The lymphatic system performs many crucial functions in health, gathering approximately 4 liters/day of interstitial fluid and returning it to the venous system. As this fluid is filtered, undesirable elements such as tumor cells and foreign pathogens are normally destroyed in lymph nodes. This system is also part of the primary transport mechanism for the immune system. Lymphedema, a debilitating disease for which there is no known cure, affects a large number of cancer patients who have undergone lymph node dissection as well as trauma victims. The lymphatic system is also the major transport route for metastases of the most deadly cancers. Understanding and modeling the transport of lymph remains a challenge. Much of the pumping work comes from the contraction of lymphatic vessel smooth muscle, with valves preventing backflow. We propose to develop a multi-scale network model of the lymphatic circulation based on a combination of physical laws, material descriptions, and models of active cellular processes. Goals of this iterative model development process are to gain a better understanding of normal lymphatic function as well as multiple diseases.

Public Health Relevance

Narrative The lymphatic system is directly involved in Lymhedema, an incurable condition that affects a large percentage of cancer patients who have undergone surgery. It is also involved in the spread of cancer, serving as the principal route of distribution for cancer metastases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL094269-01A1
Application #
7687313
Study Section
Special Emphasis Panel (ZRG1-BST-E (51))
Program Officer
Larkin, Jennie E
Project Start
2009-09-01
Project End
2013-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$689,101
Indirect Cost
Name
Texas Engineering Experiment Station
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
847205572
City
College Station
State
TX
Country
United States
Zip Code
77845
Bertram, C D; Macaskill, C; Davis, M J et al. (2017) Valve-related modes of pump failure in collecting lymphatics: numerical and experimental investigation. Biomech Model Mechanobiol 16:1987-2003
Jamalian, Samira; Jafarnejad, Mohammad; Zawieja, Scott D et al. (2017) Demonstration and Analysis of the Suction Effect for Pumping Lymph from Tissue Beds at Subatmospheric Pressure. Sci Rep 7:12080
Bertram, Christopher D; Macaskill, Charlie; Davis, Michael J et al. (2016) Consequences of intravascular lymphatic valve properties: a study of contraction timing in a multi-lymphangion model. Am J Physiol Heart Circ Physiol 310:H847-60
Bertram, C D; Macaskill, C; Moore Jr, J E (2016) Pump function curve shape for a model lymphatic vessel. Med Eng Phys 38:656-663
Margaris, Konstantinos N; Nepiyushchikh, Zhanna; Zawieja, David C et al. (2016) Microparticle image velocimetry approach to flow measurements in isolated contracting lymphatic vessels. J Biomed Opt 21:25002
Jafarnejad, M; Cromer, W E; Kaunas, R R et al. (2015) Measurement of shear stress-mediated intracellular calcium dynamics in human dermal lymphatic endothelial cells. Am J Physiol Heart Circ Physiol 308:H697-706
Cromer, Walter; Wang, Wei; Zawieja, Scott D et al. (2015) Colonic Insult Impairs Lymph Flow, Increases Cellular Content of the Lymph, Alters Local Lymphatic Microenvironment, and Leads to Sustained Inflammation in the Rat Ileum. Inflamm Bowel Dis 21:1553-63
Zolla, Valerio; Nizamutdinova, Irina Tsoy; Scharf, Brian et al. (2015) Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance. Aging Cell 14:582-94
Jafarnejad, Mohammad; Woodruff, Matthew C; Zawieja, David C et al. (2015) Modeling Lymph Flow and Fluid Exchange with Blood Vessels in Lymph Nodes. Lymphat Res Biol 13:234-47
Kornuta, Jeffrey A; Nepiyushchikh, Zhanna; Gasheva, Olga Y et al. (2015) Effects of dynamic shear and transmural pressure on wall shear stress sensitivity in collecting lymphatic vessels. Am J Physiol Regul Integr Comp Physiol 309:R1122-34

Showing the most recent 10 out of 35 publications