Variable ventilation induces endogenous surfactant release in normal guinea pigs

2003 ◽  
Vol 285 (2) ◽  
pp. L370-L375 ◽  
Author(s):  
Stephen P. Arold ◽  
Béla Suki ◽  
Adriano M. Alencar ◽  
Kenneth R. Lutchen ◽  
Edward P. Ingenito
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Protein Content ◽  
Guinea Pigs ◽  
Lung Lavage ◽  
Blood Oxygenation ◽  
Lung Mechanics ◽  
Control Group ◽  
Whole Lung Lavage ◽  
Variable Ventilation

Variable or noisy ventilation, which includes random breath-to-breath variations in tidal volume (Vt) and frequency, has been shown to consistently improve blood oxygenation during mechanical ventilation in various models of acute lung injury. To further understand the effects of variable ventilation on lung physiology and biology, we mechanically ventilated 11 normal guinea pigs for 3 h using constant-Vt ventilation ( n = 6) or variable ventilation ( n = 5). After 3 h of ventilation, each animal underwent whole lung lavage for determination of alveolar surfactant content and composition, while protein content was assayed as a possible marker of injury. Another group of animals underwent whole lung lavage in the absence of mechanical ventilation to serve as an unventilated control group ( n = 5). Although lung mechanics did not vary significantly between groups, we found that variable ventilation improved oxygenation, increased surfactant levels nearly twofold, and attenuated alveolar protein content compared with animals ventilated with constant Vt. These data demonstrate that random variations in Vt promote endogenous release of biochemically intact surfactant, which improves alveolar stability, apparently reducing lung injury.

Design of a new variable-ventilation method optimized for lung recruitment in mice

2008 ◽  
Vol 104 (5) ◽  
pp. 1329-1340 ◽  
Author(s):  
Apiradee Thammanomai ◽  
Lauren E. Hueser ◽  
Arnab Majumdar ◽  
Erzsébet Bartolák-Suki ◽  
Béla Suki
Keyword(s):  
Lung Injury ◽  
Respiratory Mechanics ◽  
Dynamic Equilibrium ◽  
Blood Oxygenation ◽  
Lung Mechanics ◽  
Lung Collapse ◽  
Regional Lung ◽  
Variable Ventilation ◽  
Ventilation Modes ◽  
Ventilation Method

Variable ventilation (VV), characterized by breath-to-breath variation of tidal volume (Vt) and breathing rate (f), has been shown to improve lung mechanics and blood oxygenation during acute lung injury in many species compared with conventional ventilation (CV), characterized by constant Vt and f. During CV as well as VV, the lungs of mice tend to collapse over time; therefore, the goal of this study was to develop a new VV mode (VVN) with an optimized distribution of Vt to maximize recruitment. Groups of normal and HCl-injured mice were subjected to 1 h of CV, original VV (VVO), CV with periodic large breaths (CVLB), and VVN, and the effects of ventilation modes on respiratory mechanics, airway pressure, blood oxygenation, and IL-1β were assessed. During CV and VVO, normal and injured mice showed regional lung collapse with increased airway pressures and poor oxygenation. CVLB and VVN resulted in a stable dynamic equilibrium with significantly improved respiratory mechanics and oxygenation. Nevertheless, VVN provided a consistently better physiological response. In injured mice, VVO and VVN, but not CVLB, were able to reduce the IL-1β-related inflammatory response compared with CV. In conclusion, our results suggest that application of higher Vt values than the single Vt currently used in clinical situations helps stabilize lung function. In addition, variable stretch patterns delivered to the lung by VV can reduce the progression of lung injury due to ventilation in injured mice.

TGF-beta 1 causes increased endothelial ICAM-1 expression and lung injury

1994 ◽  
Vol 77 (3) ◽  
pp. 1281-1287 ◽  
Author(s):  
Y. Suzuki ◽  
T. Tanigaki ◽  
D. Heimer ◽  
W. Wang ◽  
W. G. Ross ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lung Injury ◽  
Transforming Growth Factor Beta ◽  
Guinea Pigs ◽  
Transforming Growth Factor ◽  
Weight Ratio ◽  
Control Group ◽  
High Dose ◽  
Albumin Concentration ◽  
Tgf Beta

Neutrophil adherence to vascular endothelium is partially mediated by adhesion molecules, including intracellular adhesion molecule 1 (ICAM-1), on endothelial cells. We examined the effect of transforming growth factor-beta 1 (TGF-beta 1) on the expression of ICAM-1 in human umbilical vein endothelial cells (HUVEC). TGF-beta 1 (1 ng/ml) increased ICAM-1 and ICAM-1 mRNA expression in HUVEC, as assessed by flow cytometry and Northern blot analysis, respectively. In addition, we investigated whether exogenous recombinant TGF-beta 1 can cause neutrophil-mediated lung injury in guinea pigs. The plasma half-life of 125I-labeled TGF-beta 1 in guinea pigs was 4.6 +/- 0.1 min, and the 125I activity was 2.8 +/- 0.2% 8 h after injection. The ratio of 125I-labeled albumin concentration in lung tissue and bronchoalveolar lavage (BAL) fluid to that in plasma, lung wet-to-dry weight ratio, numbers of neutrophils in BAL fluid, and numbers of neutrophils per alveolus in fixed lung sections increased in guinea pigs that received a high dose of TGF-beta 1 (25 micrograms i.v. followed by 2 micrograms/h for 8 h) compared with the control group. These results suggest that TGF-beta 1 causes neutrophil-mediated lung injury, possibly through upregulation of ICAM-1 on endothelial cells, and might be important in the pathogenesis of lung injury.

Serial segmental bronchoalveolar lavage in individual rats

1999 ◽  
Vol 87 (3) ◽  
pp. 1230-1233 ◽  
Author(s):  
Arthur E. Varner ◽  
Ronald L. Sorkness ◽  
Aparna Kumar ◽  
Michael R. Kaplan ◽  
Robert F. Lemanske
Keyword(s):  
Bronchoalveolar Lavage ◽  
Tracheal Tube ◽  
Mononuclear Cells ◽  
Pulmonary Inflammation ◽  
Left Lung ◽  
Lung Lavage ◽  
Lung Mechanics ◽  
Buffer Solution ◽  
Regional Variability ◽  
Whole Lung Lavage

Bronchoalveolar lavage (BAL) is a well-characterized technique for analysis of cellular constituents of the airways and air spaces, but whole lung lavage requires that the animal be euthanized. We describe a technique of segmental BAL in rats that allows serial measurements of inflammation. A tracheal tube was placed, under direct visualization, in lightly anesthetized animals, and a catheter was passed through the tracheal tube and advanced to a wedge position. Five 0.1-ml volumes of buffer solution were instilled and then withdrawn with gentle suction. In normal rats, the percentages of neutrophils, eosinophils, and mononuclear cells had a high level of agreement in the segmental samples compared with those obtained subsequently by whole lung lavage. In rats with acute pulmonary inflammation, the differential leukocyte counts from segmental samples exhibited patterns of change that differed from those of whole lung lavage; however, most segmental samples were obtained from the left lung base so that regional variability could be minimized in serial studies. Lung mechanics and airway inflammation were not affected by repeated segmental BALs done 2 wk apart.

Alterations to surfactant precede physiological deterioration during high tidal volume ventilation

2008 ◽  
Vol 294 (5) ◽  
pp. L974-L983 ◽  
Author(s):  
Adam A. Maruscak ◽  
Daniel W. Vockeroth ◽  
Brandon Girardi ◽  
Tanya Sheikh ◽  
Fred Possmayer ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Tidal Volume ◽  
Blood Oxygenation ◽  
Exogenous Surfactant ◽  
Ventilation Strategy ◽  
Adult Rats ◽  
Lung Dysfunction ◽  
And Function ◽  
Over Time

Lung injury due to mechanical ventilation is associated with an impairment of endogenous surfactant. It is unknown whether this impairment is a consequence of or an active contributor to the development and progression of lung injury. To investigate this issue, the present study addressed three questions: Do alterations to surfactant precede physiological lung dysfunction during mechanical ventilation? Which components are responsible for surfactant's biophysical dysfunction? Does exogenous surfactant supplementation offer a physiological benefit in ventilation-induced lung injury? Adult rats were exposed to either a low-stretch [tidal volume (Vt) = 8 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O, respiratory rate (RR) = 54–56 breaths/min (bpm), fractional inspired oxygen (FiO2) = 1.0] or high-stretch (Vt = 30 ml/kg, PEEP = 0 cmH2O, RR = 14–16 bpm, FiO2 = 1.0) ventilation strategy and monitored for either 1 or 2 h. Subsequently, animals were lavaged and the composition and function of surfactant was analyzed. Separate groups of animals received exogenous surfactant after 1 h of high-stretch ventilation and were monitored for an additional 2 h. High stretch induced a significant decrease in blood oxygenation after 2 h of ventilation. Alterations in surfactant pool sizes and activity were observed at 1 h of high-stretch ventilation and progressed over time. The functional impairment of surfactant appeared to be caused by alterations to the hydrophobic components of surfactant. Exogenous surfactant treatment after a period of high-stretch ventilation mitigated subsequent physiological lung dysfunction. Together, these results suggest that alterations of surfactant are a consequence of the ventilation strategy that impair the biophysical activity of this material and thereby contribute directly to lung dysfunction over time.

scholarly journals Effects of Various Modes of Mechanical Ventilation in Normal Rats

2014 ◽  
Vol 120 (4) ◽  
pp. 943-950 ◽  
Author(s):  
Matteo Pecchiari ◽  
Ario Monaco ◽  
Antonia Koutsoukou ◽  
Patrizia Della Valle ◽  
Guendalina Gentile ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Negative Pressure ◽  
Positive Pressure Ventilation ◽  
Lung Mechanics ◽  
Whole Body ◽  
Positive Pressure ◽  
Negative Pressure Ventilation ◽  
Cytokine Levels

Abstract Background: Recent studies in healthy mice and rats have reported that positive pressure ventilation delivered with physiological tidal volumes at normal end-expiratory volume worsens lung mechanics and induces cytokine release, thus suggesting that detrimental effects are due to positive pressure ventilation per se. The aim of this study in healthy animals is to assess whether these adverse outcomes depend on the mode of mechanical ventilation. Methods: Rats were subjected to 4 h of spontaneous, positive pressure, and whole-body or thorax-only negative pressure ventilation (N = 8 per group). In all instances the ventilatory pattern was that of spontaneous breathing. Lung mechanics, cytokines concentration in serum and broncho–alveolar lavage fluid, lung wet-to-dry ratio, and histology were assessed. Values from eight animals euthanized shortly after anesthesia served as control. Results: No evidence of mechanical ventilation–dependent lung injury was found in terms of lung mechanics, histology, or wet-to-dry ratio. Relative to control, cytokine levels and recruitment of polymorphonuclear leucocytes increased slightly, and to the same extent with spontaneous, positive pressure, and whole-body negative pressure ventilation. Thorax-only negative pressure ventilation caused marked chest and lung distortion, reversible increase of lung elastance, and higher polymorphonuclear leucocyte count and cytokine levels. Conclusion: Both positive and negative pressure ventilation performed with tidal volumes and timing of spontaneous, quiet breathing neither elicit an inflammatory response nor cause morpho-functional alterations in normal animals, thus supporting the notion of the presence of a critical volume threshold above which acute lung injury ensues. Distortion of lung parenchyma can induce an inflammatory response, even in the absence of volotrauma.

scholarly journals Chronic lung injury and impaired pulmonary function in a mouse model of acid ceramidase deficiency

2018 ◽  
Vol 314 (3) ◽  
pp. L406-L420 ◽  
Author(s):  
Fabian P. S. Yu ◽  
Diana Islam ◽  
Jakub Sikora ◽  
Shaalee Dworski ◽  
Jiří Gurka ◽  
...  
Keyword(s):  
Lung Function ◽  
Lung Injury ◽  
Mouse Model ◽  
Vascular Permeability ◽  
Phospholipid Composition ◽  
Blood Oxygenation ◽  
Lung Mechanics ◽  
Neurological Involvement ◽  
Lysosomal Storage ◽  
Acid Ceramidase

Farber disease (FD) is a debilitating lysosomal storage disorder (LSD) caused by a deficiency of acid ceramidase (ACDase) activity due to mutations in the gene ASAH1. Patients with ACDase deficiency may develop a spectrum of clinical phenotypes. Severe cases of FD are frequently associated with neurological involvement, failure to thrive, and respiratory complications. Mice homozygous ( Asah1P361R/P361R) for an orthologous patient mutation in Asah1 recapitulate human FD. In this study, we show significant impairment in lung function, including low compliance and increased airway resistance in a mouse model of ACDase deficiency. Impaired lung mechanics in Farber mice resulted in decreased blood oxygenation and increased red blood cell production. Inflammatory cells were recruited to both perivascular and peribronchial areas of the lung. We observed large vacuolated foamy histiocytes that were full of storage material. An increase in vascular permeability led to protein leakage, edema, and impacted surfactant homeostasis in the lungs of Asah1P361R/P361R mice. Bronchial alveolar lavage fluid (BALF) extraction and analysis revealed accumulation of a highly turbid lipoprotein-like substance that was composed in part of surfactants, phospholipids, and ceramides. The phospholipid composition of BALF from Asah1P361R/P361R mice was severely altered, with an increase in both phosphatidylethanolamine (PE) and sphingomyelin (SM). Ceramides were also found at significantly higher levels in both BALF and lung tissue from Asah1P361R/P361R mice when compared with levels from wild-type animals. We demonstrate that a deficiency in ACDase leads to sphingolipid and phospholipid imbalance, chronic lung injury caused by significant inflammation, and increased vascular permeability, leading to impaired lung function.

Protective mechanical ventilation does not exacerbate lung function impairment or lung inflammation following influenza A infection

2009 ◽  
Vol 107 (5) ◽  
pp. 1472-1478 ◽  
Author(s):  
Graeme R. Zosky ◽  
Vincenzo Cannizzaro ◽  
Zoltan Hantos ◽  
Peter D. Sly
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Influenza A ◽  
Airway Resistance ◽  
Inflammatory Cells ◽  
Lung Mechanics ◽  
Forced Oscillation Technique ◽  
Protective Ventilation Strategy ◽  
Protective Mechanical Ventilation ◽  
Tissue Elastance

The degree to which mechanical ventilation induces ventilator-associated lung injury is dependent on the initial acute lung injury (ALI). Viral-induced ALI is poorly studied, and this study aimed to determine whether ALI induced by a clinically relevant infection is exacerbated by protective mechanical ventilation. Adult female BALB/c mice were inoculated with 104.5 plaque-forming units of influenza A/Mem/1/71 in 50 μl of medium or medium alone. This study used a protective ventilation strategy, whereby mice were anesthetized, tracheostomized, and mechanically ventilated for 2 h. Lung mechanics were measured periodically throughout the ventilation period using a modification of the forced oscillation technique to obtain measures of airway resistance and coefficients of tissue damping and tissue elastance. Thoracic gas volume was measured and used to obtain specific airway resistance, tissue damping, and tissue elastance. At the end of the ventilation period, a bronchoalveolar lavage sample was collected to measure inflammatory cells, macrophage inflammatory protein-2, IL-6, TNF-α, and protein leak. Influenza infection caused significant increases in inflammatory cells, protein leak, and deterioration in lung mechanics that were not exacerbated by mechanical ventilation, in contrast to previous studies using bacterial and mouse-specific viral infection. This study highlighted the importance of type and severity of lung injury in determining outcome following mechanical ventilation.

scholarly journals Pre-treatment with Isoflurane or Sevoflurane is not protective against high tidal volume induced lung injury in rats

2019 ◽  
Author(s):  
Florian Setzer ◽  
Lars Hueter ◽  
Barbara Schmidt ◽  
Konrad Schwarzkopf ◽  
Torsten Schreiber
Keyword(s):  
Mechanical Ventilation ◽  
Body Weight ◽  
Lung Injury ◽  
Tidal Volume ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Protective Effects ◽  
Markers Of Inflammation ◽  
In Vivo Animal Model

Abstract Background Volatile anesthetics (VA) may exert organ-protective effects in various experimental and clinical settings. Mechanical ventilation (MV) induces an inflammatory response and, depending on the ventilator settings chosen, injury in the lungs. It is unclear if prophylactic inhaled VA applied on healthy lungs prior to MV are protective regarding these effects.Methods Healthy, spontaneously breathing rats were exposed for 30 minutes to either isoflurane (1.8 Vol %), sevoflurane (3.0 Vol %) or no VA (controls). Animals were allowed to recover and then mechanically ventilated for 4 hours with either high (21 ml/kg body weight) or low (9 ml/kg body weight) tidal volume. Cardiorespiratory parameters and systemic inflammation were assessed at the beginning and during mechanical ventilation. Cellular, non-cellular and histologic markers of pulmonary injury and inflammation were determined.Results Irrespective of VA pretreatment, MV with high VT negatively affected markers of lung integrity such as arterial oxygenation and lung wet-to-dry ratio. Regarding the application of VA pretreatment protective effects on lung function were absent but there were changes in some markers of inflammation such as a decrease in blood lymphocyte counts and an increase in interleukin 6 concentration in plasma and in lung lavage fluid. These effects were heterogeneous regarding group allocation and time points.Conclusions In this in in vivo animal model, prophylactic administration of inhaled VA was not beneficial or protective regarding ventilation induced lung injury. However, there were effects suggestive of a modulation of inflammatory markers associated with VA prophylaxis. The clinical or biological relevance of these findings so far remain unclear and should be subject to further studies.

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