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[Drainage of the thoracic duct and changes in myocardial lymph drainage under conditions of electrothermocoagulation of the coronary artery].

It was demonstrated in dog experiments that the drainage function of the heart lymphatic system and coagulation of the central lymph are disturbed in acute myocardial infarction. Drainage of the thoracic duct with diversion of the flow of the toxic lymph fails to correct the diminished rate of lymph flow in the myocardium and does not prevent the increase of the hypercoagulation shift in the lymph. It is concluded that lymph stimulation and correction of the disorder of the lymph coagulation potential are necessary for effective pathogenetic treatment of myocardial infarction.

Animals↗

Cytokine profile of protective anti-Trichinella spiralis CD4+ OX22- and non-protective CD4+ OX22+ thoracic duct cells in rats: secretion of IL-4 alone does not determine protective capacity.

We analysed the cytokine profile of a T cell subset (CD4+ CD45 RC-) that confers protection against Trichinella spiralis infection in rats. These CD4+ cells are generated in the gut and appear in the thoracic duct lymph within 72 h after infection. Cytokine mRNA levels for IL-2, IL-3, IL-4, IL-5, IL-10 and IFN-gamma and functional cytokine secretion for IL-4, IL-5, IFN-gamma, TNF-alpha and mast cell differentiation activity were tested in vitro following stimulation with T. spiralis antigens. Compared to a non-protective T cell population (CD4+ CD45 RC+ or CD8+), also isolated from the same thoracic lymph, no significant differences were observed in the levels of mRNA for IL-2, IL-3, IL-4, IL-5, IL-10 or IFN-gamma in the protective CD4+ CD45 RC- cells. However, analysis of the cytokine activities in culture supernatant of these T cell subsets following 24 h stimulation in vitro with T. spiralis antigens showed that significant IL-4 and IL-5 activity but little IFN-gamma or TNF-alpha was secreted by the protective CD4+ CD45- RC- cells. Whereas the non-protective CD4+ CD45 RC+ cells secreted significant levels of IL-4, IFN-gamma, mast cell differentiating activity and TNF-alpha but little IL-5 activity. Non-protective CD8+ cells were found to secrete IL-4 but not IL-5. Production of IL-4 was essentially equal for both protective and non-protective T cell subsets. These findings suggest that the presence or absence of IFN-gamma secretion, rather than IL-4 alone, determines whether a T cell subset has protective activity against T. spiralis infection in rats.

Animals↗

Thoracic duct lymph flow and its measurement in chronically catheterized sheep fetus.

A method was developed for chronic catheterization of the left thoracic lymph duct at the base of the neck in the sheep fetus, which did not disrupt the other major lymphatic vessels that join the venous circulation at the same location. The lymphatic catheter was connected to a catheter in a jugular vein when lymph flow was not being recorded, so that the lymph continuously returned to the fetal circulation. Special consideration of catheter size to minimize flow resistance and treatment to prevent clotting were required. Individual animals were maintained up to 17 days with lymph flow continuing. In 13 fetuses averaging 128 days gestation (term = 147 days) at the time of catheterization, lymph flow rate was measured for 1 h each day for the first 7 postsurgical days with an on-line computer technique that continuously calculated lymph flow rate. Lymph flow averaged 0.64 +/- 0.17 (SD) ml/min in fetuses weighing 2.3-4 kg and tended to undergo a nonsignificant increase with time. Lymph and plasma protein concentrations did not change with time. In individual fetuses, large spontaneous variations in lymph flow rate occurred over periods of several seconds to a few minutes. Analysis showed that these variations in flow rate were not associated with fetal breathing movements. Thus the present study describes a technique for studying the dynamics of lymph flow in the unanesthetized sheep fetus in utero over a time period limited primarily by the length of gestation. In addition, it appears that thoracic duct lymph flow rate in the fetus per unit body weight averages three to four times that in the adult.

Animals↗

Estimation of the migration of thoracic duct lymphocytes to non-lymphoid tissues. A comparison of the distribution of radioactivity at intervals following i.v. transfusion of cells labelled with 3H, 14C, 75Se, 99mTc, 125I and 51Cr in the rat.

The distribution of radioisotopes in tissues was measured following i.v. injection of labelled thoracic duct lymphocytes into syngeneic rats. The rate of elution of an isotope from the labelled cells and the subsequent fate of the eluted isotope were shown to be the most important factors limiting the usefulness of such isotopes for measuring cell localization particularly in non-lymphoid tissues. Comparison of labelling procedures using [3H] and [14C]uridine, [3H] and [14C]leucine, [75Se]-L-selenomethionine, [99mTc]sodium pertechnetate and [51Cr]sodium chromate in vitro and [3H]thymidine in vivo showed that 51Cr had the fewest disadvantages in the present context. Using 51Cr-labelled cells, the radioactivity was measured in a wide range of non-lymphoid tissues, and estimates of cell traffic were obtained. In skin, for example, the results indicate a cell flux in the range of 10(4)-10(5) lymphocytes/gm/hr. Evidence is presented which suggests that the early substantial localization of labelled cells in the lung is not an artefact due to sequestration or embolization of traumatized cells but probably reflects a slow intravascular transit time through this capillary bed. The primary lymphoid organs, thymus and bone marrow were shown to include a subpopulation of lymphocytes which belong to the recirculating pool. The thymus always contained a greater concentration of radioactivity at 24 hr than all non-lymphoid tissues except liver and kidney (approx. 0-1% of the recirculating lymphocyte pool) and the bone marrow was capable of temporarily accepting a substantial proportion (approx.25%) of the injected cells.

Animals↗

Secondary delayed-type hypersensitivity to sheep red blood cells and minor histocompatibility antigens in mice: transfer of memory by recirculating thoracic duct lymphocytes.

Secondary delayed-type hypersensitivity (DTH) in mice to sheep red blood cells (SRBC) and minor histocompatibility (H) antigens is dependent on long-lived memory T cells. In this paper we investigated whether these memory T cells recirculate. It was shown that late phase "immune' thoracic duct lymphocytes (TDL) from mice which were immunized with SRBC or non-H-2-incompatible spleen cells several weeks previously could adoptively transfer secondary DTH to these antigens. Passing the immune TDL through intermediate recipients demonstrated that these SRBC- or minor H-antigen-reactive memory T cells recirculate from blood to lymph. In contrast to mice immunized with minor H antigens, no secondary type DTH reactivity could be demonstrated in mice immunized with H-2-incompatible spleen cells. Also, after adoptive transfer of TDL from mice immunized with H-2-alloantigens, it was impossible to demonstrate an accelerated DTH reactivity.

Animals↗

Allograft rejection in athymic nude rats by transferred T-cell subsets. I. The response of naive CD4+ and CD8+ thoracic duct lymphocytes to complete allogeneic incompatibilities.

PVG.rnu/rnu nude rats were pre-grafted with two allogeneic skin grafts, AO(RTlu) and BN(RTln), 6-14 days in advance of cell transfer. Cellular requirements for rejection were established by transferring graded numbers of B cell-depleted (Ig-) thoracic duct lymphocytes (TDL) or purified W3/25+ (CD4+) or OX8+ (CD8+) TDL subsets. Allografts were rejected by 10(5) to 5 x 10(6) Ig- TDL in a dose-dependent fashion. A similar dose-response relationship was found by transferring 5 x 10(5) to 5 x 10(6) Ig- OX8- TDL (purified by depletion of B cells and OX8+ cells). Larger numbers of Ig- OX8- TDL (10-30 x 10(6)) did not significantly accelerate rejection. W3/25+ TDL alone (10(5)), highly purified by fluorescence-activated cell sorting (FACS), were sufficient to induce allograft rejection in this athymic nude rat model. In contrast, 10 times more FACS purified OX8+ TDL (10(6)) were unable to initiate skin graft rejection despite the complete class I and class II MHC incompatibilities. Furthermore, the addition of 10(6) OX8+ cells did not accelerate or retard the rejection induced by 10(5) W3/25+ cells alone. Pre-grafted nude recipients, irradiated (500 R) 2 hr before W3/25+ TDL injection, in order to eliminate putative nude T cells, rejected allografts on the same day as unirradiated controls. We conclude that when confronted with complete MHC disparities, CD4+ T cells are necessary and sufficient to induce skin allograft rejection whereas CD8+ T cells do not appear to contribute.

Animals↗

A search for an enriched source of polymeric IgA in human thoracic duct lymph, portal vein blood and aortic blood.

Because human bile contains a lot of secretory IgA, it has been suspected that the human liver, like rat liver, transfers polymeric IgA from plasma to bile. Hence, a rich source of polymeric IgA might enter the general circulation of man. We examined human thoracic duct lymph, portal vein blood and aortic blood for content and molecular size of IgA. None of the fluids was found to have either a higher total concentration of IgA or a higher proportion of polymeric IgA than that found in peripheral venous blood. It is possible that hepatic clearance of plasma IgA does not occur in man to the extent that it does in the rat, and a relatively larger proportion of human biliary IgA might originate from synthesis in hepatobiliary tissues.

Aged↗

The effect of intravenous administration of fat emulsion on the flow rate and composition of thoracic duct lymph in the dog.

In seven dogs weighing 17-25 kg, the terminal segment of the thoracic duct was isolated, under total pentobarbital anesthesia, so as to collect lymph continuously before, during and after infusion of a 20% fat emulsion Intralipid (Vitrum). Arterial blood and lymph were withdrawn simultaneously for analysis of total protein, amylase, cholesterol, triglycerides, urea and AST. The lymph flow rate was calculated in ml/min. Compared with the control period, during which a 5% glucose solution was administered, a two-hour infusion of the fat emulsion did not change the lymph flow rate nor the levels of biochemical parameters monitored in lymph. These results distinguish intravenous administration of a fat emulsion from a situation, in which fat is administered orally. The unchanged lymph amylase levels following fat administration suggest that no significant stimulation of external pancreatic secretion occurs after this route of fat administration.

Journal Article↗

[Ultrastructure of immunocytes in the lymph of the thoracic duct during rejection of the allogenically transplanted heart in the dog].

Substructural changes in the immunocytes of thoracic duct lymphatic fluid were studied in allogeneous heart transplant experiments on 47 dogs in an effort to identify factors associated with or inductive of the process of rejection. The initial changes could be shown to be related to the inevitable trauma associated with the transplant procedure. At the same time evidence of increased physiologic activity of the cells begins to appear and lymphoplasmocytes begin to enter the process along with the onset of antibody production. Immediately before rejection occurs, the number of lymphoplasmocytes increases which however often show degenerative changes on ultrastructural examination.

Animals↗

The secretion of catecholamines, chromogranin A and neuropeptide Y from the adrenal medulla of the cat via the adrenolumbar vein and thoracic duct: different anatomic routes based on size.

Secretion of the adrenal medulla was stimulated in nine cats by insulin-induced hypoglycemia. Levels of catecholamines (mol. wt 153-183), neuropeptide Y (mol. wt 4254) and chromogranin A (mol. wt 48,000) were measured in concurrently collected samples of adrenolumbar venous blood and thoracic duct lymph for up to 4 h following insulin administration. Insulin-induced hypoglycemia elicited an increase in the secretion of catecholamines, which reached peak levels in the adrenolumbar venous plasma at 1.5-2 h and in the lymph at 2.5 h. Although catecholamines were the most numerous measured molecules in the lymph, levels of norepinephrine and epinephrine were 75-250-fold less than those found in the adrenolumbar venous plasma. Neuropeptide Y in the adrenolumbar venous plasma reached peak levels between 1 and 1.5 h; at this time approximately 20% of the peak venous amount was detected in the lymph. Chromogranin A was found in approximately equal amounts in both plasma and lymph; the peak level in the plasma occurred at 1.5-2 h, while that in the lymph was reached at 2-3 h. We suggest that the size of a molecule influences the route it takes following exocytosis from the chromaffin vesicle. Smaller molecules such as catecholamines may pass directly into the circulation, while larger molecules such as chromogranin A may be temporarily sequestered in the interstitial space before passing into the lymph, and hence into the circulation.

Adrenal Medulla↗

Lymphatic thoracic duct ligation modulates the serum levels of IL-1beta and IL-10 after intestinal ischemia/reperfusion in rats with the involvement of tumor necrosis factor alpha and nitric oxide.

Intestinal ischemia/reperfusion (I/R) causes local and remote injuries that are multifactorial and essentially inflammatory in nature. To study the putative influences of nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) on the release of interleukin (IL) 1beta and IL-10 and the involvement of lymphatic system on a systemic inflammation caused by I/R, we have quantified the serum and lymph levels of IL-1beta and IL-10 in rats during I/R after treatment with inhibitors of NO synthase (N-nitro-L-arginine methyl ester hydrochloride [L-NAME]) or TNF-alpha (pentoxifylline [PTX]). Intestinal I/R was performed by means of a 45-min occlusion of the mesenteric artery, followed by 2-h reperfusion; groups of rats subjected to I/R had the thoracic lymph duct ligated immediately before the procedure. The I/R caused a significant increase of the serum levels of IL-1beta and IL-10 in rats with intact thoracic lymph duct, whereas the thoracic duct ligation blunted the serum release of IL-1beta and elevated that of IL-10. The levels of the cytokines collected in the lymph after I/R increased, and even more increase was observed in L-NAME-treated rats. L-NAME significantly increased the lymph levels of IL-1beta and IL-10; in serum, however, only IL-1beta increased in rats with either intact or ligated thoracic lymph duct. The treatment with PTX reduced the serum levels of IL-1beta irrespective of the lymph circulation interruption but was effective to increase the IL-10 levels in intact rats during I/R. The lymphatic levels of IL-1beta of rats subjected to I/R were reduced and those of IL-10 were increased after treatment with PTX. In conclusion, during I/R, the serum levels of IL-1beta seem modulated by stimulant mechanisms that could be associated with TNF-alpha and inhibited by NO and by the integrity of the thoracic lymphatic flow. On the other hand, IL-10 seems controlled by TNF-alpha-related, largely NO-independent mechanisms. Thus, it is reasonable to suppose that an endogenous mechanism that can limit the systemic inflammatory response ensuing an I/R splanchnic trauma exists.

Animals↗