Measurement and Analysis of the Dynamics of Erythrocyte Oxygen‐Dependent ATP Release

Abstract

Erythrocytes play a key role in the distribution of oxygen (O2) supply in the microvasculature through the oxygen saturation (SO2)‐dependent release of adenosine triphosphate (ATP). Previous studies address the magnitude of ATP release, however, little attention is given to the dynamics, which are crucial to understanding this regulatory system. Our goal is to characterize the dynamics of SO2‐dependent ATP release as it applies to O2 mediated blood flow regulation. Previously, we developed a computational model of a device capable of measuring the dynamics of ATP release (Sove PLOS 2013). In the present study we have modified the model to match our current prototype that utilizes a new fabrication approach of embedding a polymethyl methacrylate (PMMA) O2 impermeable barrier with a window for O2 exchange, in a polydimethylsiloxane (PDMS) O2 permeable layer. The model predicts how the PDMS exchange surface between the erythrocyte and gas channels affects the rate of O2 saturation decrease; thus making it possible to optimize the design of the device and to define appropriate hematocrit and flow conditions for in vitro studies. The model predicts that the PDMS layer thickness causes a decrease in the rate of SO2 decrease, and that low hematocrit results in larger SO2 decrease in a quasi‐linear relationship (slope ‐0.12). Despite the predicted SO2 decrease, ATP release is less due to the decreased number of erythrocytes. Our model shows that decreasing flow rate decreases the SO2, which results in a decrease in spatially derived resolution of ATP release time. The model of the microfluidic device aids in the design of future prototypes, facilitates the analysis of experimental results and provides a means to extract information from in vitro studies that cannot be measured directly.