scholarly journals Inflammatory blockade prevents injury to the developing pulmonary gas exchange surface in preterm primates

2021 ◽  
Author(s):  
Andrea Toth ◽  
Shelby Steinmeyer ◽  
Paranthaman Senthamarai Kannan ◽  
Jerilyn Gray ◽  
Courtney Jackson ◽  
...  
Keyword(s):  
Gas Exchange ◽  
Lung Injury ◽  
Structural Integrity ◽  
Close Association ◽  
Capillary Endothelium ◽  
Alveolar Type ◽  
Sequencing Analysis ◽  
Promising Therapeutic Approach ◽  
Increased Risk ◽  
Exchange Surface

Malformations of or injuries to the developing lung are associated with perinatal morbidity and mortality with lifelong consequences for subsequent pulmonary health. One fetal exposure linked with poor health outcomes is chorioamnionitis, which impacts up to 25-40% of preterm births. Severe chorioamnionitis with prematurity is associated with significantly increased risk of pulmonary disease and secondary infections in childhood, suggesting that fetal inflammation may significantly alter developmental ontogeny of the lung. To test this hypothesis, we used intra-amniotic lipopolysaccharide (LPS, endotoxin) to generate experimental chorioamnionitis in prenatal Rhesus macaque (Macaca mulatta), a model which shares critical structural and temporal aspects of human lung development. Inflammatory injury directly disrupts the developing gas exchange surface of the primate lung, with extensive damage to alveolar structure, particularly the close association and coordinated differentiation of alveolar type 1 (AT1) pneumocytes and specialized alveolar capillary endothelium. Single cell RNA sequencing analysis defined a multicellular alveolar signaling niche driving alveologenesis which was extensively disrupted by perinatal inflammation, leading to loss of gas exchange surface, alveolar simplification, and inflammation similar to that found in chronic lung disease of newborns. Blockade of IL1β and TNFα ameliorated endotoxin-induced inflammatory lung injury by blunting stromal response to inflammation and modulating innate immune activation in myeloid cells, restoring structural integrity and key signaling networks in the developing alveolus. These data provide new insight into the pathophysiology of developmental lung injury and suggest that modulating inflammation is a promising therapeutic approach to prevent fetal consequences of chorioamnionitis.

Could Antioxidant Supplementation Delay Progression of Cardiovascular Disease in End-Stage Renal Disease Patients?

2020 ◽  
Vol 19 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Stefanos Roumeliotis ◽  
Athanasios Roumeliotis ◽  
Xenia Gorny ◽  
Peter R. Mertens
Keyword(s):  
Oxidative Stress ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Close Association ◽  
Omega 3 ◽  
Endstage Renal Disease ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
Stage Renal Disease ◽  
End Stage

In end-stage renal disease patients, the leading causes of mortality are of cardiovascular (CV) origin. The underlying mechanisms are complex, given that sudden heart failure is more common than acute myocardial infarction. A contributing role of oxidative stress is postulated, which is increased even at early stages of chronic kidney disease, is gradually augmented in parallel to progression to endstage renal disease and is further accelerated by renal replacement therapy. Oxidative stress ensues when there is an imbalance between reactive pro-oxidants and physiologically occurring electron donating antioxidant defence systems. During the last decade, a close association of oxidative stress with accelerated atherosclerosis and increased risk for CV and all-cause mortality has been established. Lipid peroxidation has been identified as a trigger for endothelial dysfunction, the first step towards atherogenesis. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from studies that test antioxidants for CV protection, such as vitamins E and C, statins, omega-3 fatty acids and N-acetylcysteine.

Diabetes and Heart Failure: Is it Hyperglycemia or Hyperinsulinemia?

2020 ◽  
Vol 18 (2) ◽  
pp. 148-157 ◽  
Author(s):  
Triantafyllos Didangelos ◽  
Konstantinos Kantartzis
Keyword(s):  
Heart Failure ◽  
Insulin Treatment ◽  
Close Association ◽  
Adverse Outcomes ◽  
Negative Effects ◽  
Beneficial Effects ◽  
Appropriate Treatment ◽  
Increased Risk ◽  
Treatment Of Diabetes

The cardiac effects of exogenously administered insulin for the treatment of diabetes (DM) have recently attracted much attention. In particular, it has been questioned whether insulin is the appropriate treatment for patients with type 2 diabetes mellitus and heart failure. While several old and some new studies suggested that insulin treatment has beneficial effects on the heart, recent observational studies indicate associations of insulin treatment with an increased risk of developing or worsening of pre-existing heart failure and higher mortality rates. However, there is actually little evidence that the associations of insulin administration with any adverse outcomes are causal. On the other hand, insulin clearly causes weight gain and may also cause serious episodes of hypoglycemia. Moreover, excess of insulin (hyperinsulinemia), as often seen with the use of injected insulin, seems to predispose to inflammation, hypertension, dyslipidemia, atherosclerosis, heart failure, and arrhythmias. Nevertheless, it should be stressed that most of the data concerning the effects of insulin on cardiac function derive from in vitro studies with isolated animal hearts. Therefore, the relevance of the findings of such studies for humans should be considered with caution. In the present review, we summarize the existing data about the potential positive and negative effects of insulin on the heart and attempt to answer the question whether any adverse effects of insulin or the consequences of hyperglycemia are more important and may provide a better explanation of the close association of DM with heart failure.

scholarly journals Shallow Water Diving-Associated Alveolar Hemorrhage in an Active Duty Sailor: A Case Report

2021 ◽  
Author(s):  
Brannon L Inman ◽  
Rachel E Bridwell ◽  
Amber Cibrario ◽  
Sarah Goss ◽  
Joshua J Oliver
Keyword(s):  
Case Report ◽  
Lung Injury ◽  
Active Duty ◽  
Service Members ◽  
Breath Hold ◽  
Common Complication ◽  
Special Operations ◽  
Increased Risk ◽  
History Of ◽  
And Function

ABSTRACT Breath-hold diving is a common practice as a part of military dive training. An association between prior lung injury and a propensity for lung barotrauma may have the potential to impact mission readiness for combat divers, Pararescue, Combat Controllers, Army Engineer divers, and various units in Naval Special Warfare and Special Operations. Barotrauma is a common complication of diving, typically occurring at depths greater than 30 m (98.4 ft). Individuals with abnormal lung anatomy or function may be at increased risk of barotrauma at shallower depths than those with healthy lungs, rendering these service members unfit for certain missions. We describe the case of a 25-year-old male, with a remote history of polytrauma and resultant pulmonary pleural adhesions, whose dive training was complicated by lung barotrauma at shallow depths. In missions or training utilizing breath-hold diving, the association with secondary alterations in lung or thoracic anatomy and function may limit which service members can safely participate.

scholarly journals Non-Invasive Ventilatory Strategies to Decrease Bronchopulmonary Dysplasia—Where Are We in 2021?

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 132
Author(s):  
Vikramaditya Dumpa ◽  
Vineet Bhandari
Keyword(s):  
Lung Injury ◽  
Bronchopulmonary Dysplasia ◽  
Premature Infants ◽  
Extremely Low Birth Weight ◽  
Positive Pressure ◽  
Invasive Ventilation ◽  
Clinical Practices ◽  
Non Invasive ◽  
Non Invasive Ventilation ◽  
Increased Risk

Recent advances in neonatology have led to the increased survival of extremely low-birth weight infants. However, the incidence of bronchopulmonary dysplasia (BPD) has not improved proportionally, partly due to increased survival of extremely premature infants born at the late-canalicular stage of lung development. Due to minimal surfactant production at this stage, these infants are at risk for severe respiratory distress syndrome, needing prolonged ventilation. While the etiology of BPD is multifactorial with antenatal, postnatal, and genetic factors playing a role, ventilator-induced lung injury is a major, potentially modifiable, risk factor implicated in its causation. Infants with BPD are at a higher risk of developing complications including sepsis, pulmonary arterial hypertension, respiratory failure, and death. Long-term problems include increased risk of hospital readmissions, respiratory infections, and asthma-like symptoms during infancy and childhood. Survivors who have BPD are also at increased risk of poor neurodevelopmental outcomes. While the ultimate solution for avoiding BPD lies in the prevention of preterm births, strategies to decrease its incidence are the need of the hour. It is time to focus on gentler modes of ventilation and the use of less invasive surfactant administration techniques to mitigate lung injury, thereby potentially decreasing the burden of BPD. In this article, we discuss the use of non-invasive ventilation in premature infants, with an emphasis on studies showing an effect on BPD with different modes of non-invasive ventilation. Practical considerations in the use of nasal intermittent positive pressure ventilation are also discussed, considering the significant heterogeneity in clinical practices and management strategies in its use.

Effects of Vaporized Perfluorocarbon on Pulmonary Blood Flow and Ventilation/Perfusion Distribution in a Model of Acute Respiratory Distress Syndrome

2001 ◽  
Vol 95 (6) ◽  
pp. 1414-1421 ◽  
Author(s):  
Matthias Hübler ◽  
Jennifer E. Souders ◽  
Erin D. Shade ◽  
Nayak L. Polissar ◽  
Carmel Schimmel ◽  
...  
Keyword(s):  
Blood Flow ◽  
Oleic Acid ◽  
Gas Exchange ◽  
Lung Injury ◽  
Repeated Measures ◽  
Pulmonary Blood Flow ◽  
Analysis Of Covariance ◽  
Inert Gas ◽  
Low Flow ◽  
Repeated Measures Analysis

Background Perfluorocarbon (PFC) liquids are known to improve gas exchange and pulmonary function in various models of acute respiratory failure. Vaporization has been recently reported as a new method of delivering PFC to the lung. Our aim was to study the effect of PFC vapor on the ventilation/perfusion (VA/Q) matching and relative pulmonary blood flow (Qrel) distribution. Methods In nine sheep, lung injury was induced using oleic acid. Four sheep were treated with vaporized perfluorohexane (PFX) for 30 min, whereas the remaining sheep served as control animals. Vaporization was achieved using a modified isoflurane vaporizer. The animals were studied for 90 min after vaporization. VA/Q distributions were estimated using the multiple inert gas elimination technique. Change in Qrel distribution was assessed using fluorescent-labeled microspheres. Results Treatment with PFX vapor improved oxygenation significantly and led to significantly lower shunt values (P < 0.05, repeated-measures analysis of covariance). Analysis of the multiple inert gas elimination technique data showed that animals treated with PFX vapor demonstrated a higher VA/Q heterogeneity than the control animals (P < 0.05, repeated-measures analysis of covariance). Microsphere data showed a redistribution of Qrel attributable to oleic acid injury. Qrel shifted from areas that were initially high-flow to areas that were initially low-flow, with no difference in redistribution between the groups. After established injury, Qrel was redistributed to the nondependent lung areas in control animals, whereas Qrel distribution did not change in treatment animals. Conclusion In oleic acid lung injury, treatment with PFX vapor improves gas exchange by increasing VA/Q heterogeneity in the whole lung without a significant change in gravitational gradient.

The cell biology and pathogenic role of pulmonary intravascular macrophages

1990 ◽  
Vol 258 (2) ◽  
pp. L1-L12 ◽  
Author(s):  
A. E. Warner ◽  
J. D. Brain
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Cell Biology ◽  
Morphological Characteristics ◽  
Laboratory Animals ◽  
Capillary Endothelium ◽  
Phagocytic Cells ◽  
Pulmonary Uptake ◽  
Pulmonary Intravascular Macrophages

Pulmonary intravascular macrophages (PIMs) are an extensive population of mature phagocytic cells adherent to the pulmonary capillary endothelium in selected species. They are not prevalent in lungs of commonly studied laboratory animals, such as rodents, and thus have only been recently appreciated. However, their potential role in host defense and acute lung injury has attracted interest, since a number of studies have demonstrated pulmonary localization of circulating particles, microbes, and endotoxin by PIMs. Those animal species, such as ruminants, that provide useful models of pathogen (or endotoxin)-induced acute lung injury demonstrate rapid pulmonary uptake of bacteria by PIMs. Inflammatory mediators released by activated PIMs may initiate the process and provoke accumulation of neutrophils and platelets. This review summarizes the morphological characteristics of PIMs and their species distribution. The role of these members of the mononuclear phagocyte system, both beneficial and potentially pathogenic, is reviewed. The question of whether PIMs have a role in acute lung injury in humans is also discussed.

Colloidal gold particles as a new in vivo marker of early acute lung injury

2004 ◽  
Vol 287 (4) ◽  
pp. L867-L878 ◽  
Author(s):  
Kai Heckel ◽  
Rainer Kiefmann ◽  
Martina Dörger ◽  
Mechthild Stoeckelhuber ◽  
Alwin E. Goetz
Keyword(s):  
Electron Microscopy ◽  
Acute Lung Injury ◽  
Gas Exchange ◽  
Lung Injury ◽  
Colloidal Gold ◽  
Microvascular Permeability ◽  
Arterial Oxygen ◽  
Control Group ◽  
Gold Particles

Permeability of the endothelial barrier to large molecules plays a pivotal role in the manifestation of early acute lung injury. We present a novel and sensitive technique that brings microanatomical visualization and quantification of microvascular permeability in line. White New Zealand rabbits were anesthetized and ventilated mechanically. Rabbit serum albumin (RSA) was labeled with colloidal gold particles. We quantified macromolecular leakage of gold-labeled RSA and thickening of the gas exchange distance by electron microscopy, taking into account morphology of microvessels. The control group receiving a saline solution represented a normal gas exchange barrier without extravasation of gold-labeled albumin. Infusion of lipopolysaccharide (LPS) resulted in a significant displacement of gold-labeled albumin into pulmonary cells, the lung interstitium, and even the alveolar space. Correspondingly, intravital fluorescence microscopy and digital image analysis indicated thickening of width of alveolar septa. The findings were accompanied by a deterioration of alveolo-arterial oxygen difference, whereas wet/dry ratio and albumin concentration in the bronchoalveolar lavage fluid failed to detect that early stage of pulmonary edema. Inhibition of the nuclear enzyme poly(ADP-ribose) synthetase by 3-aminobenzamide prevented LPS-induced microvascular injury. To summarize: colloidal gold particles visualized by standard electron microscopy are a new and very sensitive in vivo marker of microvascular permeability in early acute lung injury. This technique enabling detailed microanatomical and quantitative pathophysiological characterization of edema formation can form the basis for evaluating novel treatment strategies against acute lung injury.

scholarly journals Receptor for advanced glycation end-products (RAGE) is an indicator of direct lung injury in models of experimental lung injury

2009 ◽  
Vol 297 (1) ◽  
pp. L1-L5 ◽  
Author(s):  
Xiao Su ◽  
Mark R. Looney ◽  
Naveen Gupta ◽  
Michael A. Matthay
Keyword(s):  
Lung Injury ◽  
Advanced Glycation End Products ◽  
Cell Injury ◽  
Alveolar Epithelial Cell ◽  
Experimental Models ◽  
Alveolar Type ◽  
Type I ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Receptor for advanced glycation end-products (RAGE) is a marker of alveolar type I cells and is elevated in the pulmonary edema fluid of patients with acute lung injury (ALI). We tested the hypothesis that RAGE in the bronchoalveolar lavage (BAL) would be elevated in experimental models of direct ALI characterized by alveolar epithelial cell injury. We developed ELISA measurements for RAGE and studied ALI (direct and indirect) mouse models and collected BAL at specified endpoints to measure RAGE. We also tested whether levels of BAL RAGE correlated 1) with the severity of lung injury in acid and hyperoxia-induced ALI and 2) with the beneficial effect of a novel treatment, mesenchymal stem cells (MSC), in LPS-induced ALI. In ALI models of direct lung injury induced by intratracheal instillation of acid, LPS, or Escherichia coli, the BAL RAGE was 58-, 22-, and 13-fold elevated, respectively. In contrast, BAL RAGE was not detectable in indirect models of ALI induced by an intraperitoneal injection of thiourea or by an intravenous injection of MHC I monoclonal antibody that produces a mouse model of transfusion-related ALI. BAL RAGE did correlate with the severity of lung injury in acid and hyperoxia-induced ALI. In addition, with LPS-induced ALI, BAL RAGE was markedly reduced with MSC treatment. In summary, BAL RAGE is an indicator of ALI, and it may be useful in distinguishing direct from indirect models of ALI as well as assessing the response to specific therapies.

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