In Vivo and In Vitro Study into Understanding Pathophysiology in Microcirculation

Many clinical studies have reported that abnormal alteration of blood properties can be a radical cause of physiological malfunctions in hemorheological disorders including heart diseases, diabetes mellitus, and malaria. In these pathological conditions, intensified red blood cell (RBC) aggregability, rigidified RBC and anomalous hematocrit levels are commonly found. However, despite the clinical significance of these findings, information on how such rheological changes of blood influence hemodynamics and gas transport in the microcirculation is currently very limited. Thus, this study aims to provide such information through in vivo experiments and computational simulations.

Since cell-free layer (CFL) formation in microvessels has been of great interest as an important hemodynamic parameter in understanding the microcirculatory response to physiological changes, our proposed approaches will focus on revealing physiological and pathophysiological roles of the CFL in the microcirculation. To ascertain its roles, detailed quantitative information on the CFL characteristics in the presence of hemorheological abnormalities will be acquired by pursuing the following specific aims. Firstly, in vivo CFL data will be obtained from small arterioles in the rat cremaster muscle at pathophysiological levels of RBC aggregability, deformability and hematocrit. In addition, with the use of microsensors developed by our lab, oxygen and nitric oxide levels in the tissue will be measured under the physiological and pathophysiological conditions. Finally, numerical models for hemodynamics and gas tranport in the arterioles will be developed to better understand the pathophysiological role of CFL in microcirlculatory functions. The scientific findings obtained in this research will pave the way for a more detailed exploration of blood disorders, possibly leading to development of better diagnostic tools.

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