RESUMO
PURPOSE: Pulmonary thromboendarterectomy (PTE) is the treatment for patients with chronic thromboembolic disease. In the immediate postoperative period, some patients may still experience life-threatening complications such as reperfusion lung injury, airway bleeding, and persistent pulmonary hypertension with consequent right ventricular dysfunction. These issues may require support with extracorporeal membrane oxygenation (ECMO) as a bridge to recovery or lung transplantation. This study aims to analyze our series of PTEs that require ECMO. METHODS: A descriptive and retrospective analysis of all PTE performed at the Favaloro Foundation University Hospital was conducted between March 2013 and December 2023. RESULTS: A total of 42 patients underwent PTE with a median age of 47 years (interquartile range: 26-76). The incidence of patients with ECMO was 26.6%, of which 53.6% were veno-venous (VV) ECMO. Preoperatively, a low cardiac index (CI), high right and left filling pressures, and high total pulmonary vascular resistances (PVRs) were associated with ECMO with a statistically significant relationship. The hospital mortality was 11.9%, and the mortality in the ECMO group was 45.5%, with a statistically significant relationship. Veno-arterial ECMO has a worse prognosis than VV ECMO. CONCLUSIONS: Preoperatively, a low CI, high right and left filling pressures, and high total PVRs were associated with ECMO after PTE.
Assuntos
Endarterectomia , Oxigenação por Membrana Extracorpórea , Mortalidade Hospitalar , Embolia Pulmonar , Humanos , Oxigenação por Membrana Extracorpórea/mortalidade , Oxigenação por Membrana Extracorpórea/efeitos adversos , Pessoa de Meia-Idade , Endarterectomia/efeitos adversos , Endarterectomia/mortalidade , Masculino , Estudos Retrospectivos , Feminino , Resultado do Tratamento , Adulto , Idoso , Embolia Pulmonar/mortalidade , Embolia Pulmonar/cirurgia , Embolia Pulmonar/fisiopatologia , Fatores de Tempo , Fatores de Risco , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/cirurgia , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/cirurgiaRESUMO
Acute pulmonary embolism (APE) is one of the leading causes of cardiovascular emergencies and the third leading cause of death. Although efforts focus on treating the acute event, patients who survive APE may develop long-term sequelae. Research reveals that approximately half of patients who have suffered an APE do not regain their previous level of function and experience a reduction in their quality of life for several years after the episode. Acute pulmonary embolism can be classified according to the risk of short-term mortality, with most mortality and morbidity concentrated in high-risk and intermediate-risk cases. The first-line treatment for APE is systemic anticoagulation. However, identifying and more aggressively treating people with intermediate to high risk, who have a more favorable risk profile for reperfusion treatments, could reduce short-term mortality and mitigate post-pulmonary embolism syndrome (PPES). Post-pulmonary embolism syndrome refers to a variety of persistent symptoms and functional limitations that occur after an APE. The presence of persistent dyspnea, functional limitations, and/or decreased quality of life after an APE has been recently termed "PPES," although this entity encompasses different manifestations. The most severe cause of persistent dyspnea is chronic thromboembolic pulmonary hypertension, where increased pulmonary artery pressure is due to the fibrotic organization of unresolved APE. Post-PE Syndrome is not always systematically addressed in management guidelines, and its prevalence may be underestimated. More research is needed to fully understand its causes and risk factors. Interventions such as cardiopulmonary rehabilitation have been suggested to improve the quality of life of patients with PPES. A comprehensive, evidence-based approach is essential to effectively prevent and manage PPES and improve the long-term outcomes and well-being of affected patients.
Assuntos
Embolia Pulmonar , Qualidade de Vida , Humanos , Embolia Pulmonar/terapia , Embolia Pulmonar/fisiopatologia , Fatores de Risco , Síndrome , Resultado do Tratamento , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Dispneia/etiologia , Dispneia/fisiopatologia , Medição de Risco , Fatores de Tempo , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/etiologia , Estado FuncionalRESUMO
Although Down syndrome (DS) is considered a risk factor for hemodynamic instabilities (mainly pulmonary hypertension-PH) following surgery for congenital cardiac communications, many DS patients do surprising well postoperatively. We prospectively analyzed perioperative factors for a possible correlation with post-cardiopulmonary bypass (CPB) inflammatory reaction and postoperative PH in pediatric subjects. Sixty patients were enrolled (age 3 to 35 months), 39 of them with DS. Clinical and echocardiographic parameters (anatomical and hemodynamic) were computed preoperatively. Pulmonary and systemic mean arterial pressures (PAP and SAP) were assessed invasively intra and postoperatively. Immediate postoperative PAP/SAP ratio (PAP/SAPIPO) and the behavior of pressure curves were selected as primary outcome. Serum levels of 36 inflammatory proteins were measured by chemiluminescence preoperatively and 4 h post CPB. Of all factors analyzed, peripheral oxygen saturation (O2Sat, bedside assessment) was the only preoperative predictor of PAP/SAPIPO at multivariate analysis (p = 0.007). Respective values in non-DS, DS/O2Sat ≥ 95% and DS/O2Sat < 95% subgroups were 0.34 (0.017), 0.40 (0.027) and 0.45 (0.026), mean (SE), p = 0.004. The difference between non-DS and DS groups regarding postoperative PAP curves (upward shift in DS patients, p = 0.015) became nonsignificant (p = 0.114) after adjustment for preoperative O2Sat. Post-CPB levels of at least 5 cytokines were higher in patients with O2Sat < 95% versus those at or above this level, even within the DS group (p < 0.05). Thus, a baseline O2Sat < 95% representing pathophysiological phenomena in the airways and the distal lung, rather than DS in a broad sense, seems to be associated with post-CPB inflammation and postoperative PH in these patients.
Assuntos
Síndrome de Down , Cardiopatias Congênitas , Hemodinâmica , Humanos , Feminino , Masculino , Lactente , Síndrome de Down/fisiopatologia , Pré-Escolar , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/fisiopatologia , Período Pós-Operatório , Estudos Prospectivos , Ponte Cardiopulmonar/efeitos adversos , Complicações Pós-Operatórias/etiologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Fatores de RiscoRESUMO
BACKGROUND: Adverse remodeling of lung vessels elevates pulmonary pressure and provokes pulmonary arterial hypertension (PAH). PAH results in increased right ventricle (RV) afterload, causing ventricular hypertrophy and the onset of heart failure. There is no specific treatment for maladaptive RV remodeling secondary to PAH. OBJECTIVES: This study aims to explore two therapeutic approaches, grape juice (GJ) and thyroid hormones (TH), on PAH-induced oxidative stress and cardiac functional changes. METHODS: Parameters of echocardiography related to lung vessel resistance (AT/ET ratio), RV contractility (TAPSE), and RV diastolic function (E/A peaks ratio) were evaluated. Also, total ROS, lipid peroxidation, antioxidant enzymes, calcium handling proteins, pro-oxidant and antioxidant protein expression were measured. Values of p<0.05 were considered statistically significant. RESULTS: Both GJ and TH treatments demonstrated reductions in pulmonary resistance (~22%) and improvements in TAPSE (inotropism ~11%) and AT/ET ratio (~26%) (p<0.05). There were no changes amongst groups regarding the E/A peak ratio. Although ROS and TBARS were not statistically significant, GJ and TH treatments decreased xanthine oxidase (~49%) levels and normalized HSP70 and calcium handling protein expression (p<0.05). However, only TH treatment ameliorated diastolic function (~50%) and augmented NRF2 immunocontent (~48%) (p<0.05). CONCLUSIONS: To the best of our knowledge, this study stands as a pioneer in showing that TH administered together with GJ promoted functional and biochemical improvements in a PAH model. Moreover, our data suggest that GJ and TH treatments were cardioprotective, combined or not, and exhibited their beneficial effects by modulating oxidative stress and calcium-handling proteins.
FUNDAMENTO: A remodelação adversa dos vasos pulmonares eleva a pressão pulmonar e provoca hipertensão arterial pulmonar (HAP). A HAP resulta em aumento da pós-carga do ventrículo direito (VD), causando hipertrofia ventricular e consequente insuficiência cardíaca. Não existe um tratamento específico para o remodelamento desadaptativo do VD secundário à HAP. OBJETIVOS: Este estudo tem como objetivo explorar duas abordagens terapêuticas, o suco de uva (SU) e os hormônios tireoidianos (HT), no tratamento do estresse oxidativo induzido pela HAP e nas alterações funcionais cardíacas. MÉTODOS: Parâmetros ecocardiográficos relacionados à resistência dos vasos pulmonares (relação TA/TE), contratilidade do VD (ESPAT) e função diastólica do VD (relação dos picos E/A) foram avaliados. Além disso, foram medidos ROS totais, peroxidação lipídica, enzimas antioxidantes, proteínas de manipulação de cálcio, expressão de proteínas pró-oxidantes e antioxidantes. Valores de p<0,05 foram considerados estatisticamente significativos. RESULTADOS: Ambos os tratamentos, com SU e HT, demonstraram uma redução na resistência pulmonar (~22%), além de melhorias na ESPAT (inotropismo ~11%) e na relação TA/TE (~26%) (p<0,05). Não houve alterações entre os grupos na relação do pico de E/A. Embora ROS e TBARS não tenham sido estatisticamente significativos, os tratamentos com SU e HT diminuíram os níveis de xantina oxidase (~49%) e normalizaram a expressão de HSP70 e proteínas de manipulação de cálcio (p<0,05). No entanto, apenas o tratamento com HT melhorou a função diastólica (~50%) e aumentou o imunoconteúdo de NRF2 (~48%) (p<0,05). CONCLUSÕES: Até onde sabemos, este estudo é pioneiro ao mostrar que o HT administrado em conjunto com o SU promoveu melhorias funcionais e bioquímicas em um modelo de HAP. Além disso, nossos dados sugerem que os tratamentos com SU e HT se mostraram cardioprotetores, sejam combinados ou não, e exibiram seus benefícios ao modular o estresse oxidativo e as proteínas de manipulação do cálcio.
Assuntos
Modelos Animais de Doenças , Sucos de Frutas e Vegetais , Hipertensão Pulmonar , Estresse Oxidativo , Hormônios Tireóideos , Função Ventricular Direita , Vitis , Estresse Oxidativo/efeitos dos fármacos , Vitis/química , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Animais , Masculino , Função Ventricular Direita/efeitos dos fármacos , Função Ventricular Direita/fisiologia , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Ecocardiografia , Antioxidantes/administração & dosagem , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/fisiologia , Peroxidação de Lipídeos/efeitos dos fármacosRESUMO
Pulmonary arterial hypertension (PAH) is characterized by right ventricular failure and diminished cardiac output, potentially leading to renal and bone impairments. In contrast, resistance exercise training (RT) offers cardiovascular and bone health benefits. This study aimed to assess the impacts of stable PAH induced by monocrotaline (MCT) and RT on renal morphometry, as well as bone morphometry and biomechanical properties in male Wistar rats. Four experimental groups, untrained control (UC, n=7), trained control (TC, n=7), untrained hypertensive (UH, n=7), trained hypertensive (TH, n=7), were defined. After the first MCT or saline injection (20 mg/kg), trained rats were submitted to a RT program (i.e., Ladder climbing), 5 times/week. Seven days later the rats received the second MCT or saline dose. After euthanasia, renal and femoral histomorphometry and femoral biomechanical properties were assessed. PAH reduced renal glomerular area and volume, which was prevented by the RT. While PAH did not harm the femoral morphometry, structural and mechanical properties, RT improved the femoral parameters (e.g., length, percentage of trabeculae and bone marrow, ultimte and yield loads). Experimental stable PAH promotes renal but not bone damages, whereas RT prevents renal deteriorations and improves the femoral morphological and biomechanical properties.
Assuntos
Modelos Animais de Doenças , Rim , Monocrotalina , Condicionamento Físico Animal , Ratos Wistar , Treinamento Resistido , Animais , Masculino , Condicionamento Físico Animal/fisiologia , Ratos , Rim/fisiopatologia , Rim/patologia , Treinamento Resistido/métodos , Hipertensão Arterial Pulmonar/fisiopatologia , Fêmur/patologia , Fêmur/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/induzido quimicamenteRESUMO
Introducción: Los leiomiomas uterinos son un tipo de neoplasia benigna de frecuente aparición en mujeres de edad reproductiva, relacionados con enfermedad tromboem- bólica venosa. Este vínculo surge del efecto producido por la compresión de fibromas que genera estasis venosa en la región pelviana. Sin embargo, este pareciera no ser el único factor que lo relaciona con el desarrollo posterior de hipertensión pulmonar, sino que su presencia es gatillo de una serie de fenómenos que influyen sobre la vasculatu - ra pulmonar y también a nivel sistémico. Método: Revisión de una serie de casos (seis) atendidos en nuestra unidad, seguido de una revisión sobre la relación entre leiomio- mas y distintas formas de hipertensión pulmonar con una revisión desde la fisiopatología. Resultado y conclusiones: Encontramos sustento bibliográfico en los múltiples caminos fisiopatológicos que relacionan los mediadores vasculares comunes, que parecieran ser el punto clave en la relación entre estas dos patologías.
Introduction: Uterine leiomyomas are a type of benign neoplasm that frequently appears in women of reproductive age, related to venous thromboembolic disease. This link arises from the effect produced by the compression of fibroids, which generates venous stasis in the pelvic region. However, this seems not to be the only factor that re- lates it to the subsequent development of pulmonary hypertension, but rather its presence is a trigger for a series of phenomena that influence the pulmonary vasculature and also at a systemic level. Method: Review of a series of cases (six) cared for in our unit, followed by a review on the relationship between leiomyomas and different forms of pulmonary hypertension with a review from the pathophysiology. Result and conclusions: We found bibliographic support in the multiple pathophysiological paths that relate the common vascular mediators, which appear to be the key point in the relationship between these two pathologies.
Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias Uterinas/fisiopatologia , Tromboembolia Venosa/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Leiomioma/fisiopatologia , Ecocardiografia , Cateterismo Cardíaco/métodos , Biomarcadores , Revisão , Angiografia por Tomografia Computadorizada/métodosRESUMO
ABSTRACT: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance (PVR), imposing overload on the right ventricle (RV) and imbalance of the redox state. Our study investigated the influence of treatment with sulforaphane (SFN), found in cruciferous vegetables, on RV remodeling and redox homeostasis in monocrotaline (MCT)-induced PAH. Male Wistar rats were separated into 4 groups: control (CTR); CTR + SFN; MCT; and MCT + SFN. PAH induction was implemented by a single dose of MCT (60 mg/kg intraperitoneally). Treatment with SFN (2.5 mg/kg/day intraperitoneally) started on the seventh day after the MCT injection and persisted for 2 weeks. After 21 days of PAH induction, echocardiographic, hemodynamic, and oxidative stress evaluation was performed. The MCT group showed an increase in RV hypertrophy, RV systolic area, RV systolic, mean pulmonary artery pressure, and PVR and exhibited a decrease in the RV outflow tract acceleration time/ejection time ratio, RV fractional shortening, and tricuspid annular plane systolic excursion compared to CTR ( P < 0.05). SFN-treated PAH attenuated detrimental changes in tricuspid annular plane systolic excursion, mean pulmonary artery pressure, and PVR parameters. Catalase levels and the glutathione/Glutathione disulfide (GSSG) ratio were diminished in the MCT group compared to CTR ( P < 0.05). SFN increased catalase levels and normalized the glutathione/GSSG ratio to control levels ( P < 0.05). Data express the benefit of SFN treatment on the cardiac function of rats with PAH associated with the cellular redox state.
Assuntos
Modelos Animais de Doenças , Isotiocianatos , Monocrotalina , Oxirredução , Estresse Oxidativo , Ratos Wistar , Sulfóxidos , Função Ventricular Direita , Animais , Sulfóxidos/farmacologia , Isotiocianatos/farmacologia , Masculino , Função Ventricular Direita/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Hipertrofia Ventricular Direita/fisiopatologia , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/tratamento farmacológico , Homeostase/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/induzido quimicamente , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/metabolismo , Ratos , Pressão Arterial/efeitos dos fármacos , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/fisiopatologia , Hipertensão Arterial Pulmonar/metabolismo , Disfunção Ventricular Direita/fisiopatologia , Disfunção Ventricular Direita/tratamento farmacológico , Disfunção Ventricular Direita/metabolismoRESUMO
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by an imbalance between vasoactive mediators, which causes vascular remodeling, increased pulmonary vascular resistance, and right ventricular overload, ultimately leading to heart failure and death. A metabolic theory has been suggested to explain the pathophysiology of PAH whereby abnormalities in mitochondrial biogenesis can trigger a hyperproliferative and apoptosis-resistant phenotype in cardiopulmonary and malignant cells, leading to mitochondrial dysfunction, which in turn causes the Warburg effect. This can culminate in the mitophagy of pulmonary vessels and cardiomyocytes. The present narrative review focuses on the pathophysiology of PAH, the pharmacological agents currently available for its treatment, and promising and challenging areas of therapeutic investigation.
Assuntos
Anti-Hipertensivos , Hipertensão Arterial Pulmonar , Artéria Pulmonar , Humanos , Animais , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/fisiopatologia , Hipertensão Arterial Pulmonar/metabolismo , Transdução de Sinais/efeitos dos fármacos , Pressão Arterial/efeitos dos fármacos , Resultado do Tratamento , Remodelação Vascular/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologiaRESUMO
La hipertensión arterial pulmonar se caracteriza por una presión arterial pulmonar media y resistencia vascular pulmonar elevadas y remodelado patológico de las arterias pulmonares. La entrada de calcio desde el espacio extracelular al intracelular a través de canales dependientes e independientes de voltaje juega un rol fundamental en el aumento de la contractilidad de las arterias pulmonares y la pérdida de regulación del comportamiento proliferativo de las células de las distintas capas de la pared de las arterias pulmonares. De esta manera, estos canales contribuyen con la vasoconstricción exacerbada de las arterias pulmonares y a su remodelado patológico. El objetivo de esta revisión es recapitular la evidencia obtenida desde modelos celulares y animales respecto a la contribución de los principales canales de calcio de membrana plasmática en estos mecanismos fisiopatológicos claves en el desarrollo de la hipertensión pulmonar, discutiendo su valor potencial como diana farmacológica para terapias presentes y futuras.
Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium entry from the extracellular to the intracellular space through voltage-dependent and -independent channels play a major role in the increase of contractility of pulmonary arteries and in the loss of regulation of the proliferative behavior of the cells from the different layers of the pulmonary arterial wall. In doing so, these channels contribute to enhanced vasoconstriction of pulmonary arteries and their pathological remodeling. This review aims to summarize the evidence obtained from animal and cellular models regarding the involvement of the main plasma membrane calcium channels in these key pathophysiological processes for pulmonary arterial hypertension, discussing the potential value as pharmacological targets for therapies in the present and the future.