Human thoracic duct in vitro: diameter-tension properties, spontaneous and evoked contractile activity

Abstract

The current study characterizes the mechanical properties of the human thoracic duct and demonstrates a role for adrenoceptors, thromboxane, and endothelin receptors in human lymph vessel function. With ethical permission and informed consent, portions of the thoracic duct (2-5 cm) were resected and retrieved at T7-T9 during esophageal and cardia cancer surgery. Ring segments (2 mm long) were mounted in a myograph for isometric tension (N/m) measurement. The diameter-tension relationship was established using ducts from 10 individuals. Peak active tension of 6.24 Ϯ 0.75 N/m was observed with a corresponding passive tension of 3.11 Ϯ 0.67 N/m and average internal diameter of 2.21 mm. The equivalent active and passive transmural pressures by LaPlace's law were 47.3 Ϯ 4.7 and 20.6 Ϯ 3.2 mmHg, respectively. Subsequently, pharmacology was performed on rings from 15 ducts that were normalized by stretching them until an equivalent pressure of 21 mmHg was calculable from the wall tension. At low concentrations, norepinephrine, endothelin-1, and the thromboxane-A2 analog U-46619 evoked phasic contractions (analogous to lymphatic pumping), whereas at higher contractions they induced tonic activity (maximum tension values of 4.46 Ϯ 0.63, 5.90 Ϯ 1.4, and 6.78 Ϯ 1.4 N/m, respectively). Spontaneous activity was observed in 44% of ducts while 51% of all the segments produced phasic contractions after agonist application. Acetylcholine and bradykinin relaxed norepinephrine preconstrictions by ϳ20% and ϳ40%, respectively. These results demonstrate that the human thoracic duct can develop wall tensions that permit contractility to be maintained across a wide range of transmural pressures and that isolated ducts contract in response to important vasoactive agents. lymphatic system; lymph pump; lymphangion; lymphatic smooth muscle THE EXCESS FLUID AND PROTEIN of the interstitial spaces in almost all tissues of the body are collected and removed by the lymphatic system. The lymphatic capillaries converge into larger collecting lymphatics, and, ultimately, these terminate into large transport vessels, which return lymph to the blood circulation. The lymphatic system lacks a central pump to drive the transport of lymph. Instead, it is generally accepted that the lymphatic smooth muscle cells (LSMCs) in the collecting and transporting lymphatic vessel wall are responsible for propelling lymph forward by intrinsic contractions. The lymphatic vessels responsible for pumping are comprised of multiple contractile segments separated by unidirectional valves to prevent backflow, termed a lymphangion, and each lymphangion performs much like a cardiac ventricle to provide unidirectional pumping. The contractile part of the lymphatic vasculature can thus be likened to a system of ventricles in series (27). The thoracic duct is the largest lymphatic vessel in the human body. Under normal conditions (i.e., in healthy individuals), it is a low-flow system that drains up to 1 ml/min to the venous circulation (30,44). The volume and flow of lymph a...

The contribution of K+ channels to human thoracic duct contractility

“…It is important to note that the thoracic ducts came from aged patients with a malignancy; thus, local and systemic changes as potential influencers of our results cannot be excluded. Tissue harvest was performed as previously described (5,25,26). In brief, a separate tissue block at level T7-T9 was removed and immediately placed in cold (4°C) physiological saline solution (PSS), and the thoracic duct was subsequently dissected free from the surrounding connective tissue and fat under a stereomicroscope.…”

“…Each ring segment was normalized by setting them to an internal diameter where the wall tension was equivalent to a transmural pressure of 21 mmHg [the value at which vessels were determined to produce peak active tension (26)] using the DMT Normalization module for Chart software.…”

Identification of Interstitial Cajal-Like Cells in the Human Thoracic Duct

“…water-immersion objective (LD C-Apocromat, N.A.1.1). SMCs were examined by staining with rhodamine-labeled phalloidin, as described previously [Telinius et al, 2010]. In all instances, scanning was initiated from the luminal side.…”

“…Given the volume of chyle they have to transport postprandially, the hydrostatic pressure gradient created by gravity and the need to develop pressure higher than the venous pressure in order to empty into the venous system, the TD lymphangions represent those most likely to generate the strongest propulsion in the human lymphatic system. Indeed, our previous functional study of isolated human TD demonstrates that this vessel can generate contractile tone that would result in an equivalent transmural pressure of approximately 70 mm Hg [Telinius et al, 2010].…”

“…Spontaneous activity independent of heart or respiratory activity, nervous or humoral inputs, or flow and pressure changes has also been observed in animal TD [Reddy and Staub, 1981;Onizuka et al, 1997;Moffatt and Cocks, 2004] and in human TD in situ under anesthesia [Kinmonth and Taylor, 1956;Kinmonth and Sharpey-Schafer, 1959;Edwards et al, 1965] and ex vivo [Sjoberg and Steen, 1991;Telinius et al, 2010]. The cellular mechanism responsible for the spontaneous and autoregulatory activity of the lymphatic vasculature has been debated since the very first experimental observations of this activity in animals.…”