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PubMed2004

The lymphatic vascular system: secondary or primary?

It has generally been accepted that the blood vascular system is primary and the lymphatic vascular system secondary. Diseases of the blood vascular system are the leading cause for mortality and morbidity in developed nations. In contrast, lymphedema is seldom life-threatening and can generally be well-managed by combined physiotherapy. During ontogeny, the blood vessels and the heart develop much earlier than the lymphatic vessels. However, there is growing evidence that the first vascular system occurring during ontogeny and phylogeny has lymphatic functions. Defense mechanisms are crucial for all organisms irrespective of their size. Macrophages precede the emergence of erythrocytes during ontogeny, and their circulation in the hemolymphatic (more accurately, lymphohematic) system of insects, which do not possess erythrocytes, shows that the lymphatic function is primary whereas the nutritive function is secondary, needed only in larger organisms. In molluscs and arthropods, which have an open vascular system, hemocyanin has both oxygen transporting and defense functions. In vertebrates, the early blood vessels have structural characteristics of lymphatics and express the lymphendothelial receptor flt-4 (Vascular Endothelial Growth Factor Receptor-3). Later, flt-4 becomes restricted to the definitive lymphatics, which are either formed from the primary vessels or from mesodermal lymphangioblasts. The primary lymphatic function has become overruled by the nutritive function in blood vessels of larger animals. The circular movement of cells is driven by a blood heart, which, however, is not an unique organ. Lymph hearts are present in lower vertebrates, still develop transiently in birds, and are vestigial in the contractile lymphangion which "circulates" immune cells. We conclude that the definitive lymphatics are perhaps secondary in mammals, but the blood vascular system seems to develop on the basis of an ancestral lymphatic system with lymph hearts.

Animals↗
PubMedDate not supplied

[Distribution of the lymph vessels in the mouse heart. A light and electron microscopic study (author's transl)].

The lymphatic system in normal mouse heart was investigated by light and electron microscopy. Lymph vessels were only demonstrated in the subepicardial layer and the outer half of the myocardium. Here above all they were situated in close vicinity to arteries and thin-walled veins, rarely separated in the interstitial space, never in the subendocardial layer of the left ventricular wall. The myocardium contains only 2 lymph vessels per mm2. By means of electron microscopy all lymph vessels were regarded as lymph capillaries. Their ultrastructure is described in detail. This investigation shows that lymph vessels in normal heart are rarer than supposeed till now. It is possible that most of the ultrafiltrated fluid is drained by the cardiac venous system, while the lymphatic system only has to transport a small amount of protein-rich fluid.

Animals↗
PubMedDate not supplied

Role of the lymphatic circulatory system in shock.

That the lymphatic vessel participates in the regulation of interstitial dynamics through its ability to contract and propel fluid and protein from the extravascular tissues back to the bloodstream has not been fully appreciated. The "lymph pump" appears to be regulated by local physiologic forces as well as neurogenic and humoral factors. We have assessed the effects of hemorrhage and endotoxin on the ability of the lymph vessel to propel fluid in sheep using a model system that permits the quantitation of lymphatic pumping in vivo without the complication of variable lymph inputs. A major blood loss was found to enhance lymphatic contractile activity and fluid pumping. Considering the large reservoir of fluid and protein in the interstitium and lymph, we speculate that stimulation of the "lymph pump" after hemorrhage might help to re-expand the vascular space. On the other hand, the intravenous administration of endotoxin inhibited lymphatic pumping, suggesting that impaired lymph propulsion in sepsis may contribute to edema by reducing the ability of the lymphatic vessel to remove extravasated protein from the tissues.

Animals↗
PubMedDate not supplied

Effects of hypervolemia and hypovolemia on cardiac and posterior lymph heart function in the toad Bufo marinus (L.).

Cardiac and posterior lymph heart function in the toad Bufo marinus (L.) were measured in response to hemorrhage and both systemic and lymphatic volume loading to evaluate the role of the amphibian lymphatic system in fluid regulation. In every animal, systemic volume loading elicited an initial sharp rise in mean arterial blood pressure, corresponding to an immediate cessation of lymph heart contraction lasting approximately 12 min. This was followed by a short-term decrease in blood pressure, to 36% below normal. While stroke volume and lymph flow for the individual animals increased variably over a 6-h period, mean lymph heart rate and pressure varied little. Lymphatic volume loading elicited only minor changes in blood heart and lymph heart rate. Again, stroke volume and lymph flow increased variably, with the effect lasting about 13 h. Hypovolemia caused a sharp drop in blood pressure and a corresponding rise in blood heart rate. Lymph heart variables changed little, with the exception of rate, which, in some animals, was elevated for approximately 20 min following hemorrhage.

Animals↗
PubMed1994

[Pathology of rheumatoid lung].

In the framework of rheumatic illnesses, the lungs and pleura are often observed to be involved. Dependent on the basic illness in question, conditions of the bronchoalveolar system, vessels, lymphatic system, and pleura that have developed differently inter- and intra-individually can be diagnosed in topo-regionally variable forms and combinations. In the causal pathogenesis, the initial (auto-) immunological alteration of the alveolar septa plays a role. When the monocytes, macrophages, and fibroblasts are activated, as a result of a chronic inflammatory process there is increasing reparative proliferation, which finally leads to the non-specific end stage of irreversible interstitial fibrosis. The incidence and manifestation forms of lung changes show certain differences dependent on the underlying illness (e.g., rheumatoid arthritis, systemic lupus erythematosus, progressive systemic scleroderma, dermatomyositis and polymyositis, Sjögren syndrome, and mixed connective tissue disease). In addition to vasculitis and granulomatosis of the lung, therapy-induced lung changes must also be considered in the differential diagnosis since almost all basic therapeutic agents can cause this type of lung condition. Good knowledge of the parameters from the viewpoint of possible therapeutic measures is indispensable, as is close cooperation between the treating physician and the pathologist.

Arthritis, Rheumatoid↗
PubMed2003

Development and characterization of endothelial cells from rat microlymphatics.

BACKGROUND: The lymphatic endothelium is important to the functioning of the lymphatic system, including lymphatic remodeling, control of vessel tone, and lymphatic movement of fluids, macromolecules, and cells. Many of these events occur principally at the level of the microlymphatics. To evaluate the role of the microlymphatic endothelium, a suitable cultured cell line would be useful. We have developed a technique to isolate and culture endothelial cells from microscopic lymphatics, approximately 100 microm in diameter. METHODS AND RESULTS: To isolate the rat mesenteric lymphatic endothelial cells (RMLEC), the rat was anesthetized and the mesentery carefully exteriorized. A suitable microlymphatic was located and carefully microdissected from the surrounding mesentery. The vessel was carefully cleaned, cannulated, everted, and then incubated on a gelatin-coated plastic culture dish until small patches of cells migrated off of the vessel (3-4 days later.) The explanted vessel was then removed. The remaining cells were cultured and screened for endothelial phenotype. Nonendothelial cells were destroyed. The endothelial nature of the remaining cells was verified by: 1) morphology, 2) uptake of fluorescent acetylated-LDL, 3) staining for von Wille-brand factor, PECAM-1, ecNOS, LYVE-1, VEGFR-3, and 4) essentially negative alpha-vascular smooth muscle actin staining. The defined RMLEC were passed and the profile of adhesion molecules present on the RMLEC was then determined using PCR and immunofluorescence. CONCLUSIONS: We developed and partially characterized a line of cultured microlymphatic endothelium. RMLEC express known endothelial- and lymphatic-specific markers as well as the following adhesion molecules: N-cadherin, E-cadherin, PECAM-1, alpha-catenin, beta-catenin, gamma-catenin, p120, and a variety of integrins.

Actins↗
PubMed1993

Communication between peritoneal cavity and mediastinal lymph nodes demonstrated by Tc-99m albumin nanocolloid intraperitoneal injection.

Lymphatic drainage from the peritoneal cavity to mediastinal lymph nodes has been reported, indicating that abdominal fluid is not immobile. We studied this movement in rats receiving Tc-99m albumin nanocolloid which has smaller particle sizes than does Tc-99m microaggregated albumin colloid used for liver/spleen imaging. The Tc-99m albumin nanocolloid had a radiochemical purity of 99.33%-99.77% with free pertechnetate of 0.23%-0.67%. During pentobarbital anesthesia, thoracoabdominal images were obtained 4-6 hr after intraperitoneal injection of 350 mCi Tc-99m albumin nanocolloid with 5 ml of normal saline. The images showed symmetrical radiotracer localization in the mediastinal lymph nodes. Scintigraphic demonstration of drainage to the mediastinal region from the peritoneal cavity may be explained by flow directly into mediastinum through the lymphatic system, indicating lymphatic patency between the peritoneal cavity and mediastinum. Absence of visualization may indicate lymphatic block. This type of information concerning lymphatic drainage may have clinical impact for a patient with malignant or intractable ascites. The radionuclide technique is easily performed for this assessment.

Animals↗
PubMedDate not supplied

[Role of radioisotopic lymphoscintigraphy in postphlebitic syndrome of the legs].

Post-phlebitis syndrome of the lower limbs is a set of symptoms that follow a state of phlebostasis and phlebolymphostasis with consequent oedema and tissue distress. We submitted 36 patients with post-phlebitis syndrome of the lower limbs to radioisotopic lymphoscintigraphy for the purposes of evaluating the vicariant function of the lymphatic system and the possible role of the lymphatic system in the genesis of dermo-epidermal abnormalities. The average age of the patients was 53.2 years (range: 43-69 years; M:F ratio: 0.50). The control group consisted of 6 healthy subjects. The average duration of the post-phlebitis syndrome in the patients studied was 8.5 years. We excluded from the study patients in whom a central cause was identified as being responsible for the pathogenisis of the oedema of the lower limbs. In addition, patients with obliterant arteriopathy were also excluded. Venous pathology was evaluated first clinically and then investigated by continuous-wave Doppler. As a first step, venous pressure was measured by Doppler phlebomanometry in clino- and orthostatism. All patients underwent radioisotopic lymphoscintigraphy with microcolloids using the Rijke technique. Radioactivity was monitored by means of a computerized gamma-camera. We classified the pathological findings of radioisotopic lymphoscintigraphy as follows: 1) delayed transit; 2) obstacles; 3) star-shaped superficial collateral lymphatic circulations; 4) lymphocoele or cutaneous lakes. A significant difference was detected (p < 0.05) between the pressure values in the post- phlebitis lower limbs and the pressure values in normal subjects. Combining the results of our measurements we recorded delayed transit in 5 patients (69.5%). This latter group included the cases with the severest forms of post-phlebitis syndrome. Therefore, better knowledge of the pathophysiology of the lymphatic system would appear to be useful in order to understand the origin and evolution of oedema of the lower limbs of patients with post-phlebitis syndrome. To this end, radioisotopic lymphoscintigraphy may be useful as a first-level examination in order to evaluate the capacity and efficiency of the lymphatic system.

Adult↗
PubMed1975

Mastomys natalensis as an experimental host for Brugia malaye subperiodic.

Infective larvae of Brugia malayi subperiodic obtained by dissection of infected Aedes togoi were injected subcutaneously into the scrotal region of Mastomys natalensis. From altogether 58 infected male M. natalensis 81% showed consistently or intermittently detectable microfilaraemia, whereas in 19% of the animals no microfilaraemia could be detected at any stage. The mean prepatent period was 136 days; the microfilarial density varied from 1 to 535 per 20 c. mm blood. In those animlas with consistently detectable and in general higher microfilaraemia an average of 13.1 live adult worms were found, against an average of 6.4 adult worms in animals with intermittent detectable and in general lower microfilaraemia. An average of 1.5 worms was found in animals which at no stage showed detectable microfilaraemia. A correlation between worm burden and prepatent period could be observed in the individual groups. From the total of 520 live adult worms recovered at necropsy, 37% were found in the lungs, 29% in the parenchyma of the testes and 34% in the lymphatic system. 47% of live fertile female worms were found in the lymphatic system, whereas the majority, i.e; 52% of infertile female worms were detected in the lungs. In addition, 380 encapsulated dead worms were found, most of them (98%) in the lymphatic system. 61% of a total of 900 live and dead worms were found in the region of the lymphatic system.

Animals↗
PubMed2000

Functional anatomy of lymphatic vessels under the aspect of tumor invasion.

In the human body there are about 800 lymph nodes, of which 300 are located in the head and neck area. The lymphatic system begins with initial finger-shaped lymphatic vessels consisting of valveless lymphatic capillaries and precollectors with valves. The precollectors become collectors and transport the lymph to the so-called lymph stems. These vessels lead into the right and left lymphatic duct and into the jugular trunk of the head and neck region. At the end they join into the blood circulation at the junction point of the jugular and subclavian veins. On the basis of the morphology of the initial lymphatics, these are probably the main port of entry of tumor cells. Investigations demonstrate the active invasion into the lymphatic system of melanoma cells. The preference of melanoma cells to adhere to the extracellular fibronectin of the endothelial cells may be a reason for the privileged invasion of the melanoma cells in the lymphatic system, because the extracellular matrix is not protected by a continuous basal lamina like blood vessels. Based on the directed movement of melanoma cells towards the fiber felt, there might be regulative mechanisms influencing the process of targeted adhesion.

Endothelium, Lymphatic↗
PubMed2001

Evidence for a second valve system in lymphatics: endothelial microvalves.

The mechanism for interstitial fluid uptake into the lymphatics remains speculative and unresolved. A system of intralymphatic valves exists that prevents reflow along the length of the lymphatic channels. However, these valves are not sufficient to provide unidirectional flow at the level of the initial lymphatics. We investigate here the hypothesis that initial lymphatics have a second, separate valve system that permits fluid to enter from the interstitium into the initial lymph channels but prevents escape back out into the tissue. The transport of fluorescent microspheres (0.31 microm) across endothelium of initial lymphatics in rat cremaster muscle was investigated with micropipette manipulation techniques. The results indicate that microspheres can readily pass from the interstitium across the endothelium into the lumen of the initial lymphatics. Once inside the lymphatic lumen, the microspheres cannot be forced out of the lumen even after elevation of the lymphatic pressure by outflow obstruction. Reaspiration of the microspheres inside the lymphatic lumen with a micropipette is blocked by the lymphatic endothelium. This blockade exists whether the aspiration is carried out at the microsphere entry site or anywhere along the initial lymphatics. Nevertheless, puncture of the initial lymphatic endothelium with the micropipette leads to rapid aspiration of intralymphatic microspheres. Investigation of lymphatic endothelial sections fixed during lymph pumping shows open interendothelial junctions not found in resting initial lymphatics. These results suggest that initial lymphatics have a (primary) valve system at the level of the endothelium. In conjunction with the classical (secondary) intralymphatic valves, the primary valves provide the mechanism that facilitates the unidirectional flow during periodic compression and expansion of initial lymphatics.

Abdominal Muscles↗
PubMed1983

Endogenous endotoxin absorption and the role of intestinal lymphatics.

We investigated the absorption routes of endotoxin derived from the intestine of rabbits with or without thoracic duct lymph drainage (TDLD). The intestinal circulatory disorders induced were superior mesenteric artery occlusion (SMAO) and superior mesenteric vein occlusion (SMVO). Detection and quantitation of endotoxin in plasma and lymph were carried out using a synthetic chromogenic substrate (peptide-4-methyl-coumarin amide, MCA). In the SMAO group, endotoxin levels in portal plasma exceeded levels in lymph from the thoracic duct throughout the experiment, and in the SMVO group, the relationship was reversed. In peripheral arterial blood, endotoxin levels were significantly lower in rabbits with TDLD than in those with intact lymphatic system. Intestinal lymphatics probably play an important role in appearance of systemic endotoxemia in non-septic shock.

Absorption↗
PubMed2006

Live imaging of lymphatic development in the zebrafish.

The lymphatic system has become the subject of great interest in recent years because of its important role in normal and pathological processes. Progress in understanding the origins and early development of this system, however, has been hampered by difficulties in observing lymphatic cells in vivo and in performing defined genetic and experimental manipulation of the lymphatic system in currently available model organisms. Here, we show that the optically clear developing zebrafish provides a useful model for imaging and studying lymphatic development, with a lymphatic system that shares many of the morphological, molecular and functional characteristics of the lymphatic vessels found in other vertebrates. Using two-photon time-lapse imaging of transgenic zebrafish, we trace the migration and lineage of individual cells incorporating into the lymphatic endothelium. Our results show lymphatic endothelial cells of the thoracic duct arise from primitive veins through a novel and unexpected pathway.

Animals↗
PubMed1997

[Fornicate structure of blind saccular lymph vessel segments in the conjunctiva--scanning electron microscopy studies].

BACKGROUND: The accepted fundamental element of the initial lymphatic system is a tubular structure (lymphatic capillary), which is present either in the form of a finger-shaped blind-ending protuberance, or in the nature of a plexiform composite arrangement. We were able to demonstrate experimentally that the finger-shaped protuberances, which are known as "initial segments" are in fact temporary filling states. As the filling process continues, these vascular elements become intermediate segments, via which other parts of the vascular network take up the dye. To date there have been no investigations of the internal structure of these apparently blind-ending vessel segments. In this study, lymphographically represented "terminal segments" should be cut away for the purpose of examining the fornix by scanning electron microscopy. Is the internal surface of the fornix regular and unbroken, or are there fissure-like structures which could explain the observed filling processes? MATERIAL AND METHODS: In conjunctiva of bovine eyes (n = 80), interstitial double-contrast lymphography (Berlinblue solution/air) under a slit-lamp microscope was used specifically to search for finger-shaped terminal segments. The conjunctivae had previously been prepared by fixing in polymeric resins. A proportion (n = 21) of the specimens were amenable to examination under the scanning electron microscope. RESULTS: Notwithstanding the observed great variation in the shape of the lymphographically obtained blind-ending structures-in the form of terminations shaped variously like fingers, balloons, domes, pistons or pyramids, terminations with two humps, and terminations shaped like spear heads-scanning electron microscopy revealed within the fornices many relatively uniformly shaped structures in the form of fissures, configured with lips and saw-tooth edges, rather like zip fasteners. These findings are suggestive of preformed connections to neighbouring segments. This appears to be another element, in addition to the familiar flap-like structures, for controlling the circulation of lymph. Does the "initial part" of the lymphatic system now have to be redefined?

Animals↗