Do Vascular and Extracellular Measurements Consistently Reflect Intracellular pO₂?

Oxygen measurements are routinely made either in the vasculature or in the extracellular fluid surrounding the cells of tissues. Yet, metabolic oxygen availability depends on the pO₂ within the cells, as does the enhancing effect of oxygen on radiotherapy outcomes. This article reports quantitative modeling work examining the effect of cellular plasma membrane composition on tissue permeability, as a window into tissue oxygen gradients. Previous application of the model indicates that lipid-mediated diffusion pathways accelerate oxygen transfer from capillaries to intracellular compartments and that the extent of acceleration is modulated by membrane lipid and protein composition. Here, the effects of broken intercellular junctions and increased gap size between cells in the model are addressed. The conclusion is reached that the pO₂ gradient will likely be consistent among similar, healthy tissues but may increase with increased interstitial fluid fraction and broken intercellular junctions. Therefore, tissue structural changes in tumors and other diseased or damaged tissues may lead to aberrations in permeability that confound interpretation of extracellular oxygen measurements.