Advisor: Dr. J. Brandon Dixon
Dr. Levi Wood (Georgia Institute of Technology)
Dr. Hanjoong Jo (Georgia Institute of Technology)
Dr. Stanislav Emelianov (Georgia Institute of Technology)
Dr. Michael J. Davis (University of Missouri)
Optimum Mechanomodulation of Lymphatic Vessel Contractility Using Oscillatory Pressure Waveforms
The lymphatic system is a network of vessels and nodes transporting and clearing interstitial fluid, orchestrating the immune response, and facilitating lipid transport. An important component of the lymphatic system are the collecting lymphatic vessels which pump lymph through the body by virtue of their intrinsic contractility. The collecting lymphatic vessels are known to be sensitive to their mechanical microenvironment which dictates their contractility. However, relatively little is known about how collecting lymphatic vessel contractility is modulated by their oscillatory mechanical microenvironment and how this mechanosensitivity is affected by lymphatic injury. It is important to know the limits of the mechanomodulation of lymphatic vessels in both physiological and pathological circumstances, since an aberrant microenvironment is frequently associated with lymphatic dysfunction, such as in the case of lymphedema. The present work investigates the role of the oscillatory microenvironment in lymphatics for modulating collecting lymphatic contractility. The mechanomodulation of isolated collecting lymphatic vessels by oscillatory shear stress was investigated and optimal parameters of stimulation were identified for maximizing lymphatic function. The modulation of lymphatic vessels was also investigated in vivo in response to oscillatory pressure gradients mimicking pressure waveforms during massage. Massage-like waveforms modulated collecting lymphatic vessel contractility, and this modulation was altered by lymphatic injury. Thus the oscillatory microenvironment is shown to be an important regulator of lymphatic contractility and the present work provides clues on how the mechanosensitivity of lymphatics can be harnessed to better understand therapeutic approaches to lymphedema.