Pulmonary hypertension: Pathophysiology beyond the lung

Publication date: Available online 13 November 2019Source: Pharmacological ResearchAuthor(s): Aline C. Oliveira, Elaine M. Richards, Mohan K. RaizadaAbstractPulmonary hypertension (PH) is classically considered a disease of pulmonary vasculature which has been the predominant target for drug development and pH therapy. Despite significant advancement in recent years in identification of new drug targets and innovative treatment strategies, the prognosis of pH remains poor, with median survival of 5 years. Recent studies have demonstrated involvement of neuroinflammation, altered autonomic and gastrointestinal functions and increased trafficking of bone marrow-derived cells in cardiopulmonary pathophysiology. This has led to the proposal that pH could be considered a systemic disease involving complex interactions among many organs. Our objectives in this review is to summarize evidence for the involvement of the brain, bone marrow and gut in pH pathophysiology. Then, to synthesize all evidence supporting a brain-gut-lung interaction hypothesis for consideration in pH pathophysiology and finally to summarize unanswered questions and future directions to move this novel concept forward. This forward-thinking view, if proven by further experiments, would provide new opportunities and novel targets for the control and treatment of PH.Graphical abstractIn a novel view of pulmonary hypertension (PH) pathophysiology as a systemic disease, a growing body of evidence indicates that bo...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research

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We present five cases of TBX4 related DPLD/PH who survived beyond infancy with different disease progression. Registry-based follow-up is mandatory to understand genotype-phenotype correlation and improve treatment strategies and prognosis for this rare disease.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Paediatric bronchology Source Type: research
AbstractPurpose of ReviewObstructive sleep apnea (OSA), featured by chronic intermittent hypoxia (CIH), is an independent risk for systemic hypertension (HTN) and is associated with pulmonary hypertension (PH). The precise mechanisms underlying pulmonary vascular remodeling and PH in OSA are not fully understood. However, it has been suggested that lung tissue hypoxia, oxidative stress, and pro-inflammatory mediators following CIH exposure may contribute to PH.Recent FindingsNew evidences obtained in preclinical OSA models support that an enhanced carotid body (CB) chemosensory reactiveness to oxygen elicits sympathetic an...
Source: Current Hypertension Reports - Category: Primary Care Source Type: research
RationalePulmonary hypertension (PH) is a rare but fatal disease characterized by elevated pulmonary pressures and vascular remodeling, leading to right ventricular failure and death. Recently, neuroinflammation has been suggested to be involved in the sympathetic activation in experimental PH. Whether PH is associated with neuroinflammation in the spinal cord has never been investigated.Methods/ResultsPH was well-established in adult male Wistar rats 3-week after pulmonary endothelial toxin Monocrotaline (MCT) injection. Using the thoracic segments of the spinal cord, we found a 5-fold increase for the glial fibrillary ac...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
akasawa Obstructive sleep apnea (OSA) causes many systemic disorders via mechanisms related to sympathetic nerve activation, systemic inflammation, and oxidative stress. OSA typically shows repeated sleep apnea followed by hyperventilation, which results in intermittent hypoxia (IH). IH is associated with an increase in sympathetic activity, which is a well-known pathophysiological mechanism in hypertension and insulin resistance. In this review, we show the basic and clinical significance of IH from the viewpoint of not only systemic regulatory mechanisms focusing on pulmonary circulation, but also cellular mechanisms...
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Review Source Type: research
Cardiac sympathetic blockade with high-thoracic epidural anesthesia is considered beneficial in patients undergoing major surgery because it offers protection in ischemic heart disease. Major outcome studies have failed to confirm such a benefit, however. In fact, there is growing concern about potential harm associated with the use of thoracic epidural anesthesia in high-risk patients, although underlying mechanisms have not been identified. Since the latest review on this subject, a number of clinical and experimental studies have provided new information on the complex interaction between thoracic epidural anesthesia &n...
Source: Anesthesiology - Category: Anesthesiology Source Type: research
Authors: McNicholas WT Abstract Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) syndrome are both highly prevalent, affecting at least 10% of the general adult population, and each has been independently associated with an increased risk of cardiovascular disease. The presence of both disorders together, commonly referred to as the overlap syndrome, is also highly prevalent, although various clinical and pathophysiological factors associated with COPD may increase or decrease the likelihood of OSA. Lung hyperinflation reduces the likelihood of obstructive apnoea, whereas right heart ...
Source: Journal of Thoracic Disease - Category: Respiratory Medicine Tags: J Thorac Dis Source Type: research
Background: Pulmonary arterial hypertension (PAH) is characterized by sympathovagal imbalance, endothelial dysfunction and progressive remodeling of the pulmonary vasculature that results in heart failure and impairs the functional capacity of patients. In this paper, our aim was to establish correlation among the peripheral endothelial function, the sympathovagal modulation and the functional capacity of PAH patients.Methods: PAH patients performed ultrasound of the brachial artery to peripheral endothelial function evaluation and an electrocardiogram for sympathovagal modulation by spectral analysis. The functional capac...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Pulmonary hypertension Source Type: research
Conclusion: Although the peripheral endothelial function did not show significant difference, the IMT improved the sympathovagal balance in these PH patients, probably reducing the cardiovascular risk.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Pulmonary hypertension Source Type: research
Abstract Asphyxiating thoracic dystrophy (ATD also known as Jeune syndrome) is a very rare disorder with an incidence in the United States of 1 case per 100,000-130,000 live births. Chronic alveolar hypoventilation leading to concurrent hypoxia is the main cause of morbidity and mortality in these patients due to its complications. A 22-year-old male with past medical history of ATD and severe kyphoscoliosis presented with progressively worsening shortness of breath for several days. Past surgical history was significant for multiple reconstructive sternal surgeries, his first surgery was at the age of two. His ch...
Source: Respiratory Care - Category: Respiratory Medicine Authors: Tags: Respir Med Case Rep Source Type: research
Publication date: Available online 23 October 2018Source: Respiratory Medicine Case ReportsAuthor(s): Nimeh Najjar, Martin Cerda, Jorge Trabanco, Vinoo Ramsaran, James CuryAbstractAsphyxiating thoracic dystrophy (ATD also known as Jeune syndrome) is a very rare disorder with an incidence in the United States of 1 case per 100,000–130,000 live births. Chronic alveolar hypoventilation leading to concurrent hypoxia is the main cause of morbidity and mortality in these patients due to its complications. A 22-year-old male with past medical history of ATD and severe kyphoscoliosis presented with progressively worsening sh...
Source: Respiratory Medicine Case Reports - Category: Respiratory Medicine Source Type: research
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