Distinct effects of intravenous bone marrow-derived mesenchymal stem cell therapy on ischemic and non-ischemic lungs after ischemia-reperfusion injury.

Background: The preclinical efficacy of mesenchymal stem cell (MSC) therapy after intravenous infusion has been promising, but clinical studies have yielded only modest results. Although most preclinical studies have focused solely on the ischemic lung, it is crucial to evaluate both lungs after ischemia-reperfusion injury, considering the various mechanisms involved. This study aimed to bridge this gap by assessing the acute effects of bone marrow MSC(BM) infusion before ischemic insult and evaluating both ischemic and non-ischemic lungs after reperfusion.

Therapeutic effects of hypoxia-preconditioned bone marrow-derived mesenchymal stromal cells and their extracellular vesicles in experimental pulmonary arterial hypertension.

Aims: To evaluate BM-MSCs and their extracellular vesicles (EVs) preconditioned with hypoxia or normoxia in experimental pulmonary arterial hypertension (PAH).

Main Methods: BM-MSCs were isolated and cultured under normoxia (MSC-N, 21%O) or hypoxia (MSC-H, 1%O) for 48 h. EVs were then isolated from MSCs under normoxia (EV-N) or hypoxia (EV-H).

Lung Injury Is Induced by Abrupt Increase in Respiratory Rate but Prevented by Recruitment Maneuver in Mild Acute Respiratory Distress Syndrome in Rats.

Background: Gradually changing respiratory rate (RR) during time to reduce ventilation-induced lung injury has not been investigated. The authors hypothesized that gradual, compared with abrupt, increments in RR would mitigate ventilation-induced lung injury and that recruitment maneuver before abruptly increasing RR may prevent injurious biologic impact.

Methods: Twenty-four hours after intratracheal administration of Escherichia coli lipopolysaccharide, 49 male Wistar rats were anesthetized and mechanically ventilated (tidal volume, 6 ml/kg; positive end-expiratory pressure, 3 cm H2O) with RR increase patterns as follows (n = 7 per group): (1) control 1, RR = 70 breaths/min for 2 h; (2) and (3) abrupt increases of RR for 1 and 2 h, respectively, both for 2 h; (4) shorter RR adaptation, gradually increasing RR (from 70 to 130 breaths/min during 30 min); (5) longer RR adaptation, more gradual increase in RR (from 70 to 130 breaths/min during 60 min), both for 2 h; (6) control 2, abrupt increase of RR maintained for 1 h; and (7) control 3, recruitment maneuver (continuous positive airway pressure, 30 cm H2O for 30 s) followed by control-2 protocol.

Mild hypothermia combined with dexmedetomidine reduced brain, lung, and kidney damage in experimental acute focal ischemic stroke.

Background: Sedatives and mild hypothermia alone may yield neuroprotective effects in acute ischemic stroke (AIS). However, the impact of this combination is still under investigation. We compared the effects of the combination of mild hypothermia or normothermia with propofol or dexmedetomidine on brain, lung, and kidney in experimental AIS.

Biological impact of restrictive and liberal fluid strategies at low and high PEEP levels on lung and distal organs in experimental acute respiratory distress syndrome.

Fluid regimens in acute respiratory distress syndrome (ARDS) are conflicting. The amount of fluid and positive end-expiratory pressure (PEEP) level may interact leading to ventilator-induced lung injury (VILI). We therefore evaluated restrictive and liberal fluid strategies associated with low and high PEEP levels with regard to lung and kidney damage, as well as cardiorespiratory function in endotoxin-induced ARDS.

Effects of different fluid management on lung and kidney during pressure-controlled and pressure-support ventilation in experimental acute lung injury.

Optimal fluid management is critical during mechanical ventilation to mitigate lung damage. Under normovolemia and protective ventilation, pulmonary tensile stress during pressure-support ventilation (PSV) results in comparable lung protection to compressive stress during pressure-controlled ventilation (PCV) in experimental acute lung injury (ALI). It is not yet known whether tensile stress can lead to comparable protection to compressive stress in ALI under a liberal fluid strategy (LF).

Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Nitazoxanide exerts antiviral activity and and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain.

Methods: A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled.

A more gradual positive end-expiratory pressure increase reduces lung damage and improves cardiac function in experimental acute respiratory distress syndrome.

Increases in positive end-expiratory pressure (PEEP) or recruitment maneuvers may increase stress in lung parenchyma, extracellular matrix, and lung vessels; however, adaptative responses may occur. We evaluated the effects of PEEP on lung damage and cardiac function when increased abruptly, gradually, or more gradually in experimental mild/moderate acute respiratory distress syndrome (ARDS) induced by lipopolysaccharide intratracheally. After 24 h, Wistar rats ( = 48) were randomly assigned to four mechanical ventilation strategies according to PEEP levels: ) 3 cmHO for 2 h (control); ) 3 cmHO for 1 h followed by an abrupt increase to 9 cmHO for 1 h (no adaptation time); ) 3 cmHO for 30 min followed by a gradual increase to 9 cmHO over 30 min then kept constant for 1 h (shorter adaptation time); and 4) more gradual increase in PEEP from 3 cmHO to 9 cmHO over 1 h and kept constant thereafter (longer adaptation time).

Niclosamide attenuates lung vascular remodeling in experimental pulmonary arterial hypertension.

Despite advances in medical therapy, pulmonary arterial hypertension (PAH) remains an inexorably progressive and highly lethal disease. Signal transducer and activator of transcription (STAT)-3 is one of the main intracellular transcription factors implicated in PAH vascular remodeling. We hypothesized that niclosamide, a STAT3 inhibitor, would reduce vascular remodeling in an established pulmonary arterial hypertension model, thus enhancing cardiac function.

Pros and cons of corticosteroid therapy for COVID-19 patients.

In December 2019, an outbreak of severe pneumonia was reported in Wuhan, China. Later described as COVID-19 (coronavirus disease 2019), this infection caused by a virus from the Coronaviridae family (SARS-CoV-2) has spread globally. Effective therapies for this new disease are urgently needed.

Effects of the FGF receptor-1 inhibitor, infigratinib, with or without sildenafil, in experimental pulmonary arterial hypertension.

Background And Purpose: Pulmonary arterial hypertension (PAH) is a progressive disease associated with high morbidity and mortality, despite advances in medical therapy. We compared the effects of infigratinib (NVP-BGJ398), a new FGF receptor-1 inhibitor, with or without the PDE-5 inhibitor sildenafil, on vascular function and remodelling as well as on gene expression of signal transducers for receptors of TGF-β (Smads-1/2/4) and transcription factor of endothelial-mesenchymal transition (Twist-1) in established experimental PAH. Types I and III pro-collagen and TGF-β expressions in lung fibroblasts were analysed in vitro after the different treatments.

Gradually Increasing Tidal Volume May Mitigate Experimental Lung Injury in Rats.

Background: This study hypothesized that, in experimental mild acute respiratory distress syndrome, lung damage caused by high tidal volume (VT) could be attenuated if VT increased slowly enough to progressively reduce mechanical heterogeneity and to allow the epithelial and endothelial cells, as well as the extracellular matrix of the lung to adapt. For this purpose, different strategies of approaching maximal VT were tested.

Methods: Sixty-four Wistar rats received Escherichia coli lipopolysaccharide intratracheally.

Mesenchymal stromal cell therapy reduces lung inflammation and vascular remodeling and improves hemodynamics in experimental pulmonary arterial hypertension.

Background: Experimental research has reported beneficial effects of mesenchymal stromal cell (MSC) therapy in pulmonary arterial hypertension (PAH). However, these studies either were based on prophylactic protocols or assessed basic remodeling features without evaluating possible mechanisms. We analyzed the effects of MSC therapy on lung vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH.

Effects of pressure support and pressure-controlled ventilation on lung damage in a model of mild extrapulmonary acute lung injury with intra-abdominal hypertension.

Intra-abdominal hypertension (IAH) may co-occur with the acute respiratory distress syndrome (ARDS), with significant impact on morbidity and mortality. Lung-protective controlled mechanical ventilation with low tidal volume and positive end-expiratory pressure (PEEP) has been recommended in ARDS. However, mechanical ventilation with spontaneous breathing activity may be beneficial to lung function and reduce lung damage in mild ARDS.

Sevoflurane, Compared With Isoflurane, Minimizes Lung Damage in Pulmonary but Not in Extrapulmonary Acute Respiratory Distress Syndrome in Rats.

Background: Volatile anesthetics modulate inflammation in acute respiratory distress syndrome (ARDS). However, it is unclear whether they act differently depending on ARDS etiology. We hypothesized that the in vivo and in vitro effects of sevoflurane and isoflurane on lung damage would not differ in pulmonary (p) and extrapulmonary (exp) ARDS.

Lung Functional and Biologic Responses to Variable Ventilation in Experimental Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome.

Objectives: The biologic effects of variable ventilation may depend on the etiology of acute respiratory distress syndrome. We compared variable and conventional ventilation in experimental pulmonary and extrapulmonary acute respiratory distress syndrome.

Design: Prospective, randomized, controlled experimental study.

Biological Impact of Transpulmonary Driving Pressure in Experimental Acute Respiratory Distress Syndrome.

Background: Ventilator-induced lung injury has been attributed to the interaction of several factors: tidal volume (VT), positive end-expiratory pressure (PEEP), transpulmonary driving pressure (difference between transpulmonary pressure at end-inspiration and end-expiration, ΔP,L), and respiratory system plateau pressure (Pplat,rs).

Methods: Forty-eight Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, animals were randomized into combinations of VT and PEEP, yielding three different ΔP,L levels: ΔP,LLOW (VT = 6 ml/kg, PEEP = 3 cm H2O); ΔP,LMEAN (VT = 13 ml/kg, PEEP = 3 cm H2O or VT = 6 ml/kg, PEEP = 9.