Lymphatic Pumping Research Articles

Lymphatic pump treatment reduces pulmonary tumors in the rat

Lymphatic pump treatment reduces pulmonary tumors in the rat

A novel method of measuring human lymphatic pumping using indocyanine green fluorescence lymphography

Lymph transportation through the body is partly controlled by the intrinsic pumping of lymphatic vessels. Although an understanding of this process is important for medical application, little is currently known because it is difficult to measure. Here, we introduce an easy, safe, and cost-effective technique for measuring lymphatic pumping in leg superficial lymphatic vessels. Readings obtained with this technique were compared with values obtained with dynamic lymphoscintigraphy. Differences in lymphatic pumping between healthy volunteers and patients with lymphedema were also investigated. Indocyanine green (ICG) fluorescence lymphography was performed by subcutaneously injecting 0.3 mL of ICG (0.5%) into the dorsum of the foot. Real-time fluorescence images of lymph propulsion were obtained with an infrared-light camera system with the individual supine or sitting. A custom-made transparent sphygmomanometer cuff was wrapped around the lower leg and connected to a standard mercury sphygmomanometer. The cuff was inflated to 60 mm Hg and then gradually deflated at 5-minute intervals to lower the pressure by 10-mm Hg steps until the fluorescence contrast agent exceeded the upper border of the cuff, indicating that the lymphatic contraction had overcome the cuff pressure. Lymph pumping pressure (P(pump)) was defined as the value of the cuff pressure when the contrast agent exceeded the upper border of the cuff. We measured P(pump) among healthy volunteers who maintained a supine position and compared these values with measurements obtained from lymphoscintigraphy. P(pump) values while sitting were also compared between 30 legs from healthy volunteers and 30 legs from lymphedematous patients. Among healthy, supine participants, P(pump) was 25.2 ± 16.7 mm Hg (mean ± standard deviation [SD]) when measured by ICG fluorescence lymphography. These values were significantly correlated with values taken using dynamic lymphoscintigraphy (r(2) = 0.54, p < .01), while 2 SDs of the mean were approximately 20 mm Hg, suggesting a substantial disagreement between the two methods (Bland-Altman plots). In the comparison of seated measurements, readings for healthy participants (P(pump) = 29.3 ± 16.0) were higher than those for lymphedematous participants (13.2 ± 14.9). ICG fluorescence is an accurate-as well as a safe, easy, and economical-method of measuring lymphatic pumping. Therefore, it may develop as a vital tool for diagnosing lymphatic malfunctions even when they are only in their formative stages. Studies that use this technique may increase our knowledge of the lymphatic system as a whole, allowing us to develop better treatments for lymphatic disorders.

Adaptation of Mesenteric Collecting Lymphatic Pump Function Following Acute Alcohol Intoxication

Acute alcohol intoxication increases intestinal lymph flow by unknown mechanisms, potentially impacting mucosal immunity. We tested the hypothesis that enhanced intrinsic pump function of mesenteric lymphatics contributes to increased intestinal lymph flow during alcohol intoxication. Acute alcohol intoxication was produced by intragastric administration of 30% alcohol to conscious, unrestrained rats through surgically implanted catheters. Time-matched controls received either no bolus, vehicle, or isocaloric dextrose. Thirty minutes after alcohol administration, rats were anesthetized and mesenteric collecting lymphatics were isolated and cannulated to study intrinsic pumping parameters. In separate experiments, mesenteric lymphatics were isolated to examine direct effects of alcohol on intrinsic pump activity. Lymphatics isolated from alcohol-intoxicated animals displayed significantly decreased CF compared to the dextrose group, elevated SVI versus all other groups, and decreased myogenic responsiveness compared to sham. Elevating pressure from 2 to 4 cm H₂O increased the volume flow index 2.4-fold in the alcohol group versus 1.4-fold for shams. Isolated lymphatics exposed to 20 mM alcohol had reduced myogenic tone, without changes in CF or SVI. Alcohol intoxication enhances intrinsic pumping by mesenteric collecting lymphatics. Alcohol directly decreases lymphatic myogenic tone, but effects on phasic contractions occur by an unidentified mechanism.

Lymphatic Pump Treatment Mobilizes Leukocytes from the Gut Associated Lymphoid Tissue into Lymph

Lymphatic pump techniques (LPT) are used clinically by osteopathic practitioners for the treatment of edema and infection; however, the mechanisms by which LPT enhances lymphatic circulation and provides protection during infection are not understood. Rhythmic compressions on the abdomen during LPT compress the abdominal area, including the gut-associated lymphoid tissues (GALT), which may facilitate the release of leukocytes from these tissues into the lymphatic circulation. This study is the first to document LPT-induced mobilization of leukocytes from the GALT into the lymphatic circulation. Catheters were inserted into either the thoracic or mesenteric lymph ducts of dogs. To determine if LPT enhanced the release of leukocytes from the mesenteric lymph nodes (MLN) into lymph, the MLN were fluorescently labeled in situ. Lymph was collected during 4 min pre-LPT, 4 min LPT, and 10 min following cessation of LPT. LPT significantly increased lymph flow and leukocytes in both mesenteric and thoracic duct lymph. LPT had no preferential effect on any specific leukocyte population, since neutrophil, monocyte, CD4+ T cell, CD8+ T cell, IgG+B cell, and IgA+B cell numbers were similarly increased. In addition, LPT significantly increased the mobilization of leukocytes from the MLN into lymph. Lymph flow and leukocyte counts fell following LPT treatment, indicating that the effects of LPT are transient. LPT mobilizes leukocytes from GALT, and these leukocytes are transported by the lymphatic circulation. This enhanced release of leukocytes from GALT may provide scientific rationale for the clinical use of LPT to improve immune function.

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

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 T(7)-T(9) 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 +/- 0.75 N/m was observed with a corresponding passive tension of 3.11 +/- 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 +/- 4.7 and 20.6 +/- 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-A(2) analog U-46619 evoked phasic contractions (analogous to lymphatic pumping), whereas at higher contractions they induced tonic activity (maximum tension values of 4.46 +/- 0.63, 5.90 +/- 1.4, and 6.78 +/- 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 approximately 20% and approximately 40%, 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 Pump Manipulation Mobilizes Inflammatory Mediators into Lymphatic Circulation

Lymph stasis can result in edema and accumulation of particulate matter, exudates, toxins, and bacteria. This can lead to inflammation, impaired immune cell trafficking, tissue hypoxia, tissue fibrosis, and a variety of diseases. Previously, we demonstrated that osteopathic lymphatic pump treatment (LPT) significantly increased thoracic and mesenteric duct lymph flow. The purpose of this study was to determine if LPT would mobilize inflammatory mediators into the lymphatic circulation. Under anesthesia, thoracic or mesenteric lymph of dogs was collected at baseline (resting), during 4 min of LPT, and 10 min following LPT and the lymphatic concentrations of cytokines, chemokines, superoxide dismutase (SOD) and nitric oxide (NO) were measured. LPT significantly increased both thoracic and mesenteric lymph cytokine and chemokine concentrations when compared to their relative baseline concentrations. In addition, LPT increased lymphatic concentrations of SOD and NO. Ten minutes following cessation of LPT, both thoracic and mesenteric lymph cytokine, chemokine, NO and SOD concentrations were similar to baseline, suggesting their release is transient. This redistribution of inflammatory mediators during LPT may provide scientific rationale for the clinical use of LPT to enhance immunity and treat infection. Funding: NIH: U19 AT002023 (H. F.D), R01 AT004361 (L.M.H).

Lymphatic Pump Treatment Increases Thoracic Duct Lymph Flow in Conscious Dogs with Edema Due to Constriction of the Inferior Vena Cava

ObjectiveTo examine the effects of osteopathic lymphatic pump treatment (LPT) on lymph flow in the thoracic duct of instrumented conscious dogs in the presence of edema produced by constriction of the inferior vena cava (IVC).MethodsSix dogs were surgically instrumented with an ultrasonic flow transducer on the thoracic lymph duct and catheters in the descending thoracic aorta and in the IVC. After post‐operative recovery, lymph flow and hemodynamic variables were measured 1) pre‐LPT, 2) during 4 min LPT, 3) post‐LPT, in the absence and presence of edema produced by IVC constriction.ResultsIVC constriction increased abdominal girth from 60±2.6 to 75±2.9 cm. Before IVC constriction, LPT increased lymph flow (P&lt;0.05) from 1.9±0.2 ml/min to a maximum of 4.7±1.2 ml/min, whereas after IVC constriction, LPT increased lymph flow (P&lt;0.05) from 7.9±2.2 to a maximum of 11.7±2.2 ml/min. The incremental lymph flow mobilized by 4 min of LPT, i.e., the flow that exceeded 4 min of baseline flow, was 10.6 ml after IVC constriction (not different from before IVC constriction).ConclusionsEdema caused by IVC constriction markedly increased lymph flow in the thoracic duct. LPT increased thoracic duct lymph flow before and after IVC constriction. The lymph flow mobilized by 4 min of LPT in presence of edema was not significantly greater than that mobilized prior to edema. (Support: NIH grant U19 AT002023 and Osteopathic Research Center.)

Aging of the Mesenteric Lymph Pump

All functions of lymphatic system require the effective lymph flow, which cannot exist without effective contractions of muscle cells of lymphatic vessels (LV). However, the mechanisms regulating the lymphatic pumping, including its age‐related alterations, remain greatly under investigated. In this study we tested the hypothesis that contractility of mesenteric LV (MLV) is affected by aging including disturbed NO/flow‐dependent modulation. Parameters of lymphatic pumping of isolated, cannulated &amp; pressurized segments of MLV were measured in F‐344 9‐ and 24‐mo old rats. The influences of incrementally increased transmural pressure and imposed flow were examined before &amp; after treatment with L‐NAME 10‐4 M. We observed that negative inotropic and chronotropic effects of aging in MLV result in a 2–2.5‐fold decrease in their pump productivity. The flow/NO‐dependent regulation of lymphatic pumping is greatly disturbed in aged MLV. At the same time, we observed the evidence of flow‐independent NO release in aged MLV. Data suggest the existence of age‐induced alterations in NO synthase‐dependent modulation of MLV pump activity. We conclude that depletion of contractile reserves in aged MLV diminishes their ability to provide the adequate transport of lymph in mesenteric lymphatic network especially during periods of the increased lymph formation, which would occur after meal consumption. NIH RO1 AG030578.

Impact of Lymphatic Vessels on the Heart

This review updates the knowledge in the research field of cardiac lymphatic vessels by collecting both scientific evidence and hypotheses, including cardiac lymphatic vessel anatomy and lymph flow, the mechanism of cardiac lymphatic pumping, pathological findings and mechanisms of cardiac injury caused by lymph flow impairment, cardiac functional improvement by increasing lymph flow in the heart in patients with myocardial infarction, and the mechanisms of lymphangiogenesis.

Characterization of biosynthesis and modes of action of prostaglandin E2 and prostacyclin in guinea pig mesenteric lymphatic vessels

Rhythmical transient constrictions of the lymphatic vessels provide the means for efficient lymph drainage and interstitial tissue fluid balance. This activity is critical during inflammation, to avoid or limit oedema resulting from increased vascular permeability, mediated by the release of various inflammatory mediators. In this study, we investigated the mechanisms by which prostaglandin E(2) (PGE(2)) and prostacyclin modulate lymphatic contractility in isolated guinea pig mesenteric lymphatic vessels. Quantitative RT-PCR was used to assess the expression of mRNA for enzymes and receptors involved in the production and action of PGE(2) and prostacyclin in mesenteric collecting lymphatic vessels. Frequency and amplitude of lymphatic vessel constriction were measured in the presence of these prostaglandins and the role of their respective EP and IP receptors assessed. Prostaglandin E(2) and prostacyclin decreased concentration-dependently the frequency, without affecting the amplitude, of lymphatic constriction. Data obtained in the presence of the EP(4) receptor antagonists, GW627368x (1 microM) and AH23848B (30 microM) and the IP receptor antagonist CAY10441 (0.1 microM) suggest that PGE(2) predominantly activates EP(4), whereas prostacyclin mainly stimulates IP receptors. Inhibition of responses to either prostaglandin with H89 (10 microM) or glibenclamide (1 microM) suggested a role for the activation of protein kinase A and ATP-sensitive K(+) channels. Our findings characterized the inhibition of lymphatic pumping induced by PGE(2) or prostacyclin in guinea pig mesenteric lymphatics. This action is likely to impair oedema resolution and to contribute to the pro-inflammatory actions of these prostaglandins.

Systematic Review of Efficacy for Manual Lymphatic Drainage Techniques in Sports Medicine and Rehabilitation: An Evidence-Based Practice Approach

Manual therapists question integrating manual lymphatic drainage techniques (MLDTs) into conventional treatments for athletic injuries due to the scarcity of literature concerning musculoskeletal applications and established orthopaedic clinical practice guidelines. e purpose of this systematic review is to provide manual therapy clinicians with pertinent information regarding progression of MLDTs as well as to critique the evidence for e cacy of this method in sports medicine. We surveyed English-language publications from 1998 to 2008 by searching PubMed, PEDro, CINAHL, the Cochrane Library, and SPORTDiscus databases using the terms lymphatic system, lymph drainage, lymphatic therapy, manual lymph drainage, and lymphatic pump techniques. We selected articles investigating the effects of MLDTs on orthopaedic and athletic injury outcomes. Nine arti- cles met inclusion criteria, of which 3 were randomized controlled trials (RCTs). We evaluated the 3 RCTs using a validity score (PEDro scale). Due to di erences in experimental design, data could not be collapsed for meta-analysis. Animal model experiments reinforce theoretical principles for application of MLDTs. When combined with concomitant musculoskeletal therapy, pilot and case studies demonstrate MLDT e ectiveness. e best evidence suggests that the efficacy of MLDT in sports medicine and rehabilitation is specific to resolution of enzyme serum levels associated with acute skeletal muscle cell damage as well as reduction of edema following acute ankle joint sprain and radial wrist fracture. Currently, there is limited high-ranking evidence available. Well-designed RCTs assessing outcome variables following implementation of MLDTs in treating athletic injuries may provide conclusive evidence for establishing applicable clinical practice guidelines in sports medicine and rehabilitation.

Contractile physiology of lymphatics.

The lymphatic system has important roles in body fluid regulation, macromolecular homeostasis, lipid absorption, and immune function. To accomplish these roles, lymphatics must move fluid and its other contents (macromolecules, lipids/chylomicra, immune cells) from the interstitium through the lymphatics, across the nodes, and into the great veins. Thus, the principal task of the lymphatic vascular system is transport. The body must impart energy to the lymph via pumping mechanisms to propel it along the lymphatic network and use pumps and valves to generate lymph flow and prevent its backflow. The lymphatic system utilizes both extrinsic pumps, which rely on the cyclical compression and expansion of lymphatics by surrounding tissue forces, and intrinsic pumps, which rely on the intrinsic rapid/phasic contractions of lymphatic muscle. The intrinsic lymph pump function can be modulated by neural, humoral, and physical factors. Generally, increased lymph pressure/stretch of the muscular lymphatics activates the intrinsic lymph pump, while increased lymph flow/shear in the muscular lymphatics can either activate or inhibit the intrinsic lymph pump depending on the pattern and magnitude of the flow. To regulate lymph transport, lymphatic pumping and resistance must be controlled. A better understanding of these mechanisms could provide the basis for the development of better diagnostic and treatment modalities for lymphatic dysfunction.

Low density lipoprotein modulates rat mesenteric lymphatic pumping

The unique nature &amp; location of mesenteric lymphatics provides a special site for modulating lipoprotein transport, including low density lipoprotein (LDL). Intestinal lymph contains both enterocyte‐synthesized &amp; plasma‐derived lipoproteins. Lipid absorption is associated with alterations in mesenteric lymph pressure &amp; flow, implying that they coordinate lymph transport with intestinal lipid absorption by adjusting lymph pump flow. However, detailed studies of the mechanisms involved haven't been done, so we studied this process in isolated rat mesenteric lymphatics. We found: 1. Prominent expression of LDL receptors in lymphatic cells, endocytosis of LDL into lymphatic endothelium, and endothelial NO synthase (eNOS) expression in lymphatic endothelium; 2. LDL up‐regulates phasic contraction frequency and alters tone, resulting in a significant increase in the lymph pump output. Therefore we hypothesize that: LDL exposure, acting through its receptors and/or modulations of eNOS activity, provides positive feedback to the lymphatic pump via increases in the phasic contraction frequency with accompanying alterations of the tone. These studies may help correlate lymphatic function with lipoprotein metabolism and provide the basis for the prevention and treatment of the disorders related to lipoprotein metabolism. NIH HL70308 &amp; HL80526

CGMP/PKG‐mediated regulation of lymphatic contractility

Recently we demonstrated a principal role of nitric oxide (NO) in the endothelium/shear‐dependent regulation of contractility in thoracic duct (TD). We tested the hypothesis that cGMP/PKG is involved in the intrinsic &amp; extrinsic flow‐dependent modulation of lymphatic contractility. Diameters &amp; indices of lymphatic pumping of isolated, cannulated &amp; pressurized segments of rat TD were measured. The influences of incrementally increased transmural pressure (1 to 5 cm H2O) and imposed flow (1 to 5 cm H2O transaxial pressure gradient) were examined before &amp; after treatment with cGMP analog and antagonist. We found that the cGMP analog ‐ 8pCPTcGMP (1‐100 µM) mimics the extrinsic flow‐induced relaxation in a dose‐dependent manner. Treatment of TD by the cGMP/PKG inhibitor ‐ Rp‐8‐Br‐PET‐cGMPS (10‐50 µM) eliminated the NO‐dependent intrinsic flow‐dependent relaxation, and largely prevented the extrinsic flow‐dependent relaxation. Western blotting demonstrated the presence of both PKGα and β isoforms in TD, with ~10‐times greater expression of the PKGα protein in TD compared with aorta and vena cava. The PKGβ isoform expressed equally in TD and vena cava, both being ~2 times higher than that in the aorta. These findings demonstrate that cGMP is critical to the flow‐dependent regulation of TD contractility; and also suggests important involvement of PKG in these processes. NIH HL70308

AGING AND LYMPHATIC CONTRACTILITY

All functions of lymphatic system require the lymph flow, which can not exist without the driving force generated by contractions of lymphatic vessels (LV). However the mechanisms regulating the lymphatic contractility and particularly the mechanisms of age‐related alterations in lymphatic pumping remain greatly under discovered. Using confocal imaging we observed the profound reduction of muscle cells in aged rat LV. In vivo flow measurements using fast video microscopy demonstrated greatly decreased basal lymph flow; maximal lymphocyte velocities in aged mesenteric LV are 4‐6 times lower than in the adult LV, contraction amplitude diminished by 50‐60%; while the contractions are irregular with long periods of inactivity. The profound inhibition of the contractile activity has been observed also in isolated aged rat thoracic duct (TD) and mesenteric LV. The basic flow/eNOS‐dependent regulation is abolished in aged TD, protein message is greatly depleted. At the same time in aged TD the substantial iNOS activation, confirmed by Western blotting and immunohistochemistry, occurs; its functional importance confirmed by pressure/flow tests. We concluded that depletion of the contractile reserves in LV in elderly diminishes their ability to provide the adequate transport of lymph during the periods of the increased volumetric loads. Support: NIH RO1 AG030578, HL070308, HL080526, TAMU CERH 5 P30 ES09106‐08.

Venomotion modulates lymphatic pumping in the bat wing

In skin, it is believed that lymph must be pumped by intrinsic contraction of lymphatic muscle, since investigators have not considered that cyclical dilation of venules could compress adjacent lymphatic microvessels. Because lymphatic vessels are sensitive to stretch, we hypothesized that venomotion not only can cause extrinsic pumping of lymph in nearby lymphatic vessels, but also can stimulate intrinsic contractions. Bat wing venules have pronounced venomotion and are in close proximity to lymphatic microvessels, and can be studied noninvasively without the confounding effects of anesthesia, surgical trauma, or contrast agents. Therefore, the interaction between venules and their paired lymphatic vessels in unanesthetized Pallid bats (n = 8) was evaluated by recording the diameters of both vessels. Four sets of observations suggested that lymphatic and venous contractions were partially coupled. First, venous dilation and contraction produced a significant change in lymphatic microvascular cross-sectional area. Second, lymphatic microvascular contractions were immediately preceded by a change in venular diameter. Third, venular and lymphatic vessel contraction frequencies were positively correlated (r = 0.75). Fourth, time delays between peak venular systole and onset of lymphatic microvascular contraction were negatively correlated with venomotion magnitude (r = -0.55) and velocity (r = -0.64). In a separate experiment, inhibiting venomotion resulted in a 54.3 +/- 20.0% (n = 8) decrease in lymphatic contraction frequency. Furthermore, 85.7% (n = 56) of lymphatic vessels switch sides and lie adjacent to arterioles when venules were too small to exhibit venomotion. These results are consistent with both extrinsic pumping of lymph and stretch-induced lymphatic contraction and imply that intrinsic and extrinsic pumping can be coupled.

Recent Advances in Breast Cancer-Related Lymphedema of the Arm: Lymphatic Pump Failure and Predisposing Factors

Axillary surgery for breast cancer may be followed, months to years later, by chronic arm lymphedema. A simple 'stopcock' mechanism (reduced lymph drainage from the entire limb through surviving lymphatics) does not explain many clinical aspects, including the delayed onset and selective sparing of some regions, e.g., hand. Quantitative lymphoscintigraphy reveals that lymph drainage is slowed in the subcutis, where most of the edema lies, and in the subfascial muscle compartment, which normally has much higher lymph flows than the subcutis. Although the muscle does not swell significantly, the impaired muscle drainage correlates with the severity of arm swelling, indicating a likely key role for muscle lymphatic function. A new method, lymphatic congestion lymphoscintigraphy, showed that the edema is associated with a reduced contractility of the arm lymphatics; the weaker the active lymphatic pump, the greater the swelling. Delayed lymphatic pump failure may result from chronic raised afterload, as in hypertensive cardiac failure, and may account for the delayed onset of swelling. A further novel finding is that lymph flow is raised in both the subcutis and muscle of both arms in postsurgical breast patients who later developed breast cancer-related lymphedema (BCRL), compared with patients who did not develop BCRL. This new observation indicates a predisposition to BCRL in some women. Further evidence for predisposing abnormalities is the finding of lymphatic abnormalities in the contralateral (nonswollen) arm in women with established BCRL. Such predisposing factors could explain why some women develop BCRL after sentinel node biopsy, whereas others do not after clearance surgery. Future research must focus on prospective observations made from before surgery until BCRL develops.

Rate‐sensitive contractile responses of lymphatic vessels to circumferential stretch

Phasic contractile activity in rat portal vein is more sensitive to the rate of change in length than to absolute length and this response is widely assumed to be a general characteristic of myogenic behaviour for vascular smooth muscle. Previously, we found that rat lymphatic vessels exhibit phasic contractile behaviour similar to that of portal vein. In the present study, we hypothesized that lymphatic muscle would exhibit rate-sensitive contractile responses to stretch. The hypothesis was tested on rat mesenteric lymphatics (90-220 microm, i.d.) using servo-controlled wire- and pressure-myograph systems to enable ramp increases in force or pressure at different rates. Under isometric conditions in wire-myograph preparations, both the amplitude and the frequency of phasic activity were enhanced at more optimal preloads, but superimposed upon this effect were bursts of contractions that occurred only during fast preload ramps. In such cases, the ratio of contraction frequency during the ramp to that at the subsequent plateau (at optimal preload) was > 1. Further, the frequency ratio increased as a function of the preload ramp speed, consistent with a rate-sensitive mechanism. In contrast, the amplitude ratio was < 1 and declined further with higher ramp speeds. Downward preload ramps produced corresponding rate-sensitive inhibition of contraction frequency but not amplitude. Similar findings were obtained in pressurized lymphatics in response to pressure ramps and steps. Our results suggest that lymphatics are sensitive to the rate of change in preload/pressure in a way that is different from portal vein, possibly because the pacemaker for generating electrical activity is rate sensitive but lymphatic muscle is not. The behaviour may be widely present in collecting lymphatic vessels and is probably an important mechanism for rapid adaptation of the lymphatic pump to local vascular occlusion.

The immediate effect of individual manipulation techniques on pulmonary function measures in persons with chronic obstructive pulmonary disease.

BackgroundThe use of manipulation has long been advocated in the treatment of chronic obstructive pulmonary disease (COPD), but few randomized controlled clinical trials have measured the effect of manipulation on pulmonary function. In addition, the effects of individual manipulative techniques on the pulmonary system are poorly understood. Therefore, the purpose of this study was to determine the immediate effects of four osteopathic techniques on pulmonary function measures in persons with COPD relative to a minimal-touch control protocol.MethodsPersons with COPD aged 50 and over were recruited for the study. Subjects received five, single-technique treatment sessions: minimal-touch control, thoracic lymphatic pump (TLP) with activation, TLP without activation, rib raising, and myofascial release. There was a 4-week washout period between sessions. Protocols were given in random order until all five techniques had been administered. Pulmonary function measures were obtained at baseline and 30-minutes posttreatment. For the actual pulmonary function measures and percent predicted values, Wilcoxon signed rank tests were used to test within-technique changes from baseline. For the percent change from baseline, Friedman tests were used to test for between-technique differences.ResultsTwenty-five subjects were enrolled in the study. All four tested osteopathic techniques were associated with adverse posttreatment changes in pulmonary function measures; however, different techniques changed different measures. TLP with activation increased posttreatment residual volume compared to baseline, while TLP without activation did not. Side effects were mild, mostly posttreatment chest wall soreness. Surprisingly, the majority of subjects believed they could breathe better after receiving osteopathic manipulation.ConclusionIn persons with COPD, TLP with activation, TLP without activation, rib raising, and myofascial release mildly worsened pulmonary function measures immediately posttreatment relative to baseline measurements. The activation component of the TLP technique appears to increase posttreatment residual volume. Despite adverse changes in pulmonary function measures, persons with COPD subjectively reported they benefited from osteopathic manipulation.

Lymphatic pump treatment mobilizes leukocytes from the gut associated lymphoid tissue into thoracic duct lymph

s from the 7 International Conference on Advances in Osteopathic Research (ICAOR 7), Bradenton, Florida, USA 5e7 September 2008 Lymphatic pump treatment mobilizes leukocytes from the gut associated lymphoid tissue into thoracic duct lymph Artur Schander , Melissa K. Bearden , Jamie B. Huff , Arthur Williams Jr., Scott T. Stoll , Jerry W. Simecka , Hollis H. King , H. Fred Downey , Lisa M. Hodge a,b a Department of Molecular Biology and Immunology, University of North Texas Health Science Center at Fort Worth, TX b National Osteopathic Research Center, University of North Texas Health Science Center at Fort Worth, TX c Department of Integrative Physiology, University of North Texas Health Science Center at Fort Worth, TX Rhythmic compressions on the abdomen during lymphatic pump treatment (LPT) most likely compress the abdominal area, including the spleen and gastrointestinal mucosa, which may facilitate the release of leukocytes from these tissues into circulation. To determine the acute effects of LPT on canine intestinal lymph leukocytes, a catheter was inserted into the large intestinal lymph duct. In a separate set of experiments, the thoracic lymph duct was cannulated and 25-50% of the mesenteric lymph nodes (MLN) were fluorescently labeled in situwith carboxyfluorescein diacetate succinimidyl ester (CFSE). The abdominal incision was closed, and thoracic duct lymph was collected at baseline, during 4 min of LPT, and during 10 min following LPT. Total leukocytes in both thoracic duct and intestinal duct lymph were enumerated, and the number of neutrophils, macrophages, and lymphocytes was determined by differential cell staining. In addition, the percentage of CFSE labeled leukocytes (reflective of cells from the MLN), B cells, CD4+ T cells, CD8+ T cells, IgA and IgG antibody forming cells were measured by flow cytometry. Within the first 2 min of LPT, leukocytes are mobilized into intestinal and thoracic duct lymph circulation; however, larger increases in thoracic duct leukocytes appear later, in the last 2-4 min of treatment, and stay elevated during recovery while intestinal leukocyte numbers decrease. Flow cytometry and differential cell staining revealed that CD4+ T cells, CD8+ T cells, B cells and IgG antibody forming cells numbers were similarly increased during LPT. Interestingly, the baseline population of IgA forming cells was 6.10 1.80%, which increased to 8.75 2.62 % during LPT, suggesting that LPT acts preferentially on mucosal-derived cells. Furthermore, LPT increased the percentage of CFSE labeled leukocytes in the thoracic duct lymph from 15% to 22.6%, suggesting that the MLN are a tissue source that LPT can release leukocytes from. Collectively, these data suggest that LPT immediately releases leukocytes from the intestine that enter lymph circulation and reach the thoracic duct within 2-4 min. Furthermore, increased numbers of CFSE labeled leukocytes in thoracic duct lymph during LPT suggests that LPT can mobilize T and B cells from theMLN into the thoracic duct lymph. The gut associated lymphoid tissue (GALT) is an inductive tissue of antigen-specific leukocytes which migrate fromGALT into other mucosal associated tissues, such as the lung. Therefore, treatments, such as LPT, that specifically mobilize leukocytes from GALT may increase the numbers of leukocytes that are able to traffic into the lung during pulmonary infection. Funding for this project was provided by the National Institutes of Health (Grant No. U19 AT002023-01A1) and UNTHSC (Grant No. G67717). doi:10.1016/j.ijosm.2008.08.002