Thoracic Duct Lymph Flow Rate Research Articles

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 After each day's study 60 to 150 ml of blood was withdrawn at a rate of 1 ml per minute.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.)

Blood volume response to drainage of left thoracic duct lymph in the ovine fetus

Although it is known that left thoracic duct lymph flow rate in the ovine fetus is several times that in the adult relative to body weight, the role of the lymphatic system in maintaining fetal blood volume has not been explored. In the present study, the left thoracic lymph duct was drained without return to the fetal circulation in 10 chronically catheterized animals for 7 h. Four experiments in which the lymph was returned to the circulation served as control. During the 7-h drainage, the total volume drained was 174.4 +/- 19.6 ml. Thoracic duct lymph flow rate decreased gradually and averaged 22.2 +/- 3.4% (SE) below control at 6-7 h compared with a small increase in the control experiments (analysis of variance: P = 0.0013 comparing 2 groups). Fetal blood volume decreased (P < 0.0001) by 8.2 +/- 1.1% at 3 h because of a decrease in plasma volume with a further small decrease in blood volume to 9.7 +/- 0.9% below normal at 7 h. The decreases in blood volume at 1, 3, 5, and 7 h were 49.5, 40.2, 24.6, and 21.7%, respectively, of the volume of lymph that was drained. Fetal vascular pressures and heart rate did not change significantly. Although protein concentrations in plasma (-6.8 +/- 1.3%) and lymph (-7.5 +/- 2.1%) decreased, the lymph-to-plasma protein concentration ratio remained constant at 0.72 +/- 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Maximal lymph flow in the ovine fetus

This study was designed to determine the maximal left thoracic duct lymph flow rate in late-gestation ovine fetuses. Chronically catheterized sheep fetuses (n = 8) with indwelling left thoracic lymph duct and vascular catheters were studied > or = 5 days after surgery at 136 +/- 1 (SE) days' gestation. To increase lymph flow rate, 4 L of warm lactated Ringer's solution were infused intravenously into the fetus over 4 hours, because this causes mild edema as determined ultrasonographically. During a 1-hour preinfusion period lymph flow rate was 0.53 +/- 0.06 ml/min. During the infusion increases occurred in fetal arterial (7.6 +/- 1.0 mm Hg) and venous (2.4 +/- 0.3 mm Hg) pressures (p < 0.001). Lymph flow rate increased and reached a plateau after 1 hour at 339% +/- 30% of preinfusion values (p < 0.001). When the infusion was terminated, fetal arterial and venous pressures rapidly returned to preinfusion levels. Lymph flow rate gradually decreased during the first 30 minutes and stabilized at 97% +/- 17% above control during the subsequent 30 minutes. Analysis of lymph flow rate as a function of outflow pressure revealed that the increases in flow occurred because of an upward shift in the plateau flow rate with no change in the stop-flow pressure. (1) Fetal left thoracic duct lymph flow rate can increase significantly above basal values and therefore is an important safety factor against fetal edema formation. (2) The maximal lymph flow rate appears to be 3.4 times normal when venous pressure is elevated and two times normal when venous pressure is normal.

Intestinal lymphatic pressure increases during intravenous infusions in awake sheep.

Intravenous fluid infusions cause increased venous pressure and increased lymph flow throughout the body. Together the increased lymph flow and increased venous pressure (the outflow pressure to the lymphatic system) should increase the pressure within the postnodal intestinal lymphatics. To test this, we measured the pressure in postnodal intestinal lymphatics and the neck vein pressure in five awake sheep. At baseline, the neck vein pressure was 1.2 +/- 1.5 (SD) cmH2O and the lymphatic pressure was 12.5 +/- 1.7 cmH2O. When we infused Ringer solution intravenously (10% body weight in approximately 50 min), the neck vein pressure increased to 17.3 +/- 0.9 cmH2O and the lymphatic pressure increased to 24.6 +/- 3.8 cmH2O (both P < 0.05). In two additional sheep, the thoracic duct lymph flow rate increased from 0.8 +/- 0.4 ml/min at baseline to 5.5 +/- 2.0 ml/min during the infusions. Our results show that postnodal intestinal lymphatic pressure may increase substantially during intravenous fluid infusions. This is important because increases in postnodal lymphatic pressure may slow lymph flow from the intestine.

Thoracic duct lymph flow in fetal sheep with increased venous pressure from electrically induced tachycardia.

The intent of this study was to investigate thoracic duct lymph flow, as it is related to the development of hydrops fetalis during rapid atrial pacing. We studied 6 fetal sheep at 128 +/- 6 days of gestation who had chronically placed thoracic duct catheters, aortic and superior vena cava catheters, and atrial pacing electrodes. Atrial pacing at 317 beats/min caused an elevation in central venous pressure from a baseline value of 3 Torr to 7 Torr without affecting pH, arterial blood gas tensions, aortic blood pressure, total protein concentration, or colloid osmotic pressure, although there was a small rise in hematocrit. The thoracic duct lymph flow rate at baseline was 41 +/- 6 ml/h. After atrial pacing for 6 h, the lymph flow rate as measured over at least three consecutive 10-min intervals, and presumably the transvascular fluid filtration rate, increased to 67 +/- 7 ml/h if it was collected at an outflow pressure of 3 Torr, equal to the venous pressure prior to the onset of atrial pacing. However, if the lymph was collected instead at an outflow pressure of 7 Torr, equal to the actual venous pressure measured with rapid atrial pacing, then the lymph flow rate diminished to 48 +/- 5 ml/h. This difference in lymph flow secondary to the increase in venous pressure could account for a maximum of 19 ml/h of edema that accumulates in fetal interstitium and body cavities with atrial pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of outflow pressure upon thoracic duct lymph flow rate in fetal sheep.

Edema develops when lymph does not return to the venous circulation at a rate equal to the rate of capillary filtration. Fetal sheep develop edema as well as an increased central venous pressure while undergoing atrial pacing at 320 beats per min. We hypothesized that the increased central venous pressure augmented the appearance of fetal edema by impairing the return of thoracic duct lymph to the venous circulation. To investigate this hypothesis, we studied the effect of outflow pressure upon thoracic duct lymph flow in 10 unanesthetized fetal sheep who had low resistance lymph catheters placed in the cervical thoracic duct near its junction with the left jugular vein. After the ewe and fetus recovered for 5 d, we altered the outflow pressure of the lymph catheter by adjusting its height with respect to amniotic fluid pressure and measured the resultant change in thoracic duct lymph flow rate. We found that lymph flow rate was constant over the range of outflow pressures (central venous pressures) normally encountered but decreased in a linear fashion at pressures greater than 0.68 kPa (5.1 torr). Lymph flow stopped at an outflow pressure of 2.40 kPa (18 torr). The data points are best fit by two lines obtained by a piecewise linear regression rather than a single line obtained from a linear regression. We conclude that fetal thoracic duct lymph flow is sensitive to elevations in outflow pressure. Lymph flow begins to diminish at outflow pressures corresponding to central venous pressures commonly encountered in pathologic conditions and may augment the appearance of fetal edema.

Long-term vascular volume expansion maintains elevated thoracic duct lymph flow

OBJECTIVE: To investigate the mechanisms responsible for edema seen during pregnancy, we tested whether lymph vessels are able to pump high volumes over long periods of time. STUDY DESIGN: In six chronically catheterized nonpregnant ewes, we examined left thoracic duct lymph flow rate and fluid balance responses to the administration of a balanced isotonic solution at a rate of 1 L/hr for 20 hours. Because estrogen administration decreases lymphatic contractility against outflow pressure, we also administered conjugated estrogens (Premarin) during the last 3 hours of the fluid infusion (experimental time 17 to 20 hours). RESULTS: After volume loading for 16 hours, the mean ± SEM lymph flow rate, blood volume, and arterial pressure rose 100% ± 26%, 20% ± 2.3%, and 16% ± 8.1%, respectively. Vascular compliance decreased significantly and, as evidenced by a lack of body weight changes, interstitial fluid volume failed to change ( p < 0.05, analysis of variance). The transcapillary oncotic pressure difference increased by 2 mm Hg; venous pressure increased by 5.2 mm Hg. These data suggest that transcapillary forces favored fluid movement into the interstitium. Lymph flow rate remains elevated after blood volume expansion to a level similar to that described during pregnancy in sheep. A transient decrease in urinary output (∼20%) occurred with no changes in lymph flow rate, arterial pressure, or blood volume. CONCLUSION: Lymph flow rate is able to compensate for the increased capillary filtration observed during prolonged blood volume expansion.

Left thoracic duct lymph flow responses to angiotensin II or atrial natriuretic factor infusion in the ovine fetus

In the ovine fetus it is known that left thoracic duct lymph flow rate relative to body weight is four to five times adult levels, but it is not known whether the circulating hormones modulate fetal lymph flow. To explore this, we intravenously infused either angiotensin II (10 to 400 ng/min, n = 8) or atrial natriuretic factor (500 to 1000 ng/min, n = 8) into chronically catheterized fetal sheep for 30 minutes. Significant increases occurred in fetal arterial (p < 0.0001) and venous (p = 0.018) pressures during the angiotensin II infusion, and thoracic duct lymph flow rate underwent a dose-dependent increase (r = 0.888, p = 0.0033). With termination of the angiotensin II infusion, fetal vascular pressures rapidly returned to control levels, and lymph flow fell from 18.8% ± 10.1% (mean ± SE) above control to 13.7% ± 7.7% below preinfusion levels (p < 0.01 ). During the atrial natriuretic factor infusion, fetal arterial pressure and circulating blood volume decreased significantly (p < 0.01 ), whereas thoracic duct lymph flow was unchanged. After termination of the atrial natriuretic factor infusion, fetal arterial pressure returned toward control, blood volume remained reduced, and lymph flow rate underwent a transient rise to 35.6% ± 15.7% (p < 0.05) above control levels. These data suggest that angiotensin II and atrial natriuretic factor have significant but opposite effects on fetal thoracic duct lymph flow rate, with angiotensin II stimulating and atrial natriuretic factor suppressing lymph flow. (AM J OBSTET GYNECOL 1991;165:1607-13.)

Effect of thoracic duct drainage on hydrostatic pulmonary edema and pleural effusion in sheep

Positive end-expiratory pressure (PEEP) increases central venous pressure, which in turn impedes return of systemic and pulmonary lymph, thereby favoring formation of pulmonary edema with increased microvascular pressure. In these experiments we examined the effect of thoracic duct drainage on pulmonary edema and hydrothorax associated with PEEP and increased left atrial pressure in unanesthetized sheep. The sheep were connected via a tracheostomy to a ventilator that supplied 20 Torr PEEP. By inflation of a previously inserted intracardiac balloon, left atrial pressure was increased to 35 mmHg for 3 h. Pulmonary arterial, systemic arterial, and central venous pressure as well as thoracic duct lymph flow rate were continuously monitored, and the findings were compared with those in sheep without thoracic duct cannulation (controls). At the end of the experiment we determined the severity of pulmonary edema and the volume of pleural effusion. With PEEP and left atrial balloon insufflation, central venous and pulmonary arterial pressure were increased approximately threefold (P less than 0.05). In sheep with a thoracic duct fistula, pulmonary edema was less (extra-vascular fluid-to-blood-free dry weight ratio 4.8 +/- 1.0 vs. 6.1 +/- 1.0; P less than 0.05), and the volume of pleural effusion was reduced (2.0 +/- 2.9 vs. 11.3 +/- 9.6 ml; P less than 0.05). Our data signify that, in the presence of increased pulmonary microvascular pressure and PEEP, thoracic duct drainage reduces pulmonary edema and hydrothorax.

Estrogen effects on lymph flow as a function of outflow pressure in ewes

The purpose of the present study was to assess whether acute estrogen administration decreased the lymphatic vessel's "pumping" ability. An additional goal was to assess whether estrogen affected the capillary filtration (used here as the total transfer of fluid and protein across the capillaries evidenced by the thoracic duct lymph flow rate). We reasoned that if estrogen administration decreases the lymph pumping ability against outflow pressure, then this phenomenon could help to explain the interstitial fluid retention seen during chronic estrogen. In six nonpregnant ewes we studied the thoracic lymph flow rate measured at different outflow pressures, before and after the acute administration of 50 mg of Premarin (conjugated estrogenic hormones). We also continuously determined arterial and venous pressures and heart rate. The arterial pressure declined from a mean of 99 +/- 0.33 (SE) mmHg to 95.4 +/- 0.2 mmHg (P less than 0.05) after the administration of estrogen. Heart rate increased from 88.5 +/- 0.8 to 111.3 +/- 1.2 beats/min (P less than 0.01). Venous pressure, plasma and lymph protein concentrations, and hematocrit did not change significantly (P greater than 0.1). Lymph flow rate declined progressively when measured against positive outflow pressure, whereas it remained stable when measured against negative pressure. Lymph flow rate during negative outflow pressure was higher after the administration of estrogen 0.044 +/- 0.002 vs. 0.032 +/- 0.002 ml.min-1.kg-1 for the control period (P less than 0.05). The calculated outflow pressure at which lymph flow rate became zero was similar for the period before or after the estrogen administration (P greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of outflow pressure and vascular volume loading on thoracic duct lymph flow in adult sheep

Studies have shown that lymph flow rate from several tissues depends on the pressure at the outflow end of the lymphatics. The left thoracic lymph duct is the largest lymphatic vessel and it transports a majority of the body's lymph. We varied outflow pressure for the left thoracic lymph duct independent of venous pressure in six unanesthetized, nonpregnant adult ewes with chronic lymphatic and venous catheters. When outflow pressure was negative, the thoracic duct lymph flow rate was independent of outflow pressure and averaged 0.040 +/- 0.004 (SE) ml.min-1.kg body wt-1. Lymph flow began to decrease with increasing outflow pressure only when outflow pressure was significantly greater than venous pressure. Above this breakpoint, lymph flow decreased linearly with outflow pressure and ceased at an outflow pressure of 25.6 +/- 4.2 mmHg. After vascular volume loading with lactated Ringer solution, steady-state thoracic duct lymph flow increased to 351 +/- 54% of control and was independent of outflow pressure when outflow pressure was negative. As outflow pressure was elevated, lymph flow began to decrease at the same breakpoint as before volume loading, and lymph flow ceased at the same outflow pressure as before volume loading. Thus this study shows that there is a plateau where thoracic duct lymph flow rate is independent of outflow pressure. In addition venous pressure under normal or volume-loaded conditions is not an impediment to thoracic duct lymph flow in unanesthetized sheep. Large increases in venous pressure are required to totally block thoracic duct lymph flow.

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.

Fetal thoracic duct lymph flow response to intravascular saline infusion.

The left thoracic lymph duct was catheterized at the base of the neck in the sheep fetus at 123-136 days of gestation, and the lymphatic catheter was connected to a jugular vein catheter so that the lymph could return to the fetus. Lymph flow was studied 5 days after catheter implantation in the unanesthetized fetus. Basal fetal thoracic duct lymph flow rate per unit body weight averaged three times adult sheep values. After an infusion of 20 ml/kg of warmed isotonic saline into a fetal vein over 5 min, lymph flow rate increased significantly to 161 +/- 15% of control, with a peak at 8 min after termination of the infusion, and flow declined thereafter. The increased lymph volume above baseline values over 30 min averaged 5.7% of the infused volume and is similar to the adult response. Plasma and lymph protein concentrations decreased as did the lymph-to-plasma protein concentration ratio. The latter is opposite to what occurs in the adult under the same conditions. Thus the present study shows that even though the fetus has a much higher basal thoracic duct lymph flow rate than the adult, the responsiveness of the fetal lymphatic system to intravascularly infused saline is similar to that of the adult. The decrease in the lymph-to-plasma protein concentration ratio suggests that there may be differences between fetal and adult vascular-interstitial-lymphatic protein kinetics.

Thoracic duct lymph flow in pregnant sheep and response to blood volume expansion.

Left thoracic duct lymph flow rate averaged 0.077 +/- 0.003 (SD) and 0.078 +/- 0.003 ml X min-1 X kg-1 in near-term pregnant and nonpregnant sheep (P greater than 0.5). Lymph and plasma protein concentrations were unaltered in the pregnant compared with the nonpregnant animals. The thoracic duct lymph flow responses to three serial intravenous infusions of lactated Ringer solution were essentially the same in the pregnant and nonpregnant animals. Blood volume and vascular pressure changes during and after volume loading were essentially the same in both groups. In addition, terbutaline administration after volume loading caused no change in thoracic duct lymph flow rates. Thus the present study suggests that basal lymph flow rates, lymphatic function, and vascular as well as interstitial compliances are largely unaltered late in pregnancy in the sheep. In addition, beta-mimetic stimulation with terbutaline does not appear to suppress lymph flow rate.

Effects of hypotonic, isotonic, and hypertonic fluids on thoracic duct lymph flow.

To test whether whole-body lymph flow responses to vascular volume loading depend on osmolality, we measured left thoracic duct lymph flow rate and protein concentration, plasma protein concentration, plasma osmolality, hematocrit, and arterial and venous pressures in pentobarbital-anesthetized, acutely nephrectomized dogs. Hypo- (100 mosmol), iso- (309 mosmol), and hypertonic (600 mosmol) saline, isotonic lactated Ringer solution, and 5% glucose in lactated Ringer solution (580 mosmol) were infused into the jugular vein (20 ml/kg per infusion over 5 min at 30-min intervals). Changes in blood, interstitial, and cellular volumes were calculated from the infused volume and from the hematocrit and plasma osmolality. The hypotonic fluid increased lymph flow about half as much as the isotonic fluid, whereas the hypertonic fluids increased lymph flow about twice as much as the isotonic infusions. Responses appeared independent of the osmotic agent, because hypertonic NaCl was as effective as hypertonic glucose in increasing lymph flow. Responses were not altered appreciably after lowering arterial pressure by 25 mmHg. The major finding of this study is that for every condition we explored, the excess lymph flow over 30 min (ELF in ml X kg-1 X 30 min-1) correlated with the change in interstitial fluid volume (delta ISFV in ml/kg); ELF = 0.076 delta ISFV (r = 0.909). These data suggest that cellular fluid that enters the interstitium is equally effective in increasing thoracic duct lymph flow as is vascular fluid that filters into the interstitium.