Lymphatic pump-conduit duality: contraction of postnodal lymphatic vessels inhibits passive flow

Abstract

Lymphangions, the segments of lymphatic vessels between valves, exhibit structural characteristics in common with both ventricles and arteries. Although once viewed as passive conduits like arteries, it has become well established that lymphangions can actively pump lymph against an axial pressure gradient from low-pressure tissues to the great veins of the neck. A recently reported mathematical model, based on fundamental principles, predicted that lymphangions can transition from pump to conduit behavior when outlet pressure falls below inlet pressure. In this case, the axial pressure gradient becomes the major source of energy for the propulsion of lymph, despite the presence of cyclical contraction. In fact, flow is augmented when cyclical contractions are abolished. We therefore used an in vitro preparation to confirm these findings and to test the hypothesis that lymphangion contraction inhibits flow when outlet pressure falls below inlet pressure. Bovine postnodal mesenteric lymphatic vessels harvested from an abattoir were subjected to an inlet pressure of 5.0 cmH(2)O and an outlet pressure that decreased from 6.5 to 3.5 cmH(2)O under control conditions, stimulated with U-46619 (a thromboxane analog) and relaxed with calcium-free solution. Under control conditions, lymphatic flow markedly increased as outlet pressure fell below inlet pressure. In this case, the slopes of the flow versus axial pressure gradient increased with calcium-free conditions (61%, n = 8, P = 0.016) and decreased with U-46619 stimulation (21%, n = 5, P = 0.033). Our findings indicate that the stimulation of lymphatic contractility does indeed inhibit lymphatic flow when vessels act like conduits.

Role of RhoA in Regulating the Pump Function of Isolated Lymphatics From Hemorrhagic Shock Rats

“…It is also important to note that the spasticity effect of control lymphatics can reduce the FPF. These results are in agreement with the previous studies of Telinius et al (29) and Quick et al (30).…”

Multiscale Modelling of Lymphatic Drainage

“…In terms of this modelling, lymph vessels differ from arteries in one very important respect; whilst arterial walls are compliant they are also passive, so the response of the system can be modelled by finding suitable fixed values for L, C and R. Lymphangion walls are actively contractile, contributing to the pumping; and in fact the determination and modelling of this is a significant part of modelling the system as a whole. Venugopal, Quick and collaborators [34,35,[55][56][57] developed a more sophisticated lumped parameter representation of the lymph system using the circuit given in Fig. 7 with the parameters being time-varying.…”

“…This lumped-parameter approach has proved very successful, allowing investigation of individual pumping behaviour [35], for example demonstrating that whilst lymphatic pumping action is beneficial under normal (positive) pressure gradients, it is counterproductive for reverse (negative) gradients. Such reverse gradients occur for cases of edema, external compression or limb elevation, where the interstitial fluid pressure is artificially raised, leading to the permanent opening of the lymphangion valves and the lymphangion acting as a simple conduit [34]. It has also allowed the investigation of the effect of coordination of pumping between successive lymphangions in series [56].…”

Mesenteric lymphatic vessels adapt to mesenteric venous hypertension by becoming weaker pumps

“…Three days are not sufficient for development of new lymphatic vessels (i.e., lymphangiogenesis) (6,47). Although it is possible that interstitial fluid pressure may rise so high that lymphatic pumping is no longer necessary to transport lymph (39,41), weakening of lymphatic pumping (specifically decreased ability to develop active tension) may be responsible for delayed edema resolution following normalization of the edemagenic insult.…”