A Micro-Delivery Approach for Studying Microvascular Responses to Localized Oxygen Delivery

BACKGROUND: In vivo video microscopy has been used to study blood flow regulation as a function of varying oxygen concentration in microcirculatory networks. However, previous studies have measured the collective response of stimulating large areas of the microvascular network at the tissue surface. OBJECTIVE: We aimed to limit the area being stimulated by controlling oxygen availability to highly localized regions of the microvascular bed within intact muscle. DESIGN AND METHOD: Gas of varying O(2) levels was delivered to specific locations on the surface of the Extensor Digitorum Longus muscle of rat through a set of micro-outlets (100 μm diameter) patterned in ultrathin glass using state-of-the-art microfabrication techniques. O(2) levels were oscillated and digitized video sequences were processed for changes in capillary hemodynamics and erythrocyte O(2) saturation. RESULTS AND CONCLUSIONS: Oxygen saturations in capillaries positioned directly above the micro-outlets were closely associated with the controlled local O(2) oscillations. Radial diffusion from the micro-outlet is limited to ~75 μm from the center as predicted by computational modeling and as measured in vivo. These results delineate a key step in the design of a novel micro-delivery device for controlled oxygen delivery to the microvasculature to understand the fundamental mechanisms of microvascular regulation of O(2) supply.