Evaluation of Effects of Cyclic Hypoxia on Vascular Permeability Using Microfluidic Device

Ischemic conditioning reportedly improves tissue tolerance to ischemic injury by affecting vascular function through changes in oxygen concentration. However, the detailed mechanisms and effective procedures have not yet been clarified. In this study, we investigated functional changes in the microvascular network and underlying mechanisms, focusing on the generation of reactive oxygen species (ROS). A microvascular network formed in a microfluidic device was exposed to oxygen concentrations of either 21% or $0.3 \% \mathrm{O}_{2}$, as well as cyclic hypoxic condition ranging between 0.3% and $21 \% \mathrm{O}_{2}$ at $30-\mathrm{min}$ intervals for 3 h. Vascular permeability after cyclic hypoxic condition decreased significantly compared to those under the two constant oxygen conditions. Moreover, ROS generation fluctuated in response to the variation in the oxygen concentration under cyclic hypoxic condition, and remained relatively high. Thus, cyclic hypoxia alters microvascular network function in a manner similar to ischemic conditioning and is associated with sustained ROS generation.