Browsing by Subject "shear stress"

High shear stresses and shear rates in left ventricular assist devices (LVADs) make endothelialization of the LVAD difficult and likely contribute to cleavage of large von Willebrand factor multimers and resulting bleeding problems in patients. To better understand shear in a centrifugal LVAD, flow was simulated using finite volume and computational fluid dynamics (CFD) analysis. The k-ω model simulated turbulence and sliding meshes were used to model the movement of the impeller. CFD results showed high-shear backflows in the radial gap between the impeller and the volute wall, but residence times in this region were under 5ms. It is unclear if this is sufficient to cleave VWF, and more study is necessary to determine if other areas in the LVAD have potential for VWF cleavage. Although the walls near the outlet experience low shear stress and may be good candidates for endothelialization, shear stresses above 20-30Pa on all other walls of the pump make the possibility of endothelial cell growth elsewhere in the LVAD unlikely. An LVAD designed specifically to have low shear may be a better candidate for endothelialization.

The adaptive response of vascular endothelial cells to shear stress alteration induced by global hemodynamic changes is an essential component of normal endothelial physiology in vivo; and an understanding of the transient regulation of endothelial phenotype during adaptation will advance our understanding of endothelial biology and yield new insights into the mechanism of atherogenesis. The objective of this study was to characterize the adaptive response of arterial endothelial cells to acute increases in shear stress magnitude and frequency in well-defined in vitro settings. Porcine endothelial cells were preconditioned by a basal level shear stress of ±15dynes/cm^2 at 1 Hz for 24 hours, and an acute increase in shear stress magnitude (30 ±15 dynes/cm^2) or frequency (2 Hz) was then applied. Endothelial permeability to bovine serum albumin was measured and gene expression profiling was performed using microarrays at multiple time points during a period of 6 hours after the shear stress alteration. The instantaneous endothelial permeability was found to increase rapidly in response to the acute increase in shear stress magnitude. Endothelial permeability nearly doubled after 40 minutes exposure to the elevated shear magnitude, and then decreased gradually. However, less dependency of endothelial permeability on shear stress frequency was observed. Endothelial permeability increased slowly from 120 minutes to 6 hours after exposure to the elevated shear frequency, but the increase was not statistically significant and was relatively small (1.2 fold increase at 6 hours). The transcriptomics studies identified 86 genes that were sensitive to the elevated shear magnitude and 37 genes sensitive to the elevated frequency. A significant number of the identified genes are previously unknown as sensitive to shear stress. The acute increase in shear magnitude promoted the expression of a group of anti-inflammatory and anti-oxidative genes; while the acute increase in shear frequency upregulated a set of cell-cycle regulating genes and angiogenesis genes. The adaptive response of global gene expression profile to the elevated shear magnitude is found to be triphasic, consisting of an induction period, an early adaptive response (ca. 45 minutes) and a late remodeling response. However, no apparent temporal regulation pattern of global gene expression was found during the adaptation to the elevated shear frequency. The results from this dissertation suggest that endothelial cells exhibit a specific phenotype during the adaptive response to changes in shear stress; and the transient phenotype is different than that of fully-adapted endothelial cells and may alter arterial atherosusceptibility.