Electronic Thesis and Dissertation Repository


Doctor of Philosophy


Biomedical Engineering


Professor Jun Yang

2nd Supervisor

Professor Christopher G. Ellis

Joint Supervisor


Since erythrocytes release the vasodilator adenosine triphosphate (ATP) in an oxygen (O2) dependent manner, erythrocytes are proposed to play a central role in O2 regulation. This ATP signaling mechanism is proposed to be most efficient in the capillaries due to the short diffusion distance to the electrically coupled endothelium which communicates directly with arterioles. We hypothesize that capillaries are able to signal upstream arterioles for changes in erythrocyte supply rate in response to changes in capillary erythrocyte O2 saturation (SO2)through SO2-dependent ATP signaling. To test this hypothesis, we have developed a micro-delivery system for controlling the O2 availability to highly localized regions of the micro-vascular bed within intact tissue (rat Extensor Digitorum Longus). This approach allows for altering the erythrocyte SO2 level in selected capillaries while simultaneously recording blood flow changes using in vivo video microscopy (IVVM). Three designs for the O2 exchange outlet were tested. Gas with varying levels of O2 was directly transported to specific locations on the surface of the muscle through a circular micro-outlet (~100 μm in diameter), a square micro-slit (200 μm x 200 μm), or a rectangular micro-slit (1000 μm wide x 200 μm long) patterned in ultrathin glass/plastic sheet using state-of-the-art microfabrication techniques. Video sequences captured during oscillating O2 levels were processed for changes in capillary hemodynamic parameters and erythrocyte SO2. Our results indicated that a sufficient number of capillaries need to be affected by local O2 perturbations in order to elicit micro-vascular responses.. Although erythrocyte SO2 can be measured in single capillaries flowing over an O2 micro-outlet down to 100 μm in diameter, at least 3-4 capillaries needed to be stimulated within a branching capillary network in order to induce conducted micro-vascular responses. Since the measured supply rate responses show strong linear correlation with capillary erythrocyte SO2, the responses are suggested to be linked to an SO2-dependent signaling mechanism by the erythrocyte, which further supports our hypothesis. Based on the results, we have successfully designed a novel micro-delivery device for localized O2 exchange at the microvasculature to understand fundamental mechanisms of micro-vascular regulation of O2 supply.