Atelectasis causes alveolar hypoxia-induced inflammation during uneven mechanical ventilation in rats

Abstract

BackgroundPatients with acute respiratory distress syndrome receiving mechanical ventilation show inhomogeneous lung aeration. Atelectasis during uneven mechanical ventilation leads to alveolar hypoxia and could therefore result in lung inflammation and injury. We aimed to elucidate whether and how atelectasis causes alveolar hypoxia-induced inflammation during uneven mechanical ventilation in an open-chest differential-ventilation rat model.MethodsWe first investigated inflammatory and histological changes in the bilateral lungs of unilaterally ventilated rats, in which the right lung was atelectatic and the left lung was ventilated with high tidal volume (HTV). In the next series, we investigated the effects of normal tidal volume (NTV) ventilation of the right lungs with 60 % O2 or 100 % N2 during HTV ventilation of the left lungs. Then, proinflammatory cytokine secretions were quantified from murine lung epithelial (MLE15) and murine alveolar macrophage (MH-S) cells cultured under a hypoxic condition (5 % O2) mimicking atelectasis. Further, activities of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)-1 were assessed in the nonventilated atelectatic lung and MLE15 cells cultured under the hypoxic condition. Finally, effects of NF-κB inhibition and HIF-1α knockdown on the cytokine secretions from MLE15 cells cultured under the hypoxic condition were assessed.ResultsThe nonventilated atelectatic lungs showed inflammatory responses and minimal histological changes comparable to those of the HTV-ventilated lungs. NTV ventilation with 60 % O2 attenuated the increase in chemokine (C-X-C motif) ligand (CXCL)-1 secretion and neutrophil accumulation observed in the atelectatic lungs, but that with 100 % N2 did not. MLE15 cells cultured with tumor necrosis factor (TNF)-α under the hypoxic condition showed increased CXCL-1 secretion. NF-κB and HIF-1α were activated in the nonventilated atelectatic lungs and MLE15 cells cultured under the hypoxic condition. NF-κB inhibition abolished the hypoxia-induced increase in CXCL-1 secretion from MLE15 cells, while HIF-1α knockdown augmented it.ConclusionsAtelectasis causes alveolar hypoxia-induced inflammatory responses including NF-κB-dependent CXCL-1 secretion from lung epithelial cells. HIF-1 activation in lung epithelial cells is an anti-inflammatory response to alveolar hypoxia in atelectatic lungs.

Fast track in thoracic surgery and anaesthesia

“…Application of low-level continuous positive airway pressure (2 cm H 2 O) to the collapsed lung avoids dense atelectasis and minimizes intrapulmonary shunt but will not impair surgical exposure. This management has been demonstrated to reduce hypoxia-induced alveolar inflammatory response in animal models of one-lung ventilation [51]. Protective ventilation during thoracic surgery reduces acute lung injury.…”

The effects of protective lung ventilation on regional cerebral oxygen saturation in intracranial tumor operation during dura opening: study protocol for a randomized controlled trial

“…Relevant studies suggest that low tidal volume combined with positive end-expiratory pressure (PEEP) ventilation and alveolar recruitment maneuver (ARM) is the most widely used PLV strategy, and it can reduce lung volume damage and pulmonary barotrauma, improve pulmonary function, and decrease postoperative pulmonary complications [9]. Theoretically, low tidal volume prevents excessive alveolar expansion [10], and higher PEEP prevents pulmonary atelectasis [11]. However, gradually increased PEEP to the level of 20 cm H 2 O or even higher is often needed in traditional PLV strategies [5,9] which will obviously affect the circulation and intracranial pressure (ICP) of patients [12] and may increase airway pressure and reduce cerebral venous reflux and intraoperative operating space, thus limiting its application in patients with craniotomy.…”

The effects of protective lung ventilation on regional cerebral oxygen saturation in intracranial tumor operation during dura opening：study protocol for a randomized controlled trial.

“…Relevant studies suggest that low-tide volume combined with positive end-expiratory pressure (PEEP) ventilation and alveolar recruitment maneuver (ARM) is the most widely used lung protective ventilation strategy, which can reduce lung volume damage and pulmonary barotrauma, improve pulmonary function and decrease postoperative pulmonary complications [9]. Theoretically, low tide volume prevents excessive alveolar expansion [10] and higher PEEP prevents pulmonary atelectasis [11]. However, gradually increased PEEP to the level of 20 cm H 2 O or even higher is often needed in traditional protective lung ventilation strategies [5,9] which will obviously affect the circulation and intracranial pressure of patients [12], and may increase airway pressure, reduce cerebral venous reflux and intraoperative operating space, thus limiting its application in patients with craniotomy.…”