hipertensão pulmonar é uma condição que envolve a remodelação do ventrículo direito. A remodelação contínua também está associada ao prognóstico da doença. Durante o processo de reestruturação, alterações complexas como hipertrofia e dilatação também podem se refletir nos parâmetros eletrocardiográficos. OBJETIVOS: Nosso estudo teve como objetivo investigar a relação entre prognóstico e parâmetros eletrocardiográficos em pacientes com hipertensão arterial pulmonar. MÉTODOS: O estudo foi desenhado retrospectivamente e incluiu pacientes com diagnóstico de hipertensão arterial pulmonar entre 2010 e 2022. Os pacientes foram divididos em dois grupos com base no resultado de sobrevida. Vários parâmetros, incluindo parâmetros eletrocardiográficos, demográficos, ecocardiográficos, de cateter e sanguíneos, foram comparados entre os dois grupos. Um valor de p <0,05 foi considerado estatisticamente significativo. RESULTADOS: Na análise multivariada de Cox, os parâmetros que se mostraram independentemente associados à sobrevida foram o teste de caminhada de 6 minutos, pressão média da artéria pulmonar, presença de derrame pericárdico e tempo entre o início do QRS e o pico da onda S (tempo de RS) (p<0,05 para cada). De todos os parâmetros, o tempo de RS demonstrou o melhor desempenho diagnóstico (AUC: 0,832). Na análise de sobrevida, foi encontrada correlação significativa entre o tempo de RS e a sobrevida ao utilizar o valor de corte de 59,5 ms (HR: 0,06 [0,02-0,17], p < 0,001). CONCLUSÕES: De acordo com os resultados do nosso estudo, um tempo de RS mais longo está associado a um pior prognóstico em pacientes com hipertensão arterial pulmonar. Podemos obter informações sobre o curso da doença com um parâmetro simples e não invasivo.
Assuntos
Eletrocardiografia , Humanos , Feminino , Masculino , Prognóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Fatores de Tempo , Ecocardiografia , Hipertensão Arterial Pulmonar/fisiopatologia , Hipertensão Arterial Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/mortalidade , Idoso , Valores de Referência , Teste de CaminhadaRESUMO
BACKGROUND: There are limited data assessing the spectrum of systemic sclerosis-associated pulmonary hypertension (PH). METHODS: Data for 912 systemic sclerosis patients assessed between 2000 and 2020 were retrieved from the Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre (ASPIRE) registry and classified based on 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines and multimodality investigations. RESULTS: Reduction in pulmonary vascular resistance (PVR) diagnostic threshold to >2WU resulted in a 19% increase in precapillary PH diagnoses. Patients with PVR ≤2WU had superior survival to PVR >2-3WU which was similar to PVR >3-4WU. Survival in pulmonary arterial hypertension (PAH) was superior to PH associated with lung disease. However, patients with mild parenchymal disease on CT had similar characteristics and outcomes to patients without lung disease. Combined pre- and postcapillary PH had significantly poorer survival than isolated postcapillary PH. Patients with mean pulmonary arterial wedge pressure (PAWP) 13-15 mm Hg had similar haemodynamics and left atrial volumes to those with PAWP >15 mm Hg. Unclassified-PH had more frequently dilated left atria and higher PAWP than PAH. Although Unclassified-PH had a similar survival to No-PH, 36% were subsequently diagnosed with PAH or PH associated with left heart disease. The presence of 2-3 radiological signs of pulmonary veno-occlusive disease was noted in 7% of PAH patients and was associated with worse survival. Improvement in incremental shuttle walking distance of ≥30 m following initiation of PAH therapy was associated with superior survival. PAH patients diagnosed after 2011 had greater use of combination therapy and superior survival. CONCLUSION: A number of systemic sclerosis PH phenotypes can be recognized and characterized using haemodynamics, lung function and multimodality imaging.
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Hipertensão Pulmonar , Sistema de Registros , Escleroderma Sistêmico , Humanos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/fisiopatologia , Masculino , Feminino , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/diagnóstico , Pessoa de Meia-Idade , Taxa de Sobrevida/tendências , Estudos Retrospectivos , Resistência Vascular/fisiologia , Pressão Propulsora Pulmonar/fisiologia , Adulto , SeguimentosRESUMO
Background: Iron deficiency (ID) is common in patients with pulmonary arterial hypertension and has been associated with increased morbidity and mortality. We aimed to evaluate the therapeutic effects of iron supplementation in iron deficient patients with group 1 to 4 pulmonary hypertension (PH). Methods: A total of 85 PH patients (mean age 69.8 ± 12.0 years, 56.5% female) were included in this prospective trial. Patients were screened for ID at baseline. PH patients with ID received intravenous iron supplementation (500-1000 mg ferric carboxymaltose). PH patients without ID served as control group. At baseline and 16-week follow up, six-minute walk test (6MWT), laboratory testing and echocardiography were performed. Additionally, World Health Organization (WHO) functional class, fatigue score and quality of life (QoL) by the SF-36 questionnaire were assessed. Results: Overall, ID was present in 26.7% (n=8/30), 37.5% (n=9/24), 45.5% (n=10/22) and 44.4% (n=4/9) of patients in PH groups 1-4, respectively. In the total study population, iron restoration led to a significant mitigation of fatigue (p=0.01). However, 6MWT, WHO function class, NT-proBNP levels, QoL and right ventricular function did not change significantly. With regard to the underlying PH group, only PH group 3 patients experienced significant improvements in 6MWT distance (p=0.019), WHO functional class (p=0.017), fatigue (p=0.009) and some QoL domains, as compared to controls. Conclusions: ID was common in PH groups 1 to 4. Though intravenous iron supplementation adequately restored iron status and improved fatigue throughout all patients, in the underlying PH groups treatment was accompanied by improvements in exercise capacity, WHO function class and fatigue only in group 3 PH.
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Hipertensão Pulmonar , Qualidade de Vida , Humanos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Hipertensão Pulmonar/tratamento farmacológico , Estudos Prospectivos , Maltose/análogos & derivados , Maltose/administração & dosagem , Idoso de 80 Anos ou mais , Compostos Férricos/administração & dosagem , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/sangue , Teste de Caminhada , Administração Intravenosa , Resultado do Tratamento , Ferro/administração & dosagem , Ecocardiografia , Suplementos NutricionaisRESUMO
Severe pulmonary vasoconstriction induced by protamine is a rare complication. We report a case of a 77-year-old male patient with a history of mitral valve plasty (MVP). He underwent redo MVP via right thoracotomy under the totally endoscopic procedure (MICS redo-MVP). Immediately after weaning cardiopulmonary bypass (CPB), protamine was administrated. 10 min later peak systolic pulmonary arterial pressure (sys PAP) rose to 62 mmHg, and 30 min later to 80 mmHg. Due to the negative impact of protamine administration, nitric oxide inhalation (iNO) therapy was started with a concentration of 20 ppm. 10 min after iNO therapy started, sys PAP decreased to 63 mmHg. After entering the intensive care unit (ICU), sys PAP decreased to 35 mmHg. Here, we present an effective iNO therapy case for pulmonary hypertension due to protamine and the patient had a good postoperative recovery. This study was approved by the Institutional Review Board at Kitaharima Medical Center (IRB-0602) with the waiver of informed consent.
Assuntos
Hipertensão Pulmonar , Óxido Nítrico , Protaminas , Humanos , Masculino , Idoso , Protaminas/administração & dosagem , Protaminas/uso terapêutico , Óxido Nítrico/administração & dosagem , Administração por Inalação , Antagonistas de Heparina/administração & dosagem , Antagonistas de Heparina/uso terapêutico , Antagonistas de Heparina/efeitos adversos , Endoscopia/métodos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Heparina/administração & dosagem , Heparina/efeitos adversos , Heparina/uso terapêuticoAssuntos
Acetamidas , Pirazinas , Humanos , Acetamidas/uso terapêutico , Pirazinas/uso terapêutico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Hipertensão Pulmonar/tratamento farmacológico , Adulto , Anti-Hipertensivos/uso terapêutico , IdosoRESUMO
OBJECTIVE: This study aims to assess the tricuspid annular plane systolic excursion (TAPSE)/PASP ratio as a potential indicator for predicting the probability of developing pulmonary arterial hypertension (PAH) in hyperthyroidism patients. A nomogram model will be developed based on our findings, as well as the receiver operating characteristic (ROC) curve. METHODS: The study involved 166 hyperthyroid patients treated at Yijishan Hospital, and the period covered August 2021 to August 2022. Patients were divided into two groups according to pulmonary artery systolic pressure ≥35 mmHg. Univariate and multivariate logistic analyses were performed on the two groups' demographic and laboratory data to identify potential diagnostic markers. These parameters were evaluated using ROC curves to determine their precision in forecasting PAH. The findings were validated by plotting a calibration curve based on a line chart model. RESULTS: In the study, eventually, 80 patients were enrolled: 30 in the PAH group and 50 in the No PAH group. Multipleistic regression analysis predicted the occurrence risk of developing PAH. When paired with other conventional echocardiographic parameters (such as TAPSE, MPI, and SV) and serological markers (such as FT3 and FT4), the developed model demonstrated outstanding predictive performance with an area under the ROC curve of 0.985, a Youden index of 0.971, a sensitivity of 100%, and a specificity of 97.1%. CONCLUSIONS: The nomogram model constructed by combining the TAPSE/PASP ratio with FT3 and FT4 serum markers, as well as conventional ultrasound parameters SV and MPI in hyperthyroidism patients, demonstrates robust discriminatory ability and consistency.
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Hipertireoidismo , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , Ecocardiografia/métodos , Adulto , Nomogramas , Valor Preditivo dos Testes , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico , Curva ROC , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/fisiopatologia , Hipertensão Arterial Pulmonar/fisiopatologia , Hipertensão Arterial Pulmonar/complicações , Medição de Risco/métodosRESUMO
BACKGROUND: As one of the most common traffic-related pollutants, diesel exhaust (DE) confers high risk for cardiovascular and respiratory diseases. However, its impact on pulmonary vessels is still unclear. METHODS: To explore the effects of DE exposure on pulmonary vascular remodeling, our study analyzed the number and volume of small pulmonary vessels in the diesel engine testers (the DET group) from Luoyang Diesel Engine Factory and the controls (the non-DET group) from the local water company, using spirometry and carbon content in airway macrophage (CCAM) in sputum. And then we constructed a rat model of chronic DE exposure, in which 12 rats were divided into the DE group (6 rats with 16-week DE exposure) and the control group (6 rats with 16-week clean air exposure). During right heart catheterization, right ventricular systolic pressure (RVSP) was assessed by manometry. Macrophage migration inhibitory factor (MIF) in lung tissues and bronchoalveolar lavage fluid (BALF) were measured by qRT-PCR and ELISA, respectively. Histopathological analysis for cardiovascular remodeling was also performed. RESULTS: In DET cohort, the number and volume of small pulmonary vessels in CT were positively correlated with CCAM in sputum (P<0.05). Rat model revealed that chronic DE-exposed rats had elevated RVSP, along with increased wall thickness of pulmonary small vessels and right the ventricle. What's more, the MIF levels in BALF and lung tissues were higher in DE-exposed rats than the controls. CONCLUSION: Apart from airway remodeling, DE also induces pulmonary vascular remodeling, which will lead to cardiopulmonary dysfunction.
Assuntos
Hipertensão Pulmonar , Ratos Sprague-Dawley , Remodelação Vascular , Emissões de Veículos , Emissões de Veículos/toxicidade , Animais , Remodelação Vascular/fisiologia , Remodelação Vascular/efeitos dos fármacos , Ratos , Masculino , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/efeitos adversos , Adulto , Exposição Ocupacional/efeitos adversos , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Exposição por Inalação/efeitos adversos , FemininoRESUMO
BACKGROUND: Systemic sclerosis (SSc) often overlaps with other autoimmune diseases. More complex autoantibody profiles may be observed in SSc overlap syndrome (SSc OS). To determine the clinical significance of autoantibodies in SSc OS and classify the patients more accurately for better disease assessments, we analysed the correlation between serological profiles, organ involvements and outcomes. METHODS: A retrospective cohort study was conducted in Peking University People's Hospital. Chi-square tests and analysis of variance were used to analyse univariate comparisons of clinical symptoms, organ involvement and laboratory indicators. Survival was evaluated using Cox proportional hazards model. RESULTS: Among 141 cases, anti-Ro-52 was the most common antibody, followed by anti-centromere antibody and anti-Scl-70 antibody. We analysed the correlation between autoantibodies and vital organ damage in SSc OS patients, and compared the differences across four SSc OS subgroups (SSc SLE, SSc RA, SSc PM/DM and SSc SS) to demonstrate the correlation between autoantibodies and clinical characteristics and organ damage. Cox regression analysis showed that scleroderma renal crisis (SRC) (p = .004) and pulmonary arterial hypertension (PH) (p = .010) were independent risk factors for survival. CONCLUSIONS: Autoantibodies are associated with clinical features, organ involvement and prognosis in SSc OS patients. Anti-Scl-70 antibody is associated with interstitial lung disease (ILD) and SRC, while ACA is a protective factor of ILD. SRC and PH are risk factors associated with death.
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Autoanticorpos , Escleroderma Sistêmico , Humanos , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/mortalidade , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/complicações , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Autoanticorpos/sangue , Autoanticorpos/imunologia , Adulto , Modelos de Riscos Proporcionais , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Fatores de Risco , Idoso , Hipertensão Pulmonar/imunologia , Hipertensão Pulmonar/mortalidade , PrognósticoRESUMO
Clinical conditions, including chronic obstructive pulmonary disease or pulmonary arterial hypertension (PAH), can lead to chronic right ventricle pressure overload and progressive right heart failure (RHF). RHF can be identified by right-sided cardiac hypertrophy and dilation associated with abnormal myocardial function affecting the RV and the right atrium (RA). We recently demonstrated that severe RHF is accompanied by an increased risk of atrial inflammation, atrial fibrosis, and atrial fibrillation (AF), the most common type of cardiac arrhythmia (CA). Recent studies have shown that RV and RA inflammation plays an important role in the arrhythmogenesis of CA, including AF. However, the impact of inflammation in the development of CA and AF in RHF is poorly described. Experimental models of RHF are required to better understand the association between right-sided myocardial inflammation and CA. The rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH) is well-established to provoke RHF. However, MCT triggers severe pneumo-toxicity and pulmonary inflammation. Hence, MCT-induced RHF does not help to distinguish whether the subsequent myocardial inflammation originates from the RHF per se or circulating inflammatory signals secreted by the injured lung. In this article, a mechanical method involving pulmonary artery trunk banding (PAB) was used to provoke right-sided cardiac arrhythmogenesis. The PAB consists of performing a permanent suture of the pulmonary artery trunk for 3 weeks. Such an approach generates increased right-sided pressure overload. At D21 post-PAB, the suture results in hypertrophied, dilated, and inflamed RV and RA. The PAB-induced RHF is also accompanied by vulnerability to ventricular and atrial arrhythmias, including AF.