The overall goal of this research is to elucidate the role of blood rheology as a determinant of microvascular function in health and disease. To this end, techniques of intravital microscopy will be applied to evaluate the extent to which red blood cell (RBC) deformability and aggregation, and white blood cell (WBC) deformability and adhesion to the endothelium, affect the resistance to blood flow in vessels ranging from the true capillaries, to the arterioles and venules which serve them. Quantitative indices of microvascular function will be derived from direct in situ measurements of hemodynamic variables in exteriorized tissues such as the mesentery, omentum and cremaster muscle.
Specific aims are to elucidate the relationship between blood flow and blood coli mechanical properties within individual microvessels, at branch points throughout the microvascular network and regionally throughout the succession of major microvascular divisions. A major emphasis of the research will be to elucidate microvascular function in the low flow state by either mechanical obstruction of the arterial inflow, hemorrhagic hypotension or pharmacological intervention. Specific studies on RBCs will delineate the role of red cell aggregation in the margination of WBCs, regional resistance to blood flow and recovery from prolonged ischemic episodes. Studies on RBC deformability will seek to elucidate the effect of its decrease on the process of capillary recruitment during tissue hypoxia, its effect on regional resistance to flow and on the resistance to flow in single unbranched microvessels. Studies on RBC concentration will aim to elucidate the relationship between average tissue hematocrit, determined by the dynamics of red cell flux through the microvasculature, and the tube hematocrit, obtained by direct measurements in individual microvessels. The role of WBC deformability will be examined as a determinant of WBC adhesion to the endothelium and resistance to flow. Techniques of optical sectioning microscopy will be applied to elucidate the role that irregularities in the microvessel lumen play in affecting the resistance to blood flow. It is anticipated that the results of these studies will provide insight into the role of mechanical and biochemical properties of blood cells in affecting microvascular function and aid development of therapeutic strategies to treat a variety of pathologies such as anemia, polycythemia, the low flow state, shock, inflammation and blood cell disorders, to name a few.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cardiovascular and Renal Study Section (CVB)
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Lin, Michael
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Pennsylvania State University
Biomedical Engineering
Schools of Engineering
University Park
United States
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Lipowsky, Herbert H; Bowers, Daniel T; Banik, Brittany L et al. (2018) Mesenchymal Stem Cell Deformability and Implications for Microvascular Sequestration. Ann Biomed Eng 46:640-654
Lipowsky, Herbert H; Lescanic, Anne (2017) Inhibition of inflammation induced shedding of the endothelial glycocalyx with low molecular weight heparin. Microvasc Res 112:72-78
Lipowsky, Herbert H; Lescanic, Anne; Sah, Rachna (2015) Role of matrix metalloproteases in the kinetics of leukocyte-endothelial adhesion in post-capillary venules. Biorheology 52:433-45
Lipowsky, Herbert H; Lescanic, Anne (2013) Shear-dependent adhesion of leukocytes and lectins to the endothelium and concurrent changes in thickness of the glycocalyx of post-capillary venules in the low-flow state. Microcirculation 20:149-57
Lipowsky, Herbert H (2013) In vivo studies of blood rheology in the microcirculation in an in vitro world: Past, present and future. Biorheology 50:3-16
Lipowsky, Herbert H; Lescanic, Anne (2013) The effect of doxycycline on shedding of the glycocalyx due to reactive oxygen species. Microvasc Res 90:80-5
Lipowsky, Herbert H (2012) The endothelial glycocalyx as a barrier to leukocyte adhesion and its mediation by extracellular proteases. Ann Biomed Eng 40:840-8
Lipowsky, Herbert H; Gao, Lujia; Lescanic, Ann (2011) Shedding of the endothelial glycocalyx in arterioles, capillaries, and venules and its effect on capillary hemodynamics during inflammation. Am J Physiol Heart Circ Physiol 301:H2235-45
Lipowsky, Herbert H; Sah, Rachna; Lescanic, Anne (2011) Relative roles of doxycycline and cation chelation in endothelial glycan shedding and adhesion of leukocytes. Am J Physiol Heart Circ Physiol 300:H415-22
Lipowsky, Herbert H (2011) Protease Activity and the Role of the Endothelial Glycocalyx in Inflammation. Drug Discov Today Dis Models 8:57-62

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