Abstract
Ventilator induced lung injury (VILI) is a lung injury syndrome associated with mechanical ventilation, most frequently for treatment of Acute Lung Injury (ALI), and generally secondary to the use of greater than physiologic tidal volumes. To reproduce this syndrome experimentally, C57Bl/6 mice were intubated and ventilated with low (4 mL/Kg body weight) or high (12 mL/Kg) tidal volume for 6 h. Lung parameters with low volume ventilation were unchanged from non-ventilated (control) mice. High tidal volume ventilation resulted in marked lung injury with increased neutrophils in the bronchoalveolar lavage fluid (BALf) indicating lung inflammation, increase in both protein in BALf and lung dry/wet weight indicating lung edema, increased lung thiobarbituric acid reactive substances (TBARS) and 8-isoprostanes indicating lung lipid peroxidation, and increased lung protein carbonyls indicating protein oxidation. Either intratracheal or intravenous pretreatment of mice with a 9 amino acid peptide called peroxiredoxin 6 inhibitor peptide-2 (PIP-2) significantly reduced all parameters of lung injury by ~50–80%. PIP-2 inhibits NADPH oxidase type 2 (NOX2) activation. We propose that PIP-2 does not affect the mechanically induced lung damage component of VILI but does significantly reduce the secondary inflammatory component.
Highlights
This approach can lead to the use of large tidal volumes with resultant high intrapulmonary pressures that can result in lung damage and augment the lung injury associated with the primary lung disease [6,7,8]
We found that a lipid inhibitor (MJ33) of aiPLA2 activity or its genetic inactivation were effective in modulating LPS-induced or hyperoxia-mediated acute lung injury (ALI) in mice, providing evidence that aiPLA2 and subsequent NADPH oxidase type 2 (NOX2) activation plays an important role in ALI, at least in mice [22,23,24,25,26]
While the mechanically induced lung damage can be of varying severity, it can result in a result in a secondary inflammatory response that amplifies the tissue injury; this secondsecondary inflammatory response that amplifies the tissue injury; this secondary response ary response results in inappropriate activation of leukocytes and platelets and enhanced results in inappropriate activation of leukocytes and platelets and enhanced activation activation of coagulation signalsThis
Summary
The parameters of lung ventilation used in the early days of ARDS treatment were designed to obtain close to normal blood oxygenation while maintaining inspired oxygen levels within the non-toxic range [4,5]. This approach can lead to the use of large tidal volumes with resultant high intrapulmonary pressures that can result in lung damage (barotrauma) and augment the lung injury associated with the primary lung disease [6,7,8]
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