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 #
5R01HL094269-04
Application #
8317718
Study Section
Special Emphasis Panel (ZRG1-BST-E (51))
Program Officer
Larkin, Jennie E
Project Start
2009-09-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$662,265
Indirect Cost
$194,025
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
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Gashev, Anatoliy A; Chatterjee, Victor (2013) Aged lymphatic contractility: recent answers and new questions. Lymphat Res Biol 11:2-13
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Gashev, Anatoliy A; Zhang, Rong-Zhen; Muthuchamy, Mariappan et al. (2012) Regional heterogeneity of length-tension relationships in rat lymph vessels. Lymphat Res Biol 10:14-9
Thangaswamy, Sangeetha; Bridenbaugh, Eric A; Gashev, Anatoliy A (2012) Evidence of increased oxidative stress in aged mesenteric lymphatic vessels. Lymphat Res Biol 10:53-62
Akl, Tony J; Nagai, Takashi; Cote, Gerard L et al. (2011) Mesenteric lymph flow in adult and aged rats. Am J Physiol Heart Circ Physiol 301:H1828-40
Davis, Michael J; Rahbar, Elaheh; Gashev, Anatoliy A et al. (2011) Determinants of valve gating in collecting lymphatic vessels from rat mesentery. Am J Physiol Heart Circ Physiol 301:H48-60

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