Vaporized Perfluorohexane Attenuates Ventilator-induced Lung Injury in Isolated, Perfused Rabbit Lungs

2005 ◽  
Vol 102 (3) ◽  
pp. 597-605 ◽  
Author(s):  
Marcelo Gama de Abreu ◽  
Beate Wilmink ◽  
Matthias Hübler ◽  
Thea Koch
Keyword(s):  
Lung Injury ◽  
Therapy Group ◽  
Peak Inspiratory Pressure ◽  
Thromboxane B2 ◽  
Inspiratory Pressure ◽  
Control Group ◽  
Positive End Expiratory Pressure ◽  
Lung Weight ◽  
Ventilator Induced Lung Injury ◽  
Perfusate Flow

Background The authors tested the hypothesis that administration of vaporized perfluorohexane may attenuate ventilator-induced lung injury. Methods In isolated, perfused rabbit lungs, airway pressure-versus-time curves were recorded. At baseline, peak inspiratory pressure and positive end-expiratory pressure of mechanically ventilated lungs were set to obtain straight pressure-versus-time curves in both the lower and upper ranges, which are associated with less collapse and overdistension, respectively. After that, peak inspiratory pressure and positive end-expiratory pressure were set at 30 cm H2O and 0, respectively, and animals were randomly assigned to one of two groups: (1) simultaneous administration of 14% perfluorohexane vapor in room air (n = 7) and (2) control group-ventilation with room air (n = 7). After 20 min of cycling collapse and overdistension, tidal volume and positive end-expiratory pressure were set back to baseline levels, administration of perfluorohexane in the therapy group was stopped, and mechanical ventilation was continued for up to 60 min. Lung weight, mean pulmonary artery pressure, and concentration of thromboxane B2 in the perfusate were measured. In addition, the distribution of pulmonary perfusate flow was assessed by using fluorescent-labeled microspheres. Results Significantly higher peak inspiratory values developed in control lungs than in lungs treated with perfluorohexane. In addition, upper ranges of pressure-versus-time curves were closer to straight lines in the perfluorohexane group. Lung weight, mean pulmonary arterial pressure, and release of thromboxane B2 were significantly higher in controls than in perfluorohexane-treated lungs. Also, redistribution of pulmonary perfusate flow from caudal to cranial zones was less important in the treatment group. Conclusion The authors conclude that the administration of perfluorohexane vapor attenuates the development of ventilator-induced lung injury in isolated, perfused rabbit lungs.

Acute lung injury from mechanical ventilation at moderately high airway pressures

1990 ◽  
Vol 69 (3) ◽  
pp. 956-961 ◽  
Author(s):  
K. Tsuno ◽  
P. Prato ◽  
T. Kolobow
Keyword(s):  
Mechanical Ventilation ◽  
Peak Inspiratory Pressure ◽  
Blood Gases ◽  
Inspiratory Pressure ◽  
Control Group ◽  
Arterial Blood Gases ◽  
Lung Weight ◽  
Pulmonary Atelectasis ◽  
Arterial Pco2 ◽  
Arterial Blood

We have explored adverse pulmonary effects of mechanical ventilation at a peak inspiratory pressure of 30 cmH2O in paralyzed and anesthetized healthy sheep. A control group of eight sheep (group A) was mechanically ventilated with 40% oxygen at a tidal volume of 10 ml/kg, a frequency of 15 breaths/min, a peak inspiratory pressure less than 18 cmH2O, and a positive end-expiratory pressure of 3-5 cmH2O. During the ensuing 48 h, there were no measurable deleterious changes in lung function or arterial blood gases. Another 19 sheep were ventilated with 40% oxygen at a peak inspiratory pressure of 30 cmH2O under a different set of conditions and were randomly assigned to two groups. In group B, the respiratory rate was kept near 4 breaths/min to keep arterial PCO2 in the normal range; in group C, the frequency was kept near 15 breaths/min by including a variable dead space in the ventilator circuit to keep arterial PCO2 near baseline values. There was a progressive deterioration in total static lung compliance, functional residual capacity, and arterial blood gases. After some hours, there were abnormal chest roentgenographic changes. At time of death we found severe pulmonary atelectasis, increased wet lung weight, and an increase in the minimum surface tension of saline lung lavage fluid.

Effects of melatonin in an experimental model of ventilator-induced lung injury

2008 ◽  
Vol 295 (5) ◽  
pp. L820-L827 ◽  
Author(s):  
Paula R. Pedreira ◽  
Emilio García-Prieto ◽  
Diego Parra ◽  
Aurora Astudillo ◽  
Elena Diaz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Matrix Metalloproteinases ◽  
Lung Injury ◽  
Weight Ratio ◽  
Peak Inspiratory Pressure ◽  
Lung Damage ◽  
Inspiratory Pressure ◽  
Ventilator Induced Lung Injury ◽  
Tnf Α ◽  
Anti Inflammatory

Melatonin is a free radical scavenger and a broad-spectrum antioxidant and has well-documented immunomodulatory effects. We studied the effects of this hormone on lung damage, oxidative stress, and inflammation in a model of ventilator-induced lung injury (VILI), using 8- to 12-wk-old Swiss mice ( n = 48). Animals were randomized into three experimental groups: control (not ventilated); low-pressure ventilation [peak inspiratory pressure 15 cmH2O, positive end-expiratory pressure (PEEP) 2 cmH2O], and high-pressure ventilation (peak inspiratory pressure 25 cmH2O, PEEP 0 cmH2O). Each group was divided into two subgroups: eight animals were treated with melatonin (10 mg/kg ip, 30 min before the onset of ventilation) and the remaining eight with vehicle. After 2 h of ventilation, lung injury was evaluated by gas exchange, wet-to-dry weight ratio, and histological analysis. Levels of malondialdehyde, glutathione peroxidase, interleukins IL-1β, IL-6, TNF-α, and IL-10, and matrix metalloproteinases 2 and 9 in lung tissue were measured as indicators of oxidation status, pro-/anti-inflammatory cytokines, and matrix turnover, respectively. Ventilation with high pressures induced severe lung damage and release of TNF-α, IL-6, and matrix metalloproteinase-9. Treatment with melatonin improved oxygenation and decreased histological lung injury but significantly increased oxidative stress quantified by malondialdehyde levels. There were no differences in TNF-α, IL-1β, IL-6, or matrix metalloproteinases caused by melatonin treatment, but IL-10 levels were significantly higher in treated animals. These results suggest that melatonin decreases VILI by increasing the anti-inflammatory response despite an unexpected increase in oxidative stress.

Extreme hypoventilation reduces ventilator-induced lung injury during ventilation with low positive end-expiratory pressure in saline-lavaged rabbits

1998 ◽  
Vol 26 (10) ◽  
pp. 1690-1697 ◽  
Author(s):  
Keith G. Hickling ◽  
Timothy Wright ◽  
Keith Laubscher ◽  
Ian G. Town ◽  
Andrew Tie ◽  
...  
Keyword(s):  
Lung Injury ◽  
Positive End Expiratory Pressure ◽  
Ventilator Induced Lung Injury

A Metabolomic Approach to the Pathogenesis of Ventilator-induced Lung Injury

2014 ◽  
Vol 120 (3) ◽  
pp. 694-702 ◽  
Author(s):  
José L. Izquierdo-García ◽  
Shama Naz ◽  
Nicolás Nin ◽  
Yeny Rojas ◽  
Marcela Erazo ◽  
...  
Keyword(s):  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Tidal Volume ◽  
Lung Tissue ◽  
Metabolic Profiling ◽  
Metabolic Profile ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Positive End Expiratory Pressure ◽  
Ventilator Induced Lung Injury

Abstract Background: Global metabolic profiling using quantitative nuclear magnetic resonance spectroscopy (MRS) and mass spectrometry (MS) is useful for biomarker discovery. The objective of this study was to discover biomarkers of acute lung injury induced by mechanical ventilation (ventilator-induced lung injury [VILI]), by using MRS and MS. Methods: Male Sprague–Dawley rats were subjected to two ventilatory strategies for 2.5 h: tidal volume 9 ml/kg, positive end-expiratory pressure 5 cm H2O (control, n = 14); and tidal volume 25 ml/kg and positive end-expiratory pressure 0 cm H2O (VILI, n = 10). Lung tissue, bronchoalveolar lavage fluid, and serum spectra were obtained by high-resolution magic angle spinning and 1H-MRS. Serum spectra were acquired by high-performance liquid chromatography coupled to quadupole-time of flight MS. Principal component and partial least squares analyses were performed. Results: Metabolic profiling discriminated characteristics between control and VILI animals. As compared with the controls, animals with VILI showed by MRS higher concentrations of lactate and lower concentration of glucose and glycine in lung tissue, accompanied by increased levels of glucose, lactate, acetate, 3-hydroxybutyrate, and creatine in bronchoalveolar lavage fluid. In serum, increased levels of phosphatidylcholine, oleamide, sphinganine, hexadecenal and lysine, and decreased levels of lyso-phosphatidylcholine and sphingosine were identified by MS. Conclusions: This pilot study suggests that VILI is characterized by a particular metabolic profile that can be identified by MRS and MS. The metabolic profile, though preliminary and pending confirmation in larger data sets, suggests alterations in energy and membrane lipids. SUPPLEMENTAL DIGITAL CONTENT IS AVAILABLE IN THE TEXT

scholarly journals Inhibition of Poly(Adenosine Diphosphate–Ribose) Polymerase Attenuates Ventilator-induced Lung Injury

2008 ◽  
Vol 108 (2) ◽  
pp. 261-268 ◽  
Author(s):  
Rosanna Vaschetto ◽  
Jan W. Kuiper ◽  
Shyh Ren Chiang ◽  
Jack J. Haitsma ◽  
Jonathan W. Juco ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Tidal Volume ◽  
Interleukin 6 ◽  
Inflammatory Responses ◽  
Adenosine Diphosphate ◽  
High Tidal Volume ◽  
Positive End Expiratory Pressure ◽  
Ventilator Induced Lung Injury ◽  
Pharmacologic Inhibition

Background Mechanical ventilation can induce organ injury associated with overwhelming inflammatory responses. Excessive activation of poly(adenosine diphosphate-ribose) polymerase enzyme after massive DNA damage may aggravate inflammatory responses. Therefore, the authors hypothesized that the pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase by PJ-34 would attenuate ventilator-induced lung injury. Methods Anesthetized rats were subjected to intratracheal instillation of lipopolysaccharide at a dose of 6 mg/kg. The animals were then randomly assigned to receive mechanical ventilation at either low tidal volume (6 ml/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (15 ml/kg) with zero positive end-expiratory pressure, in the presence and absence of intravenous administration of PJ-34. Results The high-tidal-volume ventilation resulted in an increase in poly(adenosine diphosphate-ribose) polymerase activity in the lung. The treatment with PJ-34 maintained a greater oxygenation and a lower airway plateau pressure than the vehicle control group. This was associated with a decreased level of interleukin 6, active plasminogen activator inhibitor 1 in the lung, attenuated leukocyte lung transmigration, and reduced pulmonary edema and apoptosis. The administration of PJ-34 also decreased the systemic levels of tumor necrosis factor alpha and interleukin 6, and attenuated the degree of apoptosis in the kidney. Conclusion The pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase reduces ventilator-induced lung injury and protects kidney function.

scholarly journals NADPH Oxidase 4 Signaling in a Ventilator-induced Lung Injury Mouse Model

2021 ◽  
Author(s):  
Sang Hoon Lee ◽  
Mi Hwa Shin ◽  
Ah Young Leem ◽  
Su Hwan Lee ◽  
Kyung Soo Chung ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lavage Fluid ◽  
Lung Damage ◽  
Control Group ◽  
Group 4 ◽  
Ventilator Induced Lung Injury ◽  
Cell Counts ◽  
Group 5 ◽  
Group 2

Abstract For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. We investigated the role of NOX4 in a ventilator-induced lung injury (VILI) model.Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined.In the NOX4 inhibitor group, cell counts and protein concentrations from BALF were significantly lower than those in the HTV group (both, p<0.001). In the NOX4 KO group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (p<0.001). NOX4 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the ICU.In the VILI model, it may be possible to block VILI using NOX4 antibodies.

Determinants of gas flow through a bronchopleural fistula

1989 ◽  
Vol 67 (4) ◽  
pp. 1591-1596 ◽  
Author(s):  
M. C. Walsh ◽  
W. A. Carlo
Keyword(s):  
Airway Pressure ◽  
Gas Flow ◽  
Bronchopleural Fistula ◽  
Peak Inspiratory Pressure ◽  
Intrathoracic Pressure ◽  
Transpulmonary Pressure ◽  
Inspiratory Pressure ◽  
Positive End Expiratory Pressure ◽  
Inspiratory Time ◽  
Mean Airway Pressure

To assess the determinants of bronchopleural fistula (BPF) flow, we used a surgically created BPF to study 15 anesthetized intubated mechanically ventilated New Zealand White rabbits. Mean airway pressure and intrathoracic pressure were evaluated independently. Mean airway pressure was varied (8, 10, or 12 cmH2O) by independent manipulations of either peak inspiratory pressure, positive end-expiratory pressure, or inspiratory time. Intrathoracic pressure was varied from 0 to -40 cmH2O. BPF flow varied directly with mean airway pressure (P less than 0.001). However, at constant mean airway pressure, BPF flow was not influenced independently by changes in peak inspiratory pressure, positive end-expiratory pressure, or inspiratory time. Resistance of the BPF increased as intrathoracic pressure became more negative. Despite increased resistance, BPF flow also increased. BPF resistance was constant over the range of mean airway (P less than 0.01) pressures investigated. Our data document the influence of mean airway pressure and intrathoracic pressure on BPF flow and suggest that manipulations which reduce transpulmonary pressure will decrease BPF flow.

Air embolism with positive-pressure ventilation of rats

1977 ◽  
Vol 42 (3) ◽  
pp. 368-371 ◽  
Author(s):  
D. K. Kao ◽  
D. F. Tierney
Keyword(s):  
Lung Injury ◽  
Hemorrhagic Shock ◽  
Pulmonary Edema ◽  
Positive Pressure Ventilation ◽  
Peak Inspiratory Pressure ◽  
Oxygen Toxicity ◽  
Air Embolism ◽  
Inspiratory Pressure ◽  
Positive Pressure ◽  
Edema Fluid

Although air embolism is known to occur in humans and animals when the lung is overdistended, very few cases have been reported to be associated with positive-pressure ventilation. We have observed that air embolism occurs in rats ventilated with high inspiratory pressures (70 cmH2O) associated with high end-expiratory pressures (10 cmH2O). However, it does not occur in normal rats if the end-expiratory pressure is less than 5 cmH2O or the peak inspiratory pressure is below 60 cmH2O when the frequency of ventilation is 30. Hemorrhagic shock predisposes to air embolism, whereas conditions with pulmonary edema (fluid overloading, lung injury from ventilation with high inspiratory and low expiratory pressures, or oxygen toxicity) decrease the probability of its occurrence.

Mechanical Power and Development of Ventilator-induced Lung Injury

2016 ◽  
Vol 124 (5) ◽  
pp. 1100-1108 ◽  
Author(s):  
Massimo Cressoni ◽  
Miriam Gotti ◽  
Chiara Chiurazzi ◽  
Dario Massari ◽  
Ilaria Algieri ◽  
...  
Keyword(s):  
Lung Injury ◽  
Respiratory Rate ◽  
Transpulmonary Pressure ◽  
Lung Parenchyma ◽  
Plateau Pressure ◽  
Mechanical Power ◽  
Lung Edema ◽  
Lung Weight ◽  
Ventilator Induced Lung Injury ◽  
Power Threshold

Abstract Background The ventilator works mechanically on the lung parenchyma. The authors set out to obtain the proof of concept that ventilator-induced lung injury (VILI) depends on the mechanical power applied to the lung. Methods Mechanical power was defined as the function of transpulmonary pressure, tidal volume (TV), and respiratory rate. Three piglets were ventilated with a mechanical power known to be lethal (TV, 38 ml/kg; plateau pressure, 27 cm H2O; and respiratory rate, 15 breaths/min). Other groups (three piglets each) were ventilated with the same TV per kilogram and transpulmonary pressure but at the respiratory rates of 12, 9, 6, and 3 breaths/min. The authors identified a mechanical power threshold for VILI and did nine additional experiments at the respiratory rate of 35 breaths/min and mechanical power below (TV 11 ml/kg) and above (TV 22 ml/kg) the threshold. Results In the 15 experiments to detect the threshold for VILI, up to a mechanical power of approximately 12 J/min (respiratory rate, 9 breaths/min), the computed tomography scans showed mostly isolated densities, whereas at the mechanical power above approximately 12 J/min, all piglets developed whole-lung edema. In the nine confirmatory experiments, the five piglets ventilated above the power threshold developed VILI, but the four piglets ventilated below did not. By grouping all 24 piglets, the authors found a significant relationship between the mechanical power applied to the lung and the increase in lung weight (r2 = 0.41, P = 0.001) and lung elastance (r2 = 0.33, P &lt; 0.01) and decrease in Pao2/Fio2 (r2 = 0.40, P &lt; 0.001) at the end of the study. Conclusion In piglets, VILI develops if a mechanical power threshold is exceeded.

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