Cytokine release, small airway injury, and parenchymal damage during mechanical ventilation in normal open-chest rats

Abstract

Lung morpho-functional alterations and inflammatory response to various types of mechanical ventilation (MV) have been assessed in normal, anesthetized, open-chest rats. Measurements were taken during protective MV [tidal volume (Vt) = 8 ml/kg; positive end-expiratory pressure (PEEP) = 2.6 cmH(2)O] before and after a 2- to 2.5-h period of ventilation on PEEP (control group), zero EEP without (ZEEP group) or with administration of dioctylsodiumsulfosuccinate (ZEEP-DOSS group), on negative EEP (NEEP group), or with large Vt (26 ml/kg) on PEEP (Hi-Vt group). No change in lung mechanics occurred in the Control group. Relative to the initial period of MV on PEEP, airway resistance increased by 33 +/- 4, 49 +/- 9, 573 +/- 84, and 13 +/- 4%, and quasi-static elastance by 19 +/- 3, 35 +/- 7, 248 +/- 12, and 20 +/- 3% in the ZEEP, NEEP, ZEEP-DOSS, and Hi-Vt groups. Relative to Control, all groups ventilated from low lung volumes exhibited histologic signs of bronchiolar injury, more marked in the NEEP and ZEEP-DOSS groups. Parenchymal and vascular injury occurred in the ZEEP-DOSS and Hi-Vt groups. Pro-inflammatory cytokine concentration in the bronchoalveolar lavage fluid (BALF) was similar in the Control and ZEEP group, but increased in all other groups, and higher in the ZEEP-DOSS and Hi-Vt groups. Interrupter resistance was correlated with indexes of bronchiolar damage, and cytokine levels with vascular-alveolar damage, as indexed by lung wet-to-dry ratio. Hence, protective MV from resting lung volume causes mechanical alterations and small airway injury, but no cytokine release, which seems mainly related to stress-related damage of endothelial-alveolar cells. Enhanced small airway epithelial damage with induced surfactant dysfunction or MV on NEEP can, however, contribute to cytokine production.

Computational Analysis of Microbubble Flows in Bifurcating Airways: Role of Gravity, Inertia, and Surface Tension

“…(7) represents boundary conditions. Equation (5) can be used to rewrite the free-surface boundary components of the right hand side of Eq. (7) as…”

“…This severely compromises gas transport within the lung and results in severe hypoxia and high mortality rates [4]. Although mechanical ventilation is the standard of care for ARDS patients, the mechanical forces generated during ventilation can exacerbate the existing lung injury, a condition referred to as ventilator-induced lung injury [5]. These mechanical forces may include over-distension of lung epithelial cells [6], high trans mural pressures [7], and surface tension forces during cyclic air way reopening [8,9].…”

“…These mechanical forces may include over-distension of lung epithelial cells [6], high trans mural pressures [7], and surface tension forces during cyclic air way reopening [8,9]. In addition to causing cell necrosis and barrier disruption, these mechanical forces can also activate proinflammatory signaling [5,10], Although recent improvements in ventilation strategies such as low tidal volume ventilation have reduced mortality rates, ARDS currently causes the same number of deaths in the US as breast cancer and prostate cancer combined [11] and developing improved ventilator strategies is a major pub lic health challenge.…”

Simvastatin Treatment Modulates Mechanically-Induced Injury and Inflammation in Respiratory Epithelial Cells

“…However, it is not known if Simvastatin can mitigate cellular injury and inflammation during low tidal volume ventilation. At low lung volumes, the cyclic closure and reopening of fluid-airways results in significant cellular injury and barrier disruption [6, 7]. In addition, ventilation at higher pressures has also been shown to elicit a pro-inflammatory response both in-vivo [12] and in-vitro [13, 14].…”

“…Clinical trials [5] have demonstrated that this type of lung injury, known as volutrauma, can be prevented by using low tidal volumes protocols. Unfortunately, low volume ventilation can also cause significant lung injury and inflammation [6, 7] where the cyclic closure and reopening of fluid filled airways generates dynamic air-liquid interfacial stresses which can cause significant barrier disruption and plasma membrane rupture [8, 9]. Although elevated positive end expiratory pressure (PEEP) protocols have been used in an attempt to prevent this injury, known as atelectrauma, clinical trials have not definitively established that higher PEEP ventilation reduces lung injury [10, 11].…”