scholarly journals Respiratory and Systemic Effects of LASSBio596 Plus Surfactant in Experimental Acute Respiratory Distress Syndrome

2016 ◽  
Vol 38 (2) ◽  
pp. 821-835 ◽  
Author(s):  
Johnatas Dutra Silva ◽  
Gisele Pena de Oliveira ◽  
Cynthia dos Santos Samary ◽  
Carla Cristina Araujo ◽  
Gisele de Araujo Padilha ◽  
...  
Keyword(s):  
Surface Tension ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Cecal Ligation ◽  
Exogenous Surfactant ◽  
Experimental Sepsis ◽  
Apoptosis Protein ◽  
Anti Inflammatory

Background/Aims: Exogenous surfactant has been proposed as adjunctive therapy for acute respiratory distress syndrome (ARDS), but it is inactivated by different factors present in the alveolar space. We hypothesized that co-administration of LASSBio596, a molecule with significant anti-inflammatory properties, and exogenous surfactant could reduce lung inflammation, thus enabling the surfactant to reduce edema and improve lung function, in experimental ARDS. Methods: ARDS was induced by cecal ligation and puncture surgery in BALB/c mice. A sham-operated group was used as control (CTRL). After surgery (6 hours), CTRL and ARDS animals were assigned to receive: (1) sterile saline solution; (2) LASSBio596; (3) exogenous surfactant or (4) LASSBio596 plus exogenous surfactant (n = 22/group). Results: Regardless of exogenous surfactant administration, LASSBio596 improved survival rate and reduced collagen fiber content, total number of cells and neutrophils in PLF and blood, cell apoptosis, protein content in BALF, and urea and creatinine levels. LASSBio596 plus surfactant yielded all of the aforementioned beneficial effects, as well as increased BALF lipid content and reduced surface tension. Conclusion: LASSBio596 exhibited major anti-inflammatory and anti-fibrogenic effects in experimental sepsis-induced ARDS. Its association with surfactant may provide further advantages, potentially by reducing surface tension.

scholarly journals Sulforhodamine B and exogenous surfactant effects on alveolar surface tension under acute respiratory distress syndrome conditions

2020 ◽  
Vol 129 (6) ◽  
pp. 1505-1513 ◽  
Author(s):  
Tam L. Nguyen ◽  
Carrie E. Perlman
Keyword(s):  
Surface Tension ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Exogenous Surfactant ◽  
Sulforhodamine B ◽  
Isolated Lungs ◽  
Surfactant Effects ◽  
Alveolar Surface

In the acute respiratory distress syndrome (ARDS), lowering surface tension, T, should reduce ventilation injury, yet exogenous surfactant has not reduced mortality. We show with direct T determination in isolated lungs that substances suggested to elevate T in ARDS indeed raise T, and exogenous surfactant reduces T. Further, we extend our previous finding that sulforhodamine B (SRB) reduces T below normal in healthy lungs and show that SRB, too, reduces T under ARDS conditions.

scholarly journals Sulforhodamine B and exogenous surfactant effects on alveolar surface tension under acute respiratory distress syndrome conditions

2020 ◽  
Author(s):  
Tam L. Nguyen ◽  
Carrie E. Perlman
Keyword(s):  
Surface Tension ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Exogenous Surfactant ◽  
Sulforhodamine B ◽  
Surfactant Activity ◽  
Isolated Lungs ◽  
Alveolar Surface

AbstractIn the acute respiratory distress syndrome (ARDS), alveolar surface tension, T, may be elevated. Elevated T should increase ventilation-induced lung injury. Exogenous surfactant therapy, intended to lower T, has not reduced mortality. Sulforhodamine B (SRB) might, alternatively, be employed to lower T. We test whether substances suspected of elevating T in ARDS raise T in the lungs and test the abilities of exogenous surfactant and SRB to reduce T. In isolated rat lungs, we micropuncture a surface alveolus and instill a solution of a purported T-raising substance: control saline, cell debris, secretory phospholipase A2 (sPLA2), acid or mucins. We test each substance alone; with albumin, to model proteinaceous edema liquid; with albumin and exogenous surfactant; or with albumin and SRB. We determine T in situ in the lungs by combining servo-nulling pressure measurement with confocal microscopy, and applying the Laplace relation. With control saline, albumin does not alter T, additional surfactant raises T and additional SRB lowers T. The experimental substances, without or with albumin, raise T. Excepting under aspiration conditions, addition of surfactant or SRB lowers T. Exogenous surfactant activity is concentration and ventilation dependent. Sulforhodamine B, which could be delivered intravascularly, holds promise as an alternative therapeutic.New and NoteworthyIn the acute respiratory distress syndrome (ARDS), lowering surface tension, T, should reduce ventilation injury yet exogenous surfactant has not reduced mortality. We show with direct T-determination in isolated lungs that substances suggested to elevate T in ARDS indeed raise T, and exogenous surfactant reduces T. Further, we extend our previous finding that sulforhodamine B (SRB) reduces T below normal in healthy lungs and show that SRB, too, reduces T under ARDS conditions.

scholarly journals Exogenous Surfactant Therapy for Pediatric Patients with Acute Respiratory Distress Syndrome

1997 ◽  
Vol 4 (1) ◽  
pp. 21-26 ◽  
Author(s):  
James F Lewis ◽  
Jasvinder S Dhillon ◽  
Ram N Singh ◽  
Craig C Johnson ◽  
Timothy C Frewen
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Pilot Study ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Pediatric Patients ◽  
Distress Syndrome ◽  
Exogenous Surfactant ◽  
Lung Dysfunction ◽  
Surfactant Administration ◽  
Severe Lung

Exogenous surfactant administration is currently being tested in patients with the acute respiratory distress syndrome (ARDS). The results of the studies have varied because several factors may influence the host’s response to this therapy. This clinical pilot study was designed to evaluate the safety and efficacy of exogenous surfactant administration in pediatric patients with ARDS. Surfactant was administered to 13 patients with severe lung dysfunction, and eight of these patients experienced a significant improvement in oxygenation after the first dose of surfactant. In these patients the exogenous surfactant was administered within 48 h of the diagnosis of ARDS, whereas in the five patients who did not respond, surfactant was administered several days after the onset of ARDS. Responders also spent fewer days on a mechanical ventilator and less time in intensive care compared with nonresponders. Based on the results of this pilot study, a more appropriate multicentre clinical trial should be designed to evaluate this treatment strategy.

scholarly journals Effect of low-dose exogenous surfactant on infants with acute respiratory distress syndrome after cardiac surgery: A retrospective analysis

2020 ◽  
Author(s):  
Rongyuan Zhang ◽  
Xu Wang ◽  
Shoujun Li ◽  
Jun Yan
Keyword(s):  
Cardiac Surgery ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Standard Therapy ◽  
Low Dose ◽  
Distress Syndrome ◽  
Exogenous Surfactant ◽  
Control Group ◽  
Surfactant Treatment

Abstract Background: To evaluate the effect of low-dose exogenous surfactant therapy on infants suffering acute respiratory distress syndrome (ARDS) after cardiac surgery. Methods: We conducted a retrospective case-control study of infants diagnosed with moderate-severe ARDS after cardiac surgery. A case was defined as a patient that received surfactant and standard therapy, while a control was defined as a patient that underwent standard therapy. The primary endpoint was the improvement in oxygenation index (OI) after 24-hour of surfactant treatment; and secondary endpoints were the ventilator time and PICU time. Results: 22 infants treated with surfactant were matched with 22 controls. Early low-dose (20mg/kg) surfactant treatment was associated with improved outcomes. After surfactant administration for 24-hour, the surfactant group was much better compared with the control group at the 24-hour in OI (difference in average change from baseline, -6.7 [95% CI, -9.3 to -4.1]) (P < 0.01) and VI (mean difference, -11.9 [95% CI, -18.1 to -5.7]) (P < 0.01). Ventilation time and PICU time were significantly shorter in the surfactant group compared with the control group (133.6h±27.2 vs 218.4h±28.7, P < 0.01 ; 10.7d±5.1 vs 17.5d±6.8, P < 0.01). Infants in the surfactant group under 3 months benefit more from OI and VI than the infants over 3 months in a preliminary exploratory analysis.Conclusions: In infants with moderate-severe ARDS after cardiac surgery, early low-dose exogenous surfactant treatment could prominently improve oxygenation and reduce mechanical ventilation time and PICU time. Infants younger than 3 months may get more benefit of oxygenation than the older ones.

scholarly journals Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency

2020 ◽  
Author(s):  
Huang-Ping Yu ◽  
Fu-Chao Liu ◽  
Ani Umoro ◽  
Zih-Chan Lin ◽  
Ahmed O. Elzoghby ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Oleic Acid ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Inflammatory Activity ◽  
Human Neutrophils ◽  
Essential Property ◽  
Anti Inflammatory

Abstract Background: Oleic acid (OA) is reported to show anti-inflammatory activity toward activated neutrophils. It is also an important material in nanoparticles for increased stability and cellular internalization. We aimed to evaluate the anti-inflammatory activity of injectable OA-based nanoparticles for treating lung injury. Different sizes of nanocarriers were prepared to explore the effect of nanoparticulate size on inflammation inhibition. Results: The nanoparticles were fabricated with the mean diameters of 105, 153, and 225 nm. The nanocarriers were ingested by isolated human neutrophils during a 5-min period, with the smaller sizes exhibiting greater uptake. The size reduction led to the decrease of cell viability and the intracellular calcium level. The OA-loaded nanosystems dose-dependently suppressed the superoxide anion and elastase produced by the stimulated neutrophils. The inhibition level was comparable for the nanoparticles of different sizes. In the ex vivo biodistribution study, the pulmonary accumulation of nanoparticles increased following the increase of particle size. The nanocarriers were mainly excreted by the liver and bile clearance. Mice were exposed to intratracheal lipopolysaccharide (LPS) to induce acute respiratory distress syndrome (ARDS), like lung damage. The lipid-based nanocarriers mitigated myeloperoxidase (MPO) and cytokines more effectively as compared to OA solution. The larger nanoparticles displayed greater reduction on MPO, TNF-α, and IL-6 than the smaller ones. The histology confirmed the decreased pulmonary neutrophil recruitment and lung-architecture damage after intravenous administration of larger nanoparticles. Conclusions: Nanoparticulate size, an essential property governing the anti-inflammatory effect and lung-injury therapy, had different effects on activated neutrophil inhibition and in vivo therapeutic efficacy.

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