Mechanisms of surface-tension-induced epithelial cell damage in a model of pulmonary airway reopening

Abstract

Airway collapse and reopening due to mechanical ventilation exerts mechanical stress on airway walls and injures surfactant-compromised lungs. The reopening of a collapsed airway was modeled experimentally and computationally by the progression of a semi-infinite bubble in a narrow fluid-occluded channel. The extent of injury caused by bubble progression to pulmonary epithelial cells lining the channel was evaluated. Counterintuitively, cell damage increased with decreasing opening velocity. The presence of pulmonary surfactant, Infasurf, completely abated the injury. These results support the hypotheses that mechanical stresses associated with airway reopening injure pulmonary epithelial cells and that pulmonary surfactant protects the epithelium from this injury. Computational simulations identified the magnitudes of components of the stress cycle associated with airway reopening (shear stress, pressure, shear stress gradient, or pressure gradient) that may be injurious to the epithelial cells. By comparing these magnitudes to the observed damage, we conclude that the steep pressure gradient near the bubble front was the most likely cause of the observed cellular damage.

The pulsatile propagation of a finger of air within a fluid-occluded cylindrical tube

“…We have also found that for Ca Ω < 10Ca M the bubble tip pressure drop ΔP tip may be estimated accurately from the pressure measured downstream of the bubble tip when corrections for the pressure drop due to Poiseuille flow are applied. The normal stress gradient at the tube wall (∂τ n /∂z) is discussed in detail, as this is believed to be the primary factor in airway epithelial cell damage (Bilek et al 2003). In the unsteady regime we find that local film-thinning produces high ∂τ n /∂z at low Ca Ω .…”

“…Bilek et al (2003) demonstrated that an increased normal stress gradient ∂τ n /∂z along a channel wall is directly correlated to increased cell mortality. Those studies focused on very small values of Ca (2.7 × 10 −5 ≤ Ca ≤ 6.8 × 10 −4 ), and showed that a decrease in Ca resulted in an increase in ∂τ n /∂z (corresponding to increased cell damage).…”

“…Spatial and Temporal Behavior- Bilek et al (2003) and Kay et al (2004) have demonstrated that the normal stress gradient is the mechanical stimulus that leads to cellular membrane disruption caused by a finger of air passing over epithelial cells in a fluid-filled channel. In this sub-section, we investigate the implications of the temporal and spatial variation of ∂τ n /∂z, which leads to the complex signature described in Figure 12a,c.…”

Pressure induced nucleus DNA fragmentation

“…For example, the cell membrane of the pulmonary epithelial cells could be disrupted by the steep pressure gradient appearing during airway reopening [3,6]. Furthermore, cytoskeletal damage in vitro was demonstrated after the impact of 16 MPa (120000 mmHg) on a human renal carcinoma cell line [4].…”

“…Therefore, it is reasonable to suspect that the pressure changes may influence the vital function of the cell. According the recent studies, pressure fluctuations can induce cell membrane disruption, cytoskeleton disorganization and enzymes inactivation [2][3][4][5][6]. There are also some evidences about the pressure induced fragmentation of DNA isolated from cells [7][8][9].…”