Lymphatic valve lock in response to modest gravitational loads: a contributing mechanism to peripheral lymphedema?

Lymphedematous limbs often have an uninterrupted column of lymph that implies an underlying contractile dysfunction of collecting lymphatic vessels. To test this idea, single lymphangions were isolated, cannulated and connected to a servo system to control input (Pin) and output (Pout) pressures. Intraluminal pressure was measured with vessel diameter and valve position. As Pout and Pin were slowly raised in parallel, with Pout > Pin to mimic conditions in a dependent extremity during development of edema, the vessel progressively distended and the output valve would appear to suddenly “lock” into the open position. Valve lock appeared to result from the interaction of three factors: tone, pump strength, and valve leaflet stiffness. In multiple lymphangion segments, valve lock occurred in the weakest lymphangion and progressed to its neighbors as pressure rose. Surprisingly, valve lock was reversible if tone was enhanced using a contractile agonist, even at elevated Pout levels. We propose that pump strength, valve leaflet stiffness and tone normally interact to minimize the likelihood of valve lock, which reflects an inherent susceptibility of the valves that can be triggered by modest pressure or volume overload. Once valve lock occurs, it would exacerbate edema by creating an uninterrupted lymph column that transmits a pathological pressure level back to the lymphatic capillaries.