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...

IntroductionActive force produced in vessels is directly related to smooth muscle length. Length‐tension relationship is important for characterization of vessels in vitro. We here present a length‐tension curve of isolated human thoracic ducts.Materials and methodsThoracic ducts were harvested from 10 patients undergoing esophageal cancer surgery at the department of thoracic and cardiovascular surgery, University Hospital in Aarhus. The vessels were freed from any surrounding tissue and cut into 2 mm long segments and mounted in a wire myograph for isometric recordings.We used a 10 μM noradrenaline in a K‐PSS (123mM K) solution as an activator to produce maximum force.ResultsLength‐tension relationship was determined from non linear regression fits. Fig 1 shows length‐tension relationship from 45 vessel segments from 10 vessels (n=10). The vessels produced an average total and passive tension of 10.79 and 3.19 N/m, equaling a pressure of 65 ± 7 and 20.8 ± 3 mmHg according to Laplace's law.ConclusionWe have shown it is possible to harvest the thoracic duct from humans and perform in vitro experiments. By using a passive normalization procedure we can now quickly determine the diameter which produces maximal active tension. The results are fundamental for our further physiological and pharmacological studies of these vessels.This research was funded by the Danish Research Council