[Show abstract][Hide abstract] ABSTRACT: Patients with severe acute lung injury are frequently administered high concentrations of oxygen (>50%) during mechanical ventilation. Long-term exposure to high levels of oxygen can cause lung injury in the absence of mechanical ventilation, but the combination of the two accelerates and increases injury. Hyperoxia causes injury to cells through the generation of excessive reactive oxygen species. However, the precise mechanisms that lead to epithelial injury and the reasons for increased injury caused by mechanical ventilation are not well understood. We hypothesized that alveolar epithelial cells (AECs) may be more susceptible to injury caused by mechanical ventilation if hyperoxia alters the mechanical properties of the cells causing them to resist deformation. To test this hypothesis, we used atomic force microscopy in the indentation mode to measure the mechanical properties of cultured AECs. Exposure of AECs to hyperoxia for 24 to 48 h caused a significant increase in the elastic modulus (a measure of resistance to deformation) of both primary rat type II AECs and a cell line of mouse AECs (MLE-12). Hyperoxia also caused remodeling of both actin and microtubules. The increase in elastic modulus was blocked by treatment with cytochalasin D. Using finite element analysis, we showed that the increase in elastic modulus can lead to increased stress near the cell perimeter in the presence of stretch. We then demonstrated that cyclic stretch of hyperoxia-treated cells caused significant cell detachment. Our results suggest that exposure to hyperoxia causes structural remodeling of AECs that leads to decreased cell deformability.
[Show abstract][Hide abstract] ABSTRACT: Elastography, a non-invasive imaging modality, utilizes mechanical properties of tissue as markers for disease diagnosis or staging. In the case of liver, there have been a number of studies focusing on the relationship between elastic mechanical properties and underlying disease, i.e. fibrosis and cirrhosis. In summary, these studies indicate the feasibility of elastographic tools in detecting liver diseases such as fibrosis and steatosis. There have not been any studies looking at the mechanical properties of the preterm neonate liver to date, which is important, because preterm neonates are at a greater risk for developing liver complications due to their aggressive dietary needs that are met with total parenteral nutrition (TPN). They use of elastography may be less from the use of elastographic tools since the concerns over noise levels in measurements resulting from abdominal wall thickness may be less influential. Therefore, it is necessary to establish basic preterm neonate liver mechanical properties. In this study, we measured the nonlinear (hyperelastic) mechanical properties of livers from preterm pigs that were fed common neaonatal diets, i.e. colostrum, total parenteral nutrition (TPN). 16 neonate pigs survived the feeding regime. Mechanical evaluation of 15 of these neonatal pigs was achieved with the use of uniaxial compression experiments at 0.01 s−1 strain rate. The livers averaging a weight of 34.7±7.0 (SD), were stored in phosphate buffered saline solution at 4°C until experimentation, which occurred within 30 minutes of the animal sacrifice. A minimum of three specimens from each liver was required for the computation of averaged mechanical properties. In addition to mechanical testing samples, blood serum was also obtained from these animals and common chemical parameters for liver health were measured (bilirubin, ALT, AST, HDL, LDL, etc.) Exponential form of the hyperelastic strain energy function, W = b1 exp[b2 (L2 + 2/L-3)], where bi are the material parameters and L is the stretch ratio, was utilized to describe the hyperelastic mechanical behavior of the preterm neonate pig livers. With the use of E = 6b1 b2 , a small-strain regime estimate of the elastic modulus of the neonate liver tissue was also computed. The mean b1 and b2 parameters are determined to be 97.00±44.15(SD) Pa and 1.90±0.28(SD) (n = 71). The mean elastic modulus exhibited an linear dependence on the HDL values obtained from chemical analysis of the blood serum. Moreover, although relatively weak, the ratio of the HDL over LDL also correlated with the elastic modulus. To our knowledge, this is the only study to date that has focused on the mechanical properties of preterm neonatal pigs and its correlation with liver lipid profile in neonates. Future work will focus on correlating this information with histology and then devising multi-scale material characterization approaches that link underlying neonatal liver structure to its overall mechanical properties.
ASME 2010 International Mechanical Engineering Congress and Exposition; 01/2010