Analysis of pH gradients resulting from mass transport limitations in engineered heart tissue.

Journal Article (Journal Article)

Transport limitations of critical nutrients are a major obstacle in the construction of engineered heart tissues (EHTs), and the importance of oxygen in this regard is well-documented throughout the literature. An indirect effect of cellular hypoxia is the shunt to the less-efficient glycolytic metabolism, which is accompanied by a reduction in extracellular pH. Image analysis of phenol red coloration in an experimental model of EHTs demonstrated pH gradients towards the center of the construct, which were dependent on experimental variables. Based on these observations, a four-species, 2-D diffusion-reaction mathematical model was developed to predict pH in a radial-diffusion model. The mathematical model predicted lethal values of pH (<6.5) in EHTs comprised of a nominal cell density of 10(6) cells/cm(3). pH predictions were moderately dependent on O(2) concentration, and strongly dependent on cell density, CO(2) concentration, and diffusion path length. It can be concluded from this study that hypoxia-induced acidosis is an important element in the mass transport problem, and future experiments measuring pH with more sensitive methods is expected to further elucidate the extent of this effect.

Full Text

Duke Authors

Cited Authors

  • Brown, DA; Maclellan, WR; Wu, BM; Beygui, RE

Published Date

  • November 2007

Published In

Volume / Issue

  • 35 / 11

Start / End Page

  • 1885 - 1897

PubMed ID

  • 17680364

International Standard Serial Number (ISSN)

  • 0090-6964

Digital Object Identifier (DOI)

  • 10.1007/s10439-007-9360-4


  • eng

Conference Location

  • United States