Lymph Flow Rate Research Articles

In vivo diffusion of immunoglobulin G in muscle: effects of binding, solute exclusion, and lymphatic removal.

Previously, we demonstrated that immunoglobulin G (IgG), dissolved in an isotonic solution in the peritoneal cavity, transported rapidly into the abdominal wall when the intraperitoneal (ip) pressure was > 2 cmH2O. We hypothesized that this was chiefly caused by convection and that diffusion of IgG was negligible. To investigate the role of diffusion, we dialyzed rats with no pressure gradient across the abdominal wall muscle for 2 or 6 h with an ip isotonic solution containing 125I-labeled IgG. At the end of the experiment, the animal was euthanized and frozen and abdominal wall tissue was processed to produce cross-sectional autoradiograms. Quantitative densitometric analysis resulted in IgG concentration profiles with far lower magnitude than profiles from experiments in which convection dominated. In other in vivo experiments, we determined the lymph flow rate to be 0.8 x 10(-4) ml.min-1.g-1 and the fraction of extravascular tissue (theta s) available to the IgG to be 0.041 +/- 0.001. An in vitro binding assay was used to determine the time-dependent, nonsaturable binding constant: 0.0065 min-1 x duration of exposure. A non-steady-state diffusion model that included effects of theta s, time-dependent binding, and lymph flow was fitted to the diffusion profile data, and the IgG diffusivity within the tissue void was estimated to be 2 x 10(-7) cm2/s, a value much higher than that published by other groups. We also demonstrate from our previous data that convection of IgG through tissue dominates over diffusion at ip pressures > 2 cmH2O, but diffusion may not be negligible. Furthermore, nonsaturable binding must be accounted for in the interpretation of tissue protein concentration profiles.

Deep cervical lymph flow following the infusion of mannitol in rabbits

Jugular lymph flow of anesthetized rabbits in response to infusion of mannitol solutions differing in osmolarity were measured. Either an isotonic (310 mosmol), hypotonie (100 mosmol), or hypertonic (605 mosmol) mannitol solution was infused into either the internal carotid artery (ICA) or the right lateral ventricle (RLV). Lymph was collected continuously and measured over a 60 min preinfusion period, as well as during mannitol infusion and intermittent recovery periods. The mean peak flow rates of hypertonic infusion for the first 30 min via ICA and RLV were 2.2 ± 0.4 (12% decrease) and 5.0 ± 1.0 μl/min (72% ncrease), over those of isotonic infusates which were 2.5 ± 0.3 μl/min (via ICA) and 2.9 ± 0.5 μl/min (via RLV), respectively. In contrast, lymph flow rates of hypotonie infusate for the first 30 min via ICA and RLV were 3.9 ± 0.8 μl/min and 2.3 ± 0.4 μl/min, respectively. A decrease both in intracranial pressure and in lymph flow following hypertonic mannitol infusion via ICA were observed. However, intracranial pressure and lymph formation were increased following hypertonic infusion via RLV. The results indicate that the changes in jugular lymph flow could be affected by the changing in osmolarity of mannitol infusate.

The immune response of foetal calves

The immunological response of foetal calves to tetanus toxoid was investigated. Emphasis was placed on foetal immunocompetence and how this related to responses seen in adult cattle. The establishment of indwelling cannulas in the efferent prescapular lymphatic ducts and superficial veins of foetal calves allowed continual monitoring of cellular and humoral changes in efferent lymph and peripheral blood. Foetal calves from 195 to 253 days gestational age had the capacity to mount cell-mediated and humoral immune responses of similar character and magnitude as adult cattle to tetanus toxoid. Intravenous and subcutaneous routes of challenge with tetanus toxoid resulted in specific antibody production which peaked 26 to 31 days after vaccination. Significant tetanus toxoid-stimulated lymphocyte proliferation was present 4 to 6 weeks after vaccination with tetanus toxoid in both a foetus and an adult. After antigenic challenge lymphocytes remained the predominant cell type in efferent prescapular lymph of foetuses and cows while at the same time a marked shift to the left, characterised by band neutrophils and neutrophilic metamyelocytes occurred in peripheral blood. Lymph flow rate increased and cell concentration decreased after antigenic challenge.

Lymph flow in sheep with rapid cardiac ventricular pacing

Increases in systemic venous pressure (Pv) associated with heart failure cause an increase in microvascular fluid filtration into the tissue spaces. By removing this excess filtrate from the tissues, lymphatic vessels help to prevent edema. However, the lymphatics drain into systemic veins and an increase in Pv may interfere with lymphatic flow. To test this, we cannulated caudal mediastinal node efferent lymphatics in sheep. We used rapid cardiac ventricular pacing (240-275 beats/min) to cause heart failure for 4-7 days. Each day we determined the lymph flow rate two ways. First, we adjusted the lymph cannula height so that the pressure at the outflow end of the lymphatic was zero. After we determined the lymph flow with zero outflow pressure, we raised the cannula so that outflow pressure was equal to the actual venous pressure. We quantitated the effect of venous pressure on lymph flow rate by comparing the flow rate with outflow pressure = Pv to the flow rate with zero out low pressure. At baseline, Pv = 5.0 +/- 2.5 (SD) cmH2O and we found no difference in the two lymph flow rates. Pacing caused Pv and both lymph flow rates to increase significantly. However for Pv < 15 cmH2O, we found little difference in the two lymph flow rates. Thus increases in Pv to 15 cmH2O at the outflow to the lymphatics had little effect on lymph flow. By comparison, Pv > 15 cmH2O slowed lymph flow by 55 +/- 29% relative to the lymph flow rate with zero outflow pressure. Thus Pv values > 15 cmH2O interfere with lymph flow from the sheep caudal mediastinal lymph node.

A prospective study of transperitoneal transport in patients undergoing peritoneal dialysis.

A prospective one-year follow-up study of the functional characteristics of the peritoneal membrane was conducted in 20 peritoneal dialysis patients. Ten patients had at least one episode of peritonitis during the follow-up period. Changes in the transperitoneal transport of small solutes were evaluated by the mass transfer area coefficients (urea, creatinine, and glucose), ultrafiltration sieving coefficients (urea and creatinine), and peritoneal equilibration test results. Changes in the capacity of the peritoneal membrane to transport macromolecules were evaluated by means of albumin mass transfer rates. Finally, changes in transperitoneal water transport were evaluated by means of the ultrafiltration properties and the lymphatic flow rates. After one year of follow-up, transport of water and the investigated solutes had not changed significantly. Even episodes of peritonitis had no permanent influence on the transport function of the peritoneal membrane. The intraperitoneal residual volumes before instillation were significantly larger in patients who developed peritonitis during the follow-up period compared to patients who did not. Over a one-year period, no changes in peritoneal membrane characteristics could be demonstrated. A large residual volume of dialysate may be a marker of increased risk of getting peritonitis.

Myocardial fluid balance in acute hypertension.

We hypothesized that (1) acute arterial hypertension increases myocardial microvascular fluid filtration and (2) the combination of acute arterial hypertension and coronary sinus pressure elevation may increase myocardial microvascular filtration sufficiently to estimate the osmotic reflection coefficient of the myocardial exchange vessels. In nine mechanically ventilated dogs we cannulated the prenodal major cardiac lymph trunk. With the use of central venous phenylephrine infusion, mean arterial pressure (MAP) was raised progressively to 120, 160, and 180 mm Hg. In five dogs we additionally raised coronary sinus pressure (CSP) to 20 and 40 mm Hg. At each manipulation of MAP and/or CSP, we measured indexes of myocardial lymphatic function and lymph-to-plasma concentration ratios for total protein (CL(TP)/CP(TP) and albumin (CL(alb)/CP(alb)). Myocardial lymph flow rate (QL; microL/min) increased exponentially (QL = 10.9.e0.014.(MAP) and myocardial lymph driving pressure (PL; mm Hg) increased linearly (PL = 2.30 + 0.20 + 0.20 . MAP) following increases, whereas CL(TP)/CP(TP) and CL(alb)/CP(alb) decreases from 0.67 +/- 0.07 (SD) to 0.56 +/- 0.10 and from 0.91 +/- 0.05 to 0.75 +/- 0.11, respectively. Adding CSP elevation increased QL up to 12 times control associated with further CL(TP)/C(TP) and CL(alb)/CP(alb) decreases to 0.49 +/- 0.05 and 0.59 +/- 0.02, respectively. We conclude that hypertensive arterial pressures are, at least in part, transmitted to the myocardial microvascular exchange vessels in the intact animal leading to increased microvascular fluid filtration. However, the combination of acute arterial hypertension and coronary sinus pressure elevation is not sufficient to produce filtration independence required for myocardial osmotic reflection coefficient determination.

Interstitial fluid, plasma protein, colloid, and leukocyte uptake into initial lymphatics.

Lymphatics serve to remove from the interstitium a range of materials, including plasma proteins, colloid materials, and cells. Lymph flow rates can be enhanced by periodic tissue compression or venous pressure elevation, but little is known to what degree enhancement of lymph flow affects material transport. The objective was to examine the uptake of plasma proteins, a colloidal perflubron emulsion (LA-11063, mean particle diameter = 0.34 micron), and leukocytes into lymphatics. Prenodal collecting lymphatics in the lower hindlimb of rabbits were cannulated with and without foot massage and after elevation of venous pressure (40 mmHg). The average lymph flow rates were elevated approximately 22-fold by the skin massage but only about threefold by venous pressure elevation. Lymph-to-plasma protein concentration ratio remained unchanged by the massage but decreased significantly after venous pressure elevation. Lymph colloid concentration and leukocyte counts were elevated on average 47 and 8.5 times, respectively, by foot massage, but both decreased after venous pressure elevation. These results suggest that skin movement by massage and elevation of the venous pressure lead to opposite lymph transport kinetics of protein, colloids, and cells. Massage is more effective to enhance material transport out of the interstitium into the initial lymphatics.

Reversal of altered intestinal mucosal immunity in rats fed elemental diet by supplementation of oleic acid.

We have previously demonstrated that elemental diet (ED) induces decreased lymphocyte transport in intestinal lymph and significant changes in T cell subsets and the number of IgA-containing cells in gut-associated lymphoid tissues of rats. In order to examine whether the low fat content contributes to the induction of immunological changes in gut-associated lymphoid tissues, the effects of additional fatty acid in the ED were investigated. Rats were divided into four groups: elemental diet alone, elemental diet supplemented with 5% oleic acid (OA), elemental diet with 10% OA and conventional diet as a control. These diets were given at the same daily calorie intake for 4 weeks. The flow rate of intestinal lymph showed no significant difference between the four groups. However, lymphocyte flux as well as the percentage of CD3+ and CD4+ cells were significantly greater in the control and the 10% OA groups than in the ED and 5% OA groups. Intestinal lymph showed decreased concentrations of IgG and IgA in the ED group, whereas the addition of 10% OA significantly attenuated the decrease in these levels. In mesenteric lymph nodes, the CD4+/CD8+ ratio was significantly decreased in the ED group, but 10% OA reversed this change. Immunohistochemical analysis of the ileal mucosa showed that in the ED group the population of CD4+ cells was decreased, while the number of CD8+ cells was increased. Supplementation of OA to ED produced similar stepwise attenuation of the changes in lymphocyte subpopulations in the lamina propria, while the 10% OA group reached levels that were not statistically different from controls. In the elemental diet group, there was a significant decrease in immunoglobulin-containing cells of the IgA class in the lamina propria of the intestine. Similarly, the addition of OA induced dose-dependent recovery in the number of IgA-containing cells. These results suggest that a low dietary concentration of fat may be closely related to changes in lymphocyte transport in intestinal lymph and mucosal immunity of intestinal mucosa induced by the feeding of a long-term ED.

Lymph pump mechanics in the rabbit hind leg.

The mechanisms that govern fluid uptake by the initial lymphatics and adjustment of lymph flow rates remain to a large degree uncertain. The aim of this study was to examine how passive tissue movement contributes to lymph flow rates. Lymph fluid was collected via a cannula inserted into one of the popliteal prenodal lymphatics in the rabbit hind leg. Lymph flow rates were measured during periodic whole leg rotation and controlled oscillatory massage of the dorsal skin of the foot. Without whole leg rotation, lymph flow remained at low values (< 0.01 ml/h). Introduction of whole leg passive rotation caused a frequency-dependent increase in lymph flow rates, which were increased linearly with the log of frequency between 0.03 and 1.0 Hz. Local skin massage in the region of the initial lymphatics also led to a similar increase of lymph flow rates dependent on frequency as well as amplitude of skin displacement. Lymph flow rates during local skin massage reached a comparable order of magnitude regardless of whether the animal was alive or the heart had been arrested, suggesting that local lymph flow rates can be adjusted by periodic tissue motion independently of capillary fluid filtration pressures. The results indicate that periodic expansion and compression of initial lymphatics provide a mechanism for lymph pumping.

Rates of flow of technetium 99m--labeled human serum albumin from peripheral injection sites to sentinel lymph nodes.

The new technique of sentinel lymphadenectomy for cutaneous melanoma provided us with a unique opportunity to quantitate the rates of lymphatic flow in afferent lymphatics. Seventeen melanoma patients underwent preoperative lymphoscintigraphy with technetium 99m-human serum albumin (HSA). The time and distance between the injection site and the sentinel lymph node (LN) were recorded. By comparison, lymphatic flow rates between footpad, popliteal LN, femoral LN, and systemic blood were measured in 60 female mice (C57BL/6) after footpad injection of 99mTc-HSA. The rate of lymphatic flow to 14 axillary, four inguinal, one popliteal, and one parotid sentinel LNs averaged 10.4 +/- 7.3 cm/min. In contrast, the lymphatic flow rate between the footpad and the popliteal LN in mice (analogous to the sentinel LN in human beings) averaged 1.33 +/- 0.52 cm/min. There was a marked delay in the passage of radionuclide through the popliteal LN with consequent slowing of the rate of flow between the popliteal and femoral LNs to 0.22 cm/min. Lymphatic flow to the sentinel LN occurs rapidly from both human skin and murine footpads. This information might be helpful in planning the timing of the incision after vital blue dye injection for identifying the sentinel LN.

Cardiac surgical conditions induced by β-blockade: Effect on myocardial fluid balance

Both crystalloid and blood cardioplegia result in cardiac dysfunction associated with myocardial edema. This edema is partially due to the lack of myocardial contraction during cardioplegia, which stops myocardial lymph flow. As an alternative, acceptable surgical conditions have been created in patients undergoing coronary artery bypass operations with esmolol-induced minimal myocardial contraction. We hypothesized that minimal myocardial contraction during circulatory support using either standard cardiopulmonary bypass (CPB) or a biventricular assist device would prevent myocardial edema by maintaining cardiac lymphatic function and thus prevent cardiac dysfunction. We placed 6 dogs on CPB and 6 dogs on a biventricular assist device and serially measured myocardial lymph flow rate and myocardial water content in both groups and preload recruitable stroke work only in the CPB dogs. In all dogs we minimized heart rate with esmolol for 1 hour during total circulatory support. Although myocardial lymph flow remained at baseline level during CPB and increased during biventricular assistance, myocardial water accumulation still occurred during circulatory support. However, as edema resolved rapidly after separation from circulatory support, myocardial water content was only slightly increased after CPB and biventricular assistance, and preload recruitable stroke work was normal. Our data suggest that minimal myocardial contraction during both CPB and biventricular assistance supports myocardial lymphatic function, resulting in minimal myocardial edema formation associated with normal left ventricular performance after circulatory support. The concept of minimal myocardial contraction may be a useful alternative for myocardial protection, especially in high-risk patients with compromised left ventricular function.

Lymphatic absorption of retinol in young, mature, and old rats: influence of dietary restriction.

Earlier studies have shown that hepatic vitamin A stores increase with age and that rats subjected to life-long dietary restriction (DR) have greater hepatic retinoid concentrations than ad libitum-fed rats. It was suggested that these changes may be attributed to altered intestinal absorption, and so we measured retinol absorption in 3, 12, and 22 month-old female Sprague-Dawley rats fed ad libitum (AL) or a restricted diet (40%) enriched (DR+) or not (DR) with vitamins and minerals. An in vivo model was used and lymph collected from the mesenteric duct while rats were infused a micellar solution containing [3H]retinol into the proximal duodenum. Aging significantly decreased lymph flow, and at all ages DR and DR+ rats exhibited a higher flow than age-matched AL rats. Absorption of retinol was not significantly modified by age in AL and DR+ rats. However, in the DR group, there was a marked decrease in absorption between 3 and 12 months of age. Retinol absorption was significantly higher in 12 and 22 month-old DR+ rats than in age-matched AL rats, a finding that may be explained by both higher lymph flow rate and higher long-term vitamin A intake per body weight. In conclusion, the increased content of vitamin A in the livers of older AL rats is not associated with changes in intestinal absorption. In DR rats, however, retinoid accumulation in the liver may be explained by increased intestinal absorption of the vitamin, though other mechanisms may be involved. A possible explanation may be a decreased output of retinol from the liver as a result of lower metabolic needs. The lower serum vitamin A concentrations observed in DR rats would tend to support this hypothesis.

The lymphatic circulation plays a dynamic role in blood volume and plasma protein restitution after hemorrhage.

The purpose of this study was to determine the contribution of the lymphatic circulation to blood volume and plasma protein restitution after hemorrhage. Splenectomized sheep were prepared with thoracic duct and vascular catheters. The day after surgery, thoracic duct lymph flow, thoracic duct lymph protein, plasma protein, mean arterial pressure, and blood volume were measured. After 12 h, awake sheep were either bled 25% of blood volume over 5 min (HEM; n = 6) or observed (SHAM; n = 5) and measurements were recorded for 48 h. In HEM, the thoracic duct protein return rate and thoracic duct lymph flow transiently decreased (0-.5 h) but were then equal to or greater than that in SHAM. In HEM, there was restitution of both blood volume and plasma protein mass approximately 12 h after hemorrhage. Both thoracic duct lymph flow and protein return rate are significant contributors to blood volume and plasma protein restitution after hemorrhage. These findings and the prior demonstration by the authors that lymphatic vessel pumping is increased after hemorrhage suggest a dynamic role for the lymphatic circulation in blood volume homeostasis after hemorrhage.

Changes in left thoracic duct lymph flow during progressive anemia in the ovine fetus

OBJECTIVE: The purpose of this study was to evaluate the extent to which increased lymph flow can return fluid and protein to the circulation in the chronically anemic fetus. STUDY DESIGN: Thoracic duct lymph flow rate over a range of outflow pressures was measured in 8 near-term fetal sheep 4 to 5 days after surgery and daily thereafter for 5 days. After each day's study 60 to 150 ml of blood was withdrawn at a rate of 1 ml per minute. Regression analysis was used to establish the lymph flow function curve. Lymph and plasma protein concentrations and lymph flow rate were compared by analysis of variance for repeated measures. RESULTS: As the hematocrit was reduced from 34.6% ± 1.3% (mean ± SE) to 14.4% ± 1.0%, thoracic duct lymph flow increased from 0.12 ± 0.01 to 0.28 ± 0.02 ml/min/kg. Plasma total protein concentration did not change, lymph protein concentration fell (2.6 ± 0.1 to 2.4 ± 0.1 gm/dl), and the difference between plasma and lymph protein concentrations increased (1.04 ± 0.05 to 1.34 ± 0.10 gm/dl). Protein returned to the circulation increased from 11.5 ± 0.3 to 23.7 ± 1.5 mg per minute. Central venous pressure did not change and remained less than the breakpoint pressure. Although the plateau lymph flow rate increased, neither the breakpoint or stopflow pressures of the lymph flow function curve were altered. CONCLUSIONS: Fetal lymph flow and thereby capillary filtration increased progressively as anemia became more severe. The increase in lymph flow did not appear to be limited by outflow pressure. By returning protein to the circulation, an increase in thoracic duct lymph flow helped to limit expansion of extravascular fluid volume during chronic fetal anemia. (AM J OBSTET GYNECOL 1996;174:1469-76.)

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

Studies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferon-gamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

The lymphatic absorption of fatty acids and output of phospholipids are lowered by estrogen replacement in ovariectomized rats

The lymphatic absorption of fatty acids and output of lipids during intraduadenal lipid infusion were compared in Sprague-Dawley ovariectomized rats with (OXE) and without (OXP) estradiol implants. A time-release estradiol pellet (25 μg/day/rat) was implanted subcutaneously in the OXE rats and a placebo pellet in OXP rats. At 4 weeks, the rats were fitted with lymph cannula and infused at 3.0 ml/hr via a duodenal catheter with a lipid emulsion containing 3.2 μCi 14C-linoleic acid ( 14C-LA), 171 μmol LA, 488 μmol triolein, 520 μmol sodium taurocholate, and 1.5 μmol α-tocopherol in 24 ml phosphate buffered saline (pH 6.4). Lymph was collected at hourly intervals for 8 hours via a mesenteric lymph cannula. The average rate of lymph flow was reduced in OXE (1.4 ml/hr), compared with that of OXP rats (2.2 ml/hr). The total cumulative absorption of 14C-LA during the 8-hr period, as expressed in % dose, was significantly lower in OXE (26.9 ± 5.2%) than in OXP rats (33.6 ± 4.0%). The lymphatic outputs of fatty acids (16:0, 18:0, 18:1, 18:2, and 18:3) also were significantly reduced in OXE rats. The amount of 14C-LA absorbed into the lymph were highly correlated (r = 0.85, P < 0.05) with the amount of phospholipid (PL) released. The results provide the first evidence that the rate of lymphatic absorption of lipids is reduced by estrogen replacement in ovariectomized rats. This may be caused by a limited availability of PL to the enterocyte during chylomicron formation.

Thoracic duct lymph flow responses to hemorrhage in the ovine fetus.

Blood volume returns toward normal after hemorrhage much more rapidly in the fetus than in the adult due to a rapid entry of fluid and plasma proteins into the fetal circulation. One potential source of fetal fluids and plasma proteins is the lymphatic system, since basal lymph flow rate and interstitial protein concentration are high in the fetus. Furthermore, studies in adults suggest that lymph flow rate may increase following hemorrhage. To test the hypothesis that hemorrhage induces an increase in lymph flow in the fetus, 15 late-gestation ovine fetuses underwent left thoracic duct catheterization with low-resistance catheters and were studied 5 or more days after surgery at 134 +/- 1 (SE) days gestation. The protocol included three successive 30-min periods: control, hemorrhage, and recovery. During the first 5 min of the hemorrhagic period, 61 +/- 4 ml of fetal blood were removed. The blood was reinfused over the first 5 min of the recovery period. After the hemorrhage, fetal arterial pressure, venous pressure, and heart rate decreased (analysis of variance, P < 0.001). These variables significantly increased above basal levels following blood reinfusion. Fetal hematocrit (P < 0.001) and plasma protein concentration (P < 0.05) also decreased after the hemorrhage and returned to control values after the reinfusion. Fetal lymph flow rate was 0.55 +/- 0.06 (SE) ml/min before the hemorrhage and decreased by a maximum of 30.3 +/- 6.3% (P < 0.001) at 8 min after the end of the hemorrhage. Lymph flow rate was reduced by an average of 19.1 +/- 6.6% during the hemorrhagic period and returned to prehemorrhage levels following blood reinfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Normothermic Continuous Antegrade Blood Cardioplegia Does Not Prevent Myocardial Edema and Cardiac Dysfunction

Normothermic continuous blood cardioplegia (BC) has been proposed to completely protect the myocardium during cardiac surgery. However, previous work from our laboratory suggests that BC could cause myocardial edema that produces cardiac dysfunction. The purpose of this present study was to evaluate the impact of BC on myocardial fluid balance and left ventricular function. In 11 dogs, myocardial water content (MWC) was determined by microgravimetry. Myocardial lymph flow rate was measured after cannulation of the major prenodal cardiac lymphatic. Preload recruitable stroke work (PRSW) was calculated by sonomicrometry and micromanometry. The dogs were placed on normothermic cardiopulmonary bypass (CPB), and BC was delivered at either 80 to 90 mm Hg (BChigh; n = 6) or 40 to 50 mm Hg (BClow; n = 5) for 1 hour. Coronary sinus lactate and oxygen saturation monitoring demonstrated ischemia avoidance. BC was associated with substantial myocardial lymph flow rate decrease (P < .05) and myocardial edema development in both groups. MWC increased from 76.0 +/- 1.9% to 79.2 +/- 1.7% (P < .05) after 10 minutes of BChigh and from 75.9 +/- 0.6% to 78.9 +/- 1.4% (P < .05) after 30 minutes of BClow. PRSW decreased to 63 +/- 19% (BChigh) and 69 +/- 15% of control (BClow) at 30 minutes after CPB (P < .05). Myocardial lymph flow rate increases of threefold to fourfold that of control (P < .05) resulted in significant myocardial edema reduction associated with PRSW improvement to 71 +/- 17% (BChigh) and to 78 +/- 11% (BClow) at 2 hours after CPB. We conclude that BC is associated with compromised cardiac function despite ischemia avoidance. This cardiac dysfunction is due to myocardial edema caused by the combination of increased myocardial microvascular fluid filtration and decreased myocardial lymph flow rate during BC.

Mechanism of colloidal particle uptake into the lymphatic system: basic study with percutaneous lymphography.

To examine the extracellular (dispersed particles) and intracellular (phagocytosed particles) colloidal particle transport from subcutaneous tissue into the lymphatic system. Perfluorocarbon emulsions LA11063 (mean particle diameter, 0.34 micron) and ZY12149 (mean particle diameter, 0.06 micron) were individually injected into the dorsal skin of the hind foot of rabbits. Lymph flow rates and particle concentrations were determined in prenodal lymph fluid after injection, with and without massage of the skin over the injection site. In the first 24 hours after injection, extracellular colloid flux was substantially larger than intracellular flux. Lymph flow rates and colloid concentrations increased substantially with massage. Extracellular LA11063 flux was smaller than ZY12149 flux, whereas intracellular LA11063 flux exceeded ZY12149 flux. Transport of colloids into lymphatic vessels is dependent on particle size. Both extracellular and intracellular pathways are utilized. External tissue movement contributes substantially to the rate of particle uptake via both pathways.

Microvascular permeability and endothelial cell morphology associated with low-flow ischemia/reperfusion injury in the equine jejunum

SUMMARY Microvascular permeability of the jejunum of clinically normal equids and microvascular permeability associated with 60 minutes of ischemia (25% baseline blood flow) and subsequent reperfusion were investigated. Eight adult horses were randomly allotted to 2 equal groups: normal and ischemic/reperfusion injury. Lymphatic flow rates, mesenteric blood flow, and lymph and plasma protein concentrations were determined at 15-minute intervals throughout the study. Microvascular permeability was determined by estimates of the osmotic reflection coefficient, which was determined when the ratio of lymphatic protein to plasma protein concentration reached a constant minimal value as lymph flow rate increased (filtration-independent lymph flow rate), which occurred at venous pressure of 30 mm of Hg. Full-thickness jejunal biopsy specimens were obtained at the beginning and end of each experiment, and were prepared for light microscopy to estimate tissue volume (edema) and for transmission electron microscopy to evaluate capillary endothelial cell morphology. The osmotic reflection coefficient for normal equine jejunum was 0.19 ± 0.06, and increased significantly (P &lt; 0.0001) to 0.48 ± 0.05 after the ische- mia/reperfusion period. Microscopic evaluation revealed a significant increase (P &lt; 0.0001) in submucosal and serosal volume and capillary endothelial cell damage in horses that underwent ischemia/reperfusion injury. Results indicate that ischemia/re-perfusion of the equine jejunum caused a significant increase in microvascular permeability.