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Journal of Perinatology : Official... Oct 2023Meconium aspiration syndrome (MAS) is a complex respiratory disease that continues to be associated with significant morbidities and mortality. The pathophysiological... (Review)
Review
Meconium aspiration syndrome (MAS) is a complex respiratory disease that continues to be associated with significant morbidities and mortality. The pathophysiological mechanisms of MAS include airway obstruction, local and systemic inflammation, surfactant inactivation and persistent pulmonary hypertension of the newborn (PPHN). Supplemental oxygen and non-invasive respiratory support are the main therapies for many patients. The management of the patients requiring invasive mechanical ventilation could be challenging because of the combination of atelectasis and air trapping. While studies have explored various ventilatory modalities, evidence to date does not clearly support any singular modality as superior. Patient's pathophysiology, symptom severity, and clinician/unit expertise should guide the respiratory management. Early identification and concomitant management of PPHN is critically important as it contributes significantly to mortality and morbidities.
Topics: Female; Humans; Infant, Newborn; Meconium Aspiration Syndrome; Respiration, Artificial; Persistent Fetal Circulation Syndrome; Pulmonary Surfactants; Morbidity
PubMed: 37543651
DOI: 10.1038/s41372-023-01708-2 -
Physiological Reviews Jul 2023The pulmonary circulation is a low-resistance, low-pressure, and high-compliance system that allows the lungs to receive the entire cardiac output. Pulmonary arterial... (Review)
Review
The pulmonary circulation is a low-resistance, low-pressure, and high-compliance system that allows the lungs to receive the entire cardiac output. Pulmonary arterial pressure is a function of cardiac output and pulmonary vascular resistance, and pulmonary vascular resistance is inversely proportional to the fourth power of the intraluminal radius of the pulmonary artery. Therefore, a very small decrease of the pulmonary vascular lumen diameter results in a significant increase in pulmonary vascular resistance and pulmonary arterial pressure. Pulmonary arterial hypertension is a fatal and progressive disease with poor prognosis. Regardless of the initial pathogenic triggers, sustained pulmonary vasoconstriction, concentric vascular remodeling, occlusive intimal lesions, in situ thrombosis, and vascular wall stiffening are the major and direct causes for elevated pulmonary vascular resistance in patients with pulmonary arterial hypertension and other forms of precapillary pulmonary hypertension. In this review, we aim to discuss the basic principles and physiological mechanisms involved in the regulation of lung vascular hemodynamics and pulmonary vascular function, the changes in the pulmonary vasculature that contribute to the increased vascular resistance and arterial pressure, and the pathogenic mechanisms involved in the development and progression of pulmonary hypertension. We focus on reviewing the pathogenic roles of membrane receptors, ion channels, and intracellular Ca signaling in pulmonary vascular smooth muscle cells in the development and progression of pulmonary hypertension.
Topics: Humans; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Ion Channels; Lung; Vasoconstriction; Calcium Signaling; Myocytes, Smooth Muscle
PubMed: 36422993
DOI: 10.1152/physrev.00030.2021 -
International Journal of Nanomedicine 2023Exosomes are small extracellular vesicles, ranging in size from 30-150nm, which can be derived from various types of cells. In recent years, mammalian-derived exosomes... (Review)
Review
Exosomes are small extracellular vesicles, ranging in size from 30-150nm, which can be derived from various types of cells. In recent years, mammalian-derived exosomes have been extensively studied and found to play a crucial role in regulating intercellular communication, thereby influencing the development and progression of numerous diseases. Traditional Chinese medicine has employed plant-based remedies for thousands of years, and an increasing body of evidence suggests that plant-derived exosome-like nanovesicles (PELNs) share similarities with mammalian-derived exosomes in terms of their structure and function. In this review, we provide an overview of recent advances in the study of PELNs and their potential implications for human health. Specifically, we summarize the roles of PELNs in respiratory, digestive, circulatory, and other diseases. Furthermore, we have extensively investigated the potential shortcomings and challenges in current research regarding the mechanism of action, safety, administration routes, isolation and extraction methods, characterization and identification techniques, as well as drug-loading capabilities. Based on these considerations, we propose recommendations for future research directions. Overall, our review highlights the potential of PELNs as a promising area of research, with broad implications for the treatment of human diseases. We anticipate continued interest in this area and hope that our summary of recent findings will stimulate further exploration into the implications of PELNs for human health.
Topics: Humans; Animals; Exosomes; Extracellular Vesicles; Cell Communication; Medicine, Chinese Traditional; Pulmonary Circulation; Mammals
PubMed: 37693885
DOI: 10.2147/IJN.S420748 -
Current Opinion in Critical Care Feb 2024Positive end-expiratory pressure (PEEP) is required in the Berlin definition of acute respiratory distress syndrome and is a cornerstone of its treatment. Application of... (Review)
Review
PURPOSE OF REVIEW
Positive end-expiratory pressure (PEEP) is required in the Berlin definition of acute respiratory distress syndrome and is a cornerstone of its treatment. Application of PEEP increases airway pressure and modifies pleural and transpulmonary pressures according to respiratory mechanics, resulting in blood volume alteration into the pulmonary circulation. This can in turn affect right ventricular preload, afterload and function. At the opposite, PEEP may improve left ventricular function, providing no deleterious effect occurs on the right ventricle.
RECENT FINDINGS
This review examines the impact of PEEP on cardiac function with regards to heart-lung interactions, and describes its consequences on organs perfusion and function, including the kidney, gut, liver and the brain. PEEP in itself is not beneficious nor detrimental on end-organ hemodynamics, but its hemodynamic effects vary according to both respiratory mechanics and association with other hemodynamic variables such as central venous or mean arterial pressure. There are parallels in the means of preventing deleterious impact of PEEP on the lungs, heart, kidney, liver and central nervous system.
SUMMARY
The quest for optimal PEEP settings has been a prominent goal in ARDS research for the last decades. Intensive care physician must maintain a high degree of vigilance towards hemodynamic effects of PEEP on cardiac function and end-organs circulation.
Topics: Humans; Positive-Pressure Respiration; Hemodynamics; Lung; Respiratory Mechanics; Respiratory Distress Syndrome
PubMed: 38085886
DOI: 10.1097/MCC.0000000000001124 -
Journal of the American College of... Aug 2023Limited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and... (Clinical Trial)
Clinical Trial
BACKGROUND
Limited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and preserved left ventricular ejection fraction (HFpEF).
OBJECTIVES
This study sought to assess the clinical implications of RV function, the association with N-terminal pro-B-type natriuretic peptide, and the risk for adverse events among patients with HFpEF.
METHODS
This study analyzed measures of RV function by assessing absolute RV free wall longitudinal strain (RVFWLS) and its ratio to estimated pulmonary artery systolic pressure (PASP) (RVFWLS/PASP ratio) in 528 patients (mean age 74 ± 8 years, 56% female) with adequate echocardiographic images quality enrolled in the PARAGON-HF trial. Associations with baseline N-terminal pro-B-type natriuretic peptide and with total HF hospitalizations and cardiovascular death were assessed, after accounting for confounders.
RESULTS
Overall, 311 patients (58%) had evidence of RV dysfunction, defined as absolute RVFWLS <20%, and among the 388 patients (73%) with normal tricuspid annular planar systolic excursion and RV fractional area change, more than one-half showed impaired RV function. Lower values of RVFWLS and RVFWLS/PASP ratios were significantly associated with higher circulating N-terminal pro-B-type natriuretic peptide. With a median follow-up of 2.8 years, there were 277 total HF hospitalizations and cardiovascular deaths. Both absolute RVFWLS (HR: 1.39; 95% CI: 1.05-1.83; P = 0.018) and RVFWLS/PASP ratio (HR: 1.43; 95% CI: 1.13-1.80; P = 0.002) were significantly associated with the composite outcome. Treatment effect of sacubitril/valsartan was not modified by measures of RV function.
CONCLUSIONS
Worsening RV function and its ratio to pulmonary pressure is common and significantly associated with an increased risk of HF hospitalizations and cardiovascular death in patients with HFpEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Heart Failure; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right
PubMed: 37225045
DOI: 10.1016/j.jacc.2023.05.010 -
Presse Medicale (Paris, France : 1983) Sep 2023Pulmonary arterial hypertension (PAH) is a rare and progressive disease characterised by remodelling of the pulmonary arteries and progressive narrowing of the pulmonary... (Review)
Review
Pulmonary arterial hypertension (PAH) is a rare and progressive disease characterised by remodelling of the pulmonary arteries and progressive narrowing of the pulmonary vasculature. This leads to a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure and, if left untreated, to right ventricular failure and death. A correct diagnosis requires a complete work-up including right heart catheterisation performed in a specialised centre. Although our knowledge of the epidemiology, pathology and pathophysiology of the disease, as well as the development of innovative therapies, has progressed in recent decades, PAH remains a serious clinical condition. Current treatments for the disease target the three specific pathways of endothelial dysfunction that characterise PAH: the endothelin, nitric oxide and prostacyclin pathways. The current treatment algorithm is based on the assessment of severity using a multiparametric risk stratification approach at the time of diagnosis (baseline) and at regular follow-up visits. It recommends the initiation of combination therapy in PAH patients without cardiopulmonary comorbidities. The choice of therapy (dual or triple) depends on the initial severity of the condition. The main treatment goal is to achieve low-risk status. Further escalation of treatment is required if low-risk status is not achieved at subsequent follow-up assessments. In the most severe patients, who are already on maximal medical therapy, lung transplantation may be indicated. Recent advances in understanding the pathophysiology of the disease have led to the development of promising emerging therapies targeting dysfunctional pathways beyond endothelial dysfunction, including the TGF-β and PDGF pathways.
Topics: Humans; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Lung Transplantation; Antihypertensive Agents
PubMed: 37516248
DOI: 10.1016/j.lpm.2023.104168