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Dynamics of Nitric Oxide Activity are Sufficient and Optimal to Drive Lymphatic Pumping
Author(s) -
Kunert Christian,
Padera Timothy P,
Munn Lance L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.681.1
Subject(s) - lymphatic system , nitric oxide , lymphatic vessel , chemistry , mechanics , interstitial fluid , lymph , materials science , biophysics , biomedical engineering , physics , pathology , engineering , biology , medicine , organic chemistry , cancer , genetics , metastasis
The lymphatic system is critical for maintaining fluid homeostasis and immunosurveillance in tissues, but it malfunctions in many pathologies. Active pumping of fluid by collecting lymphatic vessels is a critical component of lymphatic function, transferring fluid from initial lymphatic beds, but the details of this mechanism are not well understood. Previous work has shown that lymphatic vessels are equipped with one‐way intraluminal valves to maintain unidirectional flow, and that the contraction of collecting lymphatic vessels is effected by nitric oxide (NO). Here we present a computational model that reproduces the relevant dynamics of lymphatic contraction based on known biological principles of nitric oxide combined with fluid dynamics. Shear stresses imparted by the flowing lymph induce nitric oxide locally, which cause a relaxation (dilation) of the vessel wall. The subsequent rapid degradation of NO allows for vessel contraction and fluid movement, which combined with intraluminal valves results in efficient and robust pumping. We hypothesized that cyclic changes in shear stress and the resulting nitric oxide levels are able to produce and sustain pumping in a lymphatic vessel. To test this, we simulated lymphatic pumping using a lattice Boltzmann (LB) approach. The vessel walls consist of moving boundaries affected by a force proportional to the NO concentration and a damped, harmonic restoring potential. The NO decay and diffusion are calculated by a finite difference scheme. Our simulations show that lymphatic pumping is a stable and robust process, able to operate over a range of parameter space. Contributing to this stability is the short lifetime of NO, optimized for efficient, sustained pumping. We also demonstrate how gravity influences the pumping and that no external steering mechanism is needed.