scholarly journals Temperature-dependent modulation of regional lymphatic contraction frequency and flow

2017 ◽  
Vol 313 (5) ◽  
pp. H879-H889 ◽  
Author(s):  
Eleonora Solari ◽  
Cristiana Marcozzi ◽  
Daniela Negrini ◽  
Andrea Moriondo

Lymph drainage and propulsion are sustained by an extrinsic mechanism, based on mechanical forces acting from the surrounding tissues against the wall of lymphatic vessels, and by an intrinsic mechanism attributable to active spontaneous contractions of the lymphatic vessel muscle. Despite being heterogeneous, the mechanisms underlying the generation of spontaneous contractions share a common biochemical nature and are thus modulated by temperature. In this study, we challenged excised tissues from rat diaphragm and hindpaw, endowed with spontaneously contracting lymphatic vessels, to temperatures from 24°C (hindpaw) or 33°C (diaphragmatic vessels) to 40°C while measuring lymphatic contraction frequency ( fc) and amplitude. Both vessel populations displayed a sigmoidal relationship between fc and temperature, each centered around the average temperature of surrounding tissue (36.7 diaphragmatic and 32.1 hindpaw lymphatics). Although the slope factor of the sigmoidal fit to the fc change of hindpaw vessels was 2.3°C·cycles−1·min−1, a value within the normal range displayed by simple biochemical reactions, the slope factor of the diaphragmatic lymphatics was 0.62°C·cycles−1·min−1, suggesting the added involvement of temperature-sensing mechanisms. Lymph flow calculated as a function of temperature confirmed the relationship observed on fc data alone and showed that none of the two lymphatic vessel populations would be able to adapt to the optimal working temperature of the other tissue district. This poses a novel question whether lymphatic vessels might not adapt their function to accommodate the change if exposed to a surrounding temperature, which is different from their normal condition. NEW & NOTEWORTHY This study demonstrates to what extent lymphatic vessel intrinsic contractility and lymph flow are modulated by temperature and that this modulation is dependent on the body district that the vessels belong to, suggesting a possible functional misbehavior should lymphatic vessels be exposed to a chronically different temperature.

2019 ◽  
Vol 316 (1) ◽  
pp. G217-G227 ◽  
Author(s):  
Olga Y. Gasheva ◽  
Irina Tsoy Nizamutdinova ◽  
Laura Hargrove ◽  
Cassidy Gobbell ◽  
Maria Troyanova-Wood ◽  
...  

This study aimed to establish mechanistic links between the prolonged intake of desloratadine, a common H1 receptor blocker (i.e., antihistamine), and development of obesity and metabolic syndrome. Male Sprague-Dawley rats were treated for 16 wk with desloratadine. We analyzed the dynamics of body weight gain, tissue fat accumulation/density, contractility of isolated mesenteric lymphatic vessels, and levels of blood lipids, glucose, and insulin, together with parameters of liver function. Prolonged intake of desloratadine induced development of an obesity-like phenotype and signs of metabolic syndrome. These alterations in the body included excessive weight gain, increased density of abdominal subcutaneous fat and intracapsular brown fat, high blood triglycerides with an indication of their rerouting toward portal blood, high HDL, high fasting blood glucose with normal fasting and nonfasting insulin levels (insulin resistance), high liver/body weight ratio, and liver steatosis (fatty liver). These changes were associated with dysfunction of mesenteric lymphatic vessels, specifically high lymphatic tone and resistance to flow together with diminished tonic and abolished phasic responses to increases in flow, (i.e., greatly diminished adaptive reserves to respond to postprandial increases in lymph flow). The role of nitric oxide in this flow-dependent adaptation was abolished, with remnants of these responses controlled by lymphatic vessel-derived histamine. Our current data, considered together with reports in the literature, support the notion that millions of the United States population are highly likely affected by underevaluated, lymphatic-related side effects of antihistamines and may develop obesity and metabolic syndrome due to the prolonged intake of this medication. NEW & NOTEWORTHY Prolonged intake of desloratadine induced development of obesity and metabolic syndrome associated with dysfunction of mesenteric lymphatic vessels, high lymphatic tone, and resistance to flow together with greatly diminished adaptive reserves to respond to postprandial increases in lymph flow. Data support the notion that millions of the USA population are highly likely affected by underevaluated, lymphatic-related side effects of antihistamines and may develop obesity and metabolic syndrome due to the prolonged intake of this medication.


Blood ◽  
2016 ◽  
Vol 128 (9) ◽  
pp. 1169-1173 ◽  
Author(s):  
John D. Welsh ◽  
Mark L. Kahn ◽  
Daniel T. Sweet

Abstract Aside from the established role for platelets in regulating hemostasis and thrombosis, recent research has revealed a discrete role for platelets in the separation of the blood and lymphatic vascular systems. Platelets are activated by interaction with lymphatic endothelial cells at the lymphovenous junction, the site in the body where the lymphatic system drains into the blood vascular system, resulting in a platelet plug that, with the lymphovenous valve, prevents blood from entering the lymphatic circulation. This process, known as “lymphovenous hemostasis,” is mediated by activation of platelet CLEC-2 receptors by the transmembrane ligand podoplanin expressed by lymphatic endothelial cells. Lymphovenous hemostasis is required for normal lymph flow, and mice deficient in lymphovenous hemostasis exhibit lymphedema and sometimes chylothorax phenotypes indicative of lymphatic insufficiency. Unexpectedly, the loss of lymph flow in these mice causes defects in maturation of collecting lymphatic vessels and lymphatic valve formation, uncovering an important role for fluid flow in driving endothelial cell signaling during development of collecting lymphatics. This article summarizes the current understanding of lymphovenous hemostasis and its effect on lymphatic vessel maturation and synthesizes the outstanding questions in the field, with relationship to human disease.


2020 ◽  
Vol 18 (2) ◽  
pp. 146-155 ◽  
Author(s):  
Eleonora Solari ◽  
Cristiana Marcozzi ◽  
Barbara Bartolini ◽  
Manuela Viola ◽  
Daniela Negrini ◽  
...  

1991 ◽  
Vol 260 (1) ◽  
pp. H1-H5
Author(s):  
J. M. Dabney ◽  
M. J. Buehn ◽  
D. E. Dobbins

Prostaglandins may contribute to the control of lymph flow by affecting lymphatic vessel contractility. We measured the pressure in perfused prenodal lymphatic vessel in the paw of the anesthetized dog as affected by administration of prostaglandins E1, E2, F2 alpha or arachidonic acid. The forelimb was perfused at constant flow with blood obtained from a femoral artery. Systemic arterial, central venous, and forelimb vascular pressures were measured. When added to the lymphatic perfusate, all of the prostaglandins and arachidonic acid caused constriction of lymphatic vessels. Perfusion of prenodal lymphatics separated from downstream nodes and vessels showed that this constriction occurred primarily in prenodal vessels. However, only prostaglandin F2 alpha caused lymphatic constriction when infused into the blood to the forelimb. Because prostaglandins are a common component of the lymph leaving an area of tissue damage, these results are compatible with the possibility that prostaglandins, by directly affecting lymphatics, help modulate lymph flow following local injury.


2007 ◽  
Vol 293 (2) ◽  
pp. H1183-H1189 ◽  
Author(s):  
Arun M. Venugopal ◽  
Randolph H. Stewart ◽  
Glen A. Laine ◽  
Ranjeet M. Dongaonkar ◽  
Christopher M. Quick

The lymphatic system returns interstitial fluid to the central venous circulation, in part, by the cyclical contraction of a series of “lymphangion pumps” in a lymphatic vessel. The dynamics of individual lymphangions have been well characterized in vitro; their frequencies and strengths of contraction are sensitive to both preload and afterload. However, lymphangion interaction within a lymphatic vessel has been poorly characterized because it is difficult to experimentally alter properties of individual lymphangions and because the afterload of one lymphangion is coupled to the preload of another. To determine the effects of lymphangion interaction on lymph flow, we adapted an existing mathematical model of a lymphangion (characterizing lymphangion contractility, lymph viscosity, and inertia) to create a new lymphatic vessel model consisting of several lymphangions in series. The lymphatic vessel model was validated with focused experiments on bovine mesenteric lymphatic vessels in vitro. The model was then used to predict changes in lymph flow with different time delays between onset of contraction of adjacent lymphangions (coordinated case) and with different relative lymphangion contraction frequencies (noncoordinated case). Coordination of contraction had little impact on mean flow. Furthermore, orthograde and retrograde propagations of contractile waves had similar effects on flow. Model results explain why neither retrograde propagation of contractile waves nor the lack of electrical continuity between lymphangions adversely impacts flow. Because lymphangion coordination minimally affects mean flow in lymphatic vessels, lymphangions have flexibility to independently adapt to local conditions.


2007 ◽  
Vol 293 (1) ◽  
pp. R200-R208 ◽  
Author(s):  
Joshua K. Meisner ◽  
Randolph H. Stewart ◽  
Glen A. Laine ◽  
Christopher M. Quick

Although behavior of lymphatic vessels is analogous to that of ventricles, which completely relax between contractions, and blood vessels, which maintain a tonic constriction, the mixture of contractile properties can yield behavior unique to lymphatic vessels. In particular, because of their limited refractory period and slow rate of relaxation, lymphatic vessels lack the contractile properties that minimize summation in ventricles. We, therefore, hypothesized that lymphatic vessels transition to a state of summation when lymphatic vessel contraction frequency exceeds a critical value. We used an isovolumic, controlled-flow preparation to compare the time required for full relaxation with the time available to relax during diastole. We measured transmural pressure and diameter on segments of spontaneously contracting bovine mesenteric lymphatic vessels during 10 isovolumic volume steps. We found that beat-to-beat period (frequency−1) decreased with increases in diameter and that total contraction time was constant or slightly increased with diameter. We further found that the convergence of beat-to-beat period and contraction cycle duration predicted a critical transition value, beyond which the vessel does not have time to fully relax. This incomplete relaxation and resulting mechanical summation significantly increase active tension in diastole. Because this transition occurs within a physiological range, contraction summation may represent a fundamental feature of lymphatic vessel function.


2011 ◽  
Vol 301 (5) ◽  
pp. H1828-H1840 ◽  
Author(s):  
Tony J. Akl ◽  
Takashi Nagai ◽  
Gerard L. Coté ◽  
Anatoliy A. Gashev

The objective of study was to evaluate the aging-associated changes, contractile characteristics of mesenteric lymphatic vessels (MLV), and lymph flow in vivo in male 9- and 24-mo-old Fischer-344 rats. Lymphatic diameter, contraction amplitude, contraction frequency, and fractional pump flow, lymph flow velocity, wall shear stress, and minute active wall shear stress load were determined in MLV in vivo before and after Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) application at 100 μM. The active pumping of the aged rat MLV in vivo was found to be severely depleted, predominantly through the aging-associated decrease in lymphatic contractile frequency. Such changes correlate with enlargement of aged MLV, which experienced much lower minute active shear stress load than adult vessels. At the same time, pumping in aged MLV in vivo may be rapidly increased back to levels of adult vessels predominantly through the increase in contraction frequency induced by nitric oxide (NO) elimination. Findings support the idea that in aged tissues surrounding the aged MLV, the additional source of some yet unlinked lymphatic contraction-stimulatory metabolites is counterbalanced or blocked by NO release. The comparative analysis of the control data obtained from experiments with both adult and aged MLV in vivo and from isolated vessel-based studies clearly demonstrated that ex vivo isolated lymphatic vessels exhibit identical contractile characteristics to lymphatic vessels in vivo.


2021 ◽  
Vol 20 (5) ◽  
pp. 53-64
Author(s):  
Ramil R. Amerkhanov ◽  
Radislav R. Amerkhanov

Physical rehabilitation, by the foot method of body systemic mobilization, is a new medical technology. In connection with the current global unstable infectious situation, the need arose again to return to the question of finding and developing a systematic approach of simple and generally available physical methods. Aim. Analyze and evaluate the effect of the method of systemic mobilization of the body with the foot on the immune system of the human body, in order to prevent and rehabilitate post-infectious conditions. Material and methods. The research was carried out in various climatic zones. The procedures were based on the techniques of the first, second and third orders, in the second and third age groups. The first group consisted of patients of the second age group (13-60 years old). The second study group was represented by the third age group (60 years +). Materials of the first age group (up to 13 years old) were not submitted to the analysis. The method of exposure stipulated only the canonical motion direction in the selected sessions, the session lasted within 40-70 minutes, every day, for 10-30 days, taking into account weight, age and chronic diseases. 237 male and female patients’ material was reviewed and analyzed. Results and discussion. The method of systemic mobilization of the body exposed to the foot showed more significant positive results in the second age group - 92.8% and less in the third – 78.6% . To achieve positive results, it took more procedures 4 ± 1.0 in a humid climate compared to a dry one. It has been approved that accelerated blood flow in the main and collateral vessels triggers the activity of the lymphatic system. In the primary lymphoid organs, the hematopoietic function is restored and increased, optimizing lymphopoiesis and the state of lymphodynamics. Techniques of the first order (level) restore the flow of lymph through the superficial lymphatic vessels, collecting and producing outflow of lymph from the skin, subcutaneous tissue, superficial fascia and the surface layer of muscle fibers.Techniques of the second order (level) affect the lymph flow of deep lymphatic vessels, collecting lymph from muscles, joints and bones, producing outflow from deeply located tissues, lymphatic vessels lying along the arteries and veins of the same name, actively anastomosing with a network of superficial lymphatic vessels. Techniques of the III order (level) promote lymph flow through the lymphatic capillaries, from intra- and extra-organ lymphatic vessels, trunks and ducts. These techniques create conditions for accelerating drainage in the thoracic duct, producing an “emptying” effect by a direct physical coercion on the vertebral column, penetrating deeply. Conclusion. This method has statistically confirmed studies that indicate its ability to significantly increase the speed of blood flow in the main and adjacent vessels. The method can be considered as having a positive effect on lymphodynamics, in particular on lymphatic capillaries emanating from intra- and extra organ lymphatic vessels, trunks and ducts. By increasing the transport function of the lymphatic vessels, providing a full blood supply (nutrition) to the primary organs of the lymphatic system, exerting a stimulating effect on the spirally oriented lymphangion myocytes, in a soft and carefully worked out way, the foot method of systemic body mobilization creates optimal conditions for the correction of the immune system. Thus, it is able to protect the internal environment of the human body from foreign agents.


Author(s):  
Samira Jamalian ◽  
Christopher D. Bertram ◽  
James E. Moore

One of the primary functions of the lymphatic system is maintaining fluid and protein balance in the body. The system holds this balance by collecting about four liters of fluid every day from the interstitial space and returning it back to the subclavian vein. In contrast to the blood circulation system that relies on the heart for pumping, there is no central pump in the lymphatic system. Thus, the transport of viscous fluid against gravity and pressure difference occurs by recruiting extrinsic and intrinsic pumping mechanisms. Extrinsic pumping is the transport of lymph due to the movements outside the lymphatic vessel such as the pulse in blood vessels, whereas the intrinsic pumping is transport of lymph by contraction of lymphatic muscle cells embedded in the walls of lymphatic vessels. Similar to the veins, the bi-leaflet valves throughout the lymphatic network prevent backflow. Lymphatic valves are biased open and allow for small amounts of back flow before they completely shut.


2020 ◽  
Vol 319 (6) ◽  
pp. F1027-F1036
Author(s):  
Elaine L. Shelton ◽  
Hai-Chun Yang ◽  
Jianyong Zhong ◽  
Michele M. Salzman ◽  
Valentina Kon

Similar to other organs, renal lymphatics remove excess fluid, solutes, and macromolecules from the renal interstitium. Given the kidney’s unique role in maintaining body fluid homeostasis, renal lymphatics may be critical in this process. However, little is known regarding the pathways involved in renal lymphatic vessel function, and there are no studies on the effects of drugs targeting impaired interstitial clearance, such as diuretics. Using pressure myography, we showed that renal lymphatic collecting vessels are sensitive to changes in transmural pressure and have an optimal range of effective pumping. In addition, they are responsive to vasoactive factors known to regulate tone in other lymphatic vessels including prostaglandin E2 and nitric oxide, and their spontaneous contractility requires Ca2+ and Cl−. We also demonstrated that Na+-K+-2Cl− cotransporter Nkcc1, but not Nkcc2, is expressed in extrarenal lymphatic vessels. Furosemide, a loop diuretic that inhibits Na+-K+-2Cl− cotransporters, induced a dose-dependent dilation in lymphatic vessels and decreased the magnitude and frequency of spontaneous contractions, thereby reducing the ability of these vessels to propel lymph. Ethacrynic acid, another loop diuretic, had no effect on vessel tone. These data represent a significant step forward in our understanding of the mechanisms underlying renal lymphatic vessel function and highlight potential off-target effects of furosemide that may exacerbate fluid accumulation in edema-forming conditions.


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