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Comprehensive Physiology Mar 2020The pulmonary blood-gas barrier represents a remarkable feat of engineering. It achieves the exquisite thinness needed for gas exchange by diffusion, the strength to... (Review)
Review
The pulmonary blood-gas barrier represents a remarkable feat of engineering. It achieves the exquisite thinness needed for gas exchange by diffusion, the strength to withstand the stresses and strains of repetitive and changing ventilation, and the ability to actively maintain itself under varied demands. Understanding the design principles of this barrier is essential to understanding a variety of lung diseases, and to successfully regenerating or artificially recapitulating the barrier ex vivo. Many classical studies helped to elucidate the unique structure and morphology of the mammalian blood-gas barrier, and ongoing investigations have helped to refine these descriptions and to understand the biological aspects of blood-gas barrier function and regulation. This article reviews the key features of the blood-gas barrier that enable achievement of the necessary design criteria and describes the mechanical environment to which the barrier is exposed. It then focuses on the biological and mechanical components of the barrier that preserve integrity during homeostasis, but which may be compromised in certain pathophysiological states, leading to disease. Finally, this article summarizes recent key advances in efforts to engineer the blood-gas barrier ex vivo, using the platforms of lung-on-a-chip and tissue-engineered whole lungs. © 2020 American Physiological Society. Compr Physiol 10:415-452, 2020.
Topics: Animals; Bioengineering; Blood-Air Barrier; Humans; Lung; Lung Diseases; Pulmonary Circulation; Pulmonary Gas Exchange
PubMed: 32163210
DOI: 10.1002/cphy.c190026 -
Current Opinion in Pulmonary Medicine Sep 2021While there has been a longstanding interest in metabolic disease in pulmonary hypertension, publications in the last several years have translated basic science... (Review)
Review
PURPOSE OF REVIEW
While there has been a longstanding interest in metabolic disease in pulmonary hypertension, publications in the last several years have translated basic science findings to human disease and even led to recently published studies of metabolic therapy in pulmonary arterial hypertension that are discussed here.
RECENT FINDINGS
Progress has been made in four key areas including mechanisms of insulin resistance in pulmonary arterial hypertension, the role of obesity in pulmonary vascular disease, novel clinical trials targeting metabolism in pulmonary hypertension, and the role of metabolism in chronic thromboembolic pulmonary hypertension.
SUMMARY
: Insulin resistance in pulmonary arterial hypertension is primarily in the lipid axis. There are systemic manifestations of insulin resistance including right ventricular lipotoxicity. Obesity is associated with elevation of right ventricular systolic pressure even in a healthy population and therapies in pulmonary arterial hypertension that target metabolism hold promise for improving exercise, right ventricular function, and visceral adiposity. Finally, there are emerging data that chronic thromboembolic pulmonary hypertension is similarly characterized by metabolic alterations, though the specific metabolites may be different from pulmonary arterial hypertension.
Topics: Heart Ventricles; Humans; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Pulmonary Artery; Pulmonary Circulation; Ventricular Function, Right
PubMed: 34127621
DOI: 10.1097/MCP.0000000000000794 -
Open Respiratory Archives 2023The Spanish Society of Pneumology and Thoracic Surgery (SEPAR) has held its 56th congress in Granada from 8 to 10 June 2023. The SEPAR congress has established itself as... (Review)
Review
The Spanish Society of Pneumology and Thoracic Surgery (SEPAR) has held its 56th congress in Granada from 8 to 10 June 2023. The SEPAR congress has established itself as the leading scientific meeting for specialists in medicine and respiratory care, reaching a record of participation this year with 2600 attendees. Our society thus demonstrates its leadership in the management of respiratory diseases, as well as its growth and progress in order to achieve excellence. In this review, we offer a summary of some notable issues addressed in six selected areas of interest: chronic obstructive pulmonary disease (COPD), asthma, interstitial lung diseases (ILDs), tuberculosis and respiratory infections, pulmonary circulation, and respiratory nursing.
PubMed: 37720490
DOI: 10.1016/j.opresp.2023.100265 -
Biomedicines Jan 2024The gut microbiome and its associated metabolites are integral to the maintenance of gut integrity and function. There is increasing evidence that its alteration,... (Review)
Review
The gut microbiome and its associated metabolites are integral to the maintenance of gut integrity and function. There is increasing evidence that its alteration, referred to as dysbiosis, is involved in the development of a systemic conditions such as cardiovascular disease (e.g., systemic hypertension, atherosclerosis). Pulmonary hypertension (PH) is a condition characterised by progressive remodelling and vasoconstriction of the pulmonary circulation, ultimately leading to right ventricular failure and premature mortality if untreated. Initial studies have suggested a possible association between dysbiosis of the microbiome and the development of PH. The aim of this article is to review the current experimental and clinical data with respect to the potential interaction between the gut microbiome and the pathophysiology of pulmonary hypertension. It will also highlight possible new therapeutic targets that may provide future therapies.
PubMed: 38255274
DOI: 10.3390/biomedicines12010169 -
Frontiers in Pharmacology 2023Pulmonary hypertension (PH) is a pathophysiological condition of increased pulmonary circulation vascular resistance due to various reasons, which mainly leads to right... (Review)
Review
Pulmonary hypertension (PH) is a pathophysiological condition of increased pulmonary circulation vascular resistance due to various reasons, which mainly leads to right heart dysfunction and even death, especially in critically ill patients. Although drug interventions have shown some efficacy in improving the hemodynamics of PH patients, the mortality rate remains high. Hence, the identification of new targets and treatment strategies for PH is imperative. Heparanase (HPA) is an enzyme that specifically cleaves the heparan sulfate (HS) side chains in the extracellular matrix, playing critical roles in inflammation and tumorigenesis. Recent studies have indicated a close association between HPA and PH, suggesting HPA as a potential therapeutic target. This review examines the involvement of HPA in PH pathogenesis, including its effects on endothelial cells, inflammation, and coagulation. Furthermore, HPA may serve as a biomarker for diagnosing PH, and the development of HPA inhibitors holds promise as a targeted therapy for PH treatment.
PubMed: 37637421
DOI: 10.3389/fphar.2023.1202676 -
The Journal of Physiology Sep 2023Potassium channel subfamily K member 3 (KCNK3), encoded by the KCNK3 gene, is part of the two-pore domain potassium channel family, constitutively active at resting... (Review)
Review
Potassium channel subfamily K member 3 (KCNK3), encoded by the KCNK3 gene, is part of the two-pore domain potassium channel family, constitutively active at resting membrane potentials in excitable cells, including smooth muscle and cardiac cells. Several physiological and pharmacological mediators, such as intracellular signalling pathways, extracellular pH, hypoxia and anaesthetics, regulate KCNK3 channel function. Recent studies show that modulation of KCNK3 channel expression and function strongly influences pulmonary vascular cell and cardiomyocyte function. The altered activity of KCNK3 in pathological situations such as atrial fibrillation, pulmonary arterial hypertension and right ventricular dysfunction demonstrates the crucial role of KCNK3 in cardiovascular homeostasis. Furthermore, loss of function variants of KCNK3 have been identified in patients suffering from pulmonary arterial hypertension and atrial fibrillation. This review focuses on current knowledge of the role of the KCNK3 channel in pulmonary circulation and the heart, in healthy and pathological conditions.
Topics: Humans; Pulmonary Circulation; Atrial Fibrillation; Pulmonary Arterial Hypertension; Membrane Potentials; Lung; Potassium Channels, Tandem Pore Domain
PubMed: 37477289
DOI: 10.1113/JP284936 -
Medical Hypotheses Oct 2020The current SARS-Cov-2 virus pandemic challenges critical care physicians and other caregivers to find effective treatment for desperately ill patients - especially... (Review)
Review
The current SARS-Cov-2 virus pandemic challenges critical care physicians and other caregivers to find effective treatment for desperately ill patients - especially those with sudden and extreme hypoxemia. Unlike patients with other forms of Acute Respiratory Distress Syndrome, these patients do not exhibit increased lung stiffness or dramatic dyspnea., even in the presence of arterial blood oxygen levels lower than that seen normally in mixed venous blood. Urgent intubation and mechanical ventilation with high inflation pressures and raised inhaled oxygen concentration have proved unhelpful or worse, but why? Our Hypothesis is that sudden opening of a previously undetected probe-patent foramen ovale (PPFO) may explain this mystery. As hypoxemia without acidosis is a rather weak stimulus of dyspnea or increased ventilation, and opening of such an intracardiac shunt would not worsen lung mechanical properties, the absence of dramatic symptom changes would not be surprising. We point out the high frequency of PFO both in life and at autopsy, and the physiological evidence of large shunt fractions found in Covid-19 patients. Published evidence of hypercoagulability and abundant evidence of pulmonary emboli found at autopsy are in accord with our hypothesis, as they would contribute to raised pressure in the pulmonary arteries and right heart chambers, potentially causing a shunt to open. We review the interaction between viral corona spike protein and ACE-2 receptors present on the surface of alveolar lining cells, and contribution to hypercoagulabilty caused by the spike protein. Search for an open PFO after a large drop in arterial oxygen saturation can be performed at the bedside with a variety of well-established techniques including bedside echocardiography, nitrogen washout test, and imaging studies. Potential treatments might include balloon or patch closure of the shunt, and various drug treatments to lower pulmonary vascular resistance.
Topics: Angiotensin-Converting Enzyme 2; Betacoronavirus; COVID-19; Coronavirus Infections; Foramen Ovale, Patent; Humans; Hypoxia; Models, Biological; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Pulmonary Circulation; Receptors, Virus; Respiratory Mechanics; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Thrombophilia
PubMed: 32634734
DOI: 10.1016/j.mehy.2020.110022 -
Indian Journal of Thoracic and... Mar 2020The parallel supply of the pulmonary and systemic circuits complicates the management of single-ventricle lesions. Achieving a balance between the two limbs of the... (Review)
Review
The parallel supply of the pulmonary and systemic circuits complicates the management of single-ventricle lesions. Achieving a balance between the two limbs of the circulation forms the basis of optimizing the systemic oxygen delivery, with the oxygen availability being highly sensitive to alterations in pulmonary/systemic blood flow ratio ( / ). The identification of a 'balanced' circulation is challenging wherein various parameters should be evaluated in close conjunction with each other. The prompt identification of circulatory maldistribution should be backed up with a sound management strategy aimed at attaining an equitable systemic and pulmonary perfusion. Any degree of ventricular dysfunction compromises the total output ( + ) supplying the two circuits explaining the role of inodilators in improving the myocardial performance in addition to lowering the systemic vascular resistance and optimizing / in setting of a single-ventricle physiology. Moreover, the pulmonary circulation is modulated by a multitude of factors intricately linked to the single-ventricle lesion, including anatomical characteristics unique to the underlying lesion (branch pulmonary arterial and venous stenosis), preoperative interventions, associated aortopulmonary and venovenous collaterals, plastic bronchitis, pulmonary arteriovenous fistulae, underlying ventricular dysfunction,, and many others. The article highlights the physiology, diagnosis, therapeutic optimization of a single-ventricle circulation, and the peculiarities pertaining to the pulmonary circulation of the uni-ventricular lesions.
PubMed: 33061117
DOI: 10.1007/s12055-019-00889-w