Intrinsic pump-conduit behavior of lymphangions

Abstract

Lymphangions, segments of lymphatic vessels bounded by valves, have characteristics of both ventricles and arteries. They can act primarily like pumps when actively transporting lymph against a pressure gradient. They also can act as conduit vessels when passively transporting lymph down a pressure gradient. This duality has implications for clinical treatment of several types of edema, since the strategy to optimize lymph flow may depend on whether it is most beneficial for lymphangions to act as pumps or conduits. To address this duality, we employed a simple computational model of a contracting lymphangion, predicted the flows at both positive and negative axial pressure gradients, and validated the results with in vitro experiments on bovine mesenteric vessels. This model illustrates that contraction increases flow for normal axial pressure gradients. With edema, limb elevation, or external compression, however, the pressure gradient might reverse, and lymph may flow passively down a pressure gradient. In such cases, the valves may be forced open during the entire contraction cycle. The vessel thus acts as a conduit, and contraction has the effect of increasing resistance to passive flow, thus inhibiting flow rather than promoting it. This analysis may explain a possible physiological benefit of the observed flow-mediated inhibition of the lymphatic pump at high flow rates.

Modulation of lymphatic muscle contractility by the neuropeptide substance P

“…The effect of SP on tone may be important pathologically because, at very high intraluminal pressures associated with chronic edema (3,14,20,37,48), the normal uphill pressure gradient (16,17) may be reversed and collecting lymphatics may switch, over a prolonged period of time, from functioning as pumps to serving as conduits (12,38). Although this effect might be advantageous to interstitial fluid balance at moderately elevated interstitial and lymphatic pressures, excessive basal tone development promoted by SP could be disadvantageous by increasing the resistance of the collecting lymphatic conduits and potentially exacerbating the edema.…”

“…1 and 8, tone could potentially be quite pronounced at high SP doses, if such concentrations are ever achieved in vivo, e.g., during edema. With the assumption that SP release is graded in proportion to the severity of edema (which has not yet been tested), a logical conclusion is that SP receptor blockers would exacerbate mild edema (by interfering with SP-induced pump enhancement) but would partially alleviate severe edema [by blocking the SP-induced constriction of passive lymphatic conduits (38)]. Whether this prediction is correct remains to be determined.…”

Anatomy and roles of lymphatics in inflammatory diseases

“…Simultaneously, lymphatics exhibit tonic contraction resembling myogenic responses in arterioles, which regulate lymphatic vessel diameter, vessel compliance and resistance. [80][81][82] Although phasic lymphatic muscle contraction within lymphangions is responsible for the propulsive lymph flow into downstream segments, tonic contraction is believed to participate in maintaining the vascular tone and integrity. Phasic contraction of lymphangions in response to distension is the primary pump mechanism, which ejects lymph into downstream collecting lymphatics.…”

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

“…These capillaries drain into precollecting and collecting vessels that have continuous, "zipper-like" interendothelial junctions [30] and are surrounded by smooth muscle. Collecting vessels are organized into contractile segments called lymphangions, separated by bileaflet valves, that create the driving force for unidirectional lymph propulsion [30,31,[34][35][36]. Collecting lymphatic vessels that carry lymph to and from the lymph nodes are referred to as afferent and efferent lymphatic vessels, respectively.…”