Lymph Protein Transport Research Articles

Chronic lymph flow responses to hyperproteinemia

The long-term responses of lymph flow, lymph protein transport, and the permeability-surface area (PS) product to hyperproteinemia have been studied in conscious dogs. Plasma protein concentration (PPC) was increased by daily intravenous infusion of previously collected autologous plasma for 9 days. Lymph flow was determined by collecting lymph chronically from a lymphatic afferent to the popliteal node in the hind leg. Compared with the average value during the normal-PPC period, the following changes occurred during 10 days of high PPC: lymph flow decreased from 12.3 +/- 1.1 to 3.8 +/- 0.6 microl/min, lymph protein transport decreased from 241 +/- 24 to 141 +/- 21 microg/min, PS product decreased from 4.7 +/- 0.5 to 3.0 +/- 0.5 microl/min, PPC increased from 7.1 +/- 0.1 to 8.8 +/- 0.4 g/dl, lymph protein concentration increased from 1.9 +/- 0.1 to 3.8 +/- 0.1 g/dl, plasma colloid osmotic pressure increased from 18. 6 +/- 0.8 to 24.2 +/- 2.1 mmHg, and lymph colloid osmotic pressure increased from 4.8 +/- 0.2 to 10.4 +/- 0.7 mmHg. In conclusion, long-term hyperproteinemia in dogs resulted in chronic decreases in lymph flow, lymph protein transport, and the PS product and chronic increases in lymph protein concentration and lymph colloid osmotic pressure. The marked decrease in lymph flow during hyperproteinemia decreased lymph protein transport and thus contributed to the increase in lymph protein concentration. In addition, the decreases in PS product and lymph protein transport suggest that transcapillary protein flux decreases during hyperproteinemia.

Chronic lymph flow and transcapillary fluid flux during angiotensin II hypertension

The roles of the transvascular fluid flux and lymph flow in the distribution of extracellular fluid volume during angiotensin II (ANG II) hypertension were evaluated in 11 conscious dogs. Similarly, the factors regulating the distribution of plasma protein across the microvasculature were assessed. By the second day of ANG II infusion, the thoracic duct lymph flow had increased 58% above control, transcapillary fluid flux had increased 45%, and plasma volume, sulfate space, and interstitial fluid volume remained close to control. In addition, the thoracic duct lymph protein transport had increased 34%, and the accompanying increase in transcapillary protein flux prevented any change in plasma protein mass. Also, at this time, the lymph flow and protein transport from subcutaneous tissue in the hind limb were not increased, and the permeability-surface area product of this region decreased 40%. The origin of the increased thoracic duct lymph flow on day 2 probably was from the splanchnic bed. In conclusion, the increased lymph flow during ANG II hypertension compensated for the increase in transcapillary fluid flux, thus preventing edema formation.

Chronic transvascular fluid flux and lymph flow during volume-loading hypertension

The chronic roles of the transcapillary fluid flux and lymph flow in the distribution of extracellular fluid volume during volume-loading hypertension were investigated in five conscious dogs. Similarly, the distribution of plasma proteins across the microvasculature was evaluated. During the early phases of volume-loading hypertension the fluid balance was positive, which caused the extracellular fluid volume and the plasma volume to increase 25 and 15%, respectively. The thoracic duct lymph flow more than doubled, but the increase in transcapillary fluid flux was even greater. Therefore the interstitial fluid volume increased 30%. This fluid shift from the vasculature into the interstitium probably prevented an even greater rise in arterial pressure. In addition, the transcapillary protein flux more than doubled, but the accompanying increase in lymph protein transport prevented any change in plasma protein mass. During the latter part of the saline-infusion period, the lymph flow declined toward its control, which caused a net transfer of fluid into the interstitium. In conclusion, the transcapillary fluid flux and lymph flow play significant roles in extracellular fluid volume distribution.

Endotoxemia causes increased lung tissue lipid peroxidation in unanesthetized sheep.

Our purpose was to determine whether lipid peroxidation of lung tissue, a reflection of O2 radical injury, occurs with endotoxin, and whether the degree of tissue change corresponds with the degree of increased protein permeability. Unanesthetized adult sheep with lung lymph fistulas were given Escherichia coli endotoxin at a dose of 2 micrograms/kg (n = 34). Tissue lipid peroxidation was measured using the thiobarbituric acid assay for malondialdehyde (MDA). The MDA content of lung tissue in nanomoles per gram increased from a control value of 48 +/- 8 to 98 +/- 18 at 5 h postendotoxin (2 micrograms/kg), whereas lung lymph protein transport (Cp), was increased 3- to 4-fold. The MDA content returned to base line with Cp by 24 h postendotoxin. Six sheep given endotoxin were pretreated with 12.5 mg/kg of ibuprofen, and six were infused with dimethylthiourea (DMTU) 0.75 g/kg. With ibuprofen, Cp was only increased 2.5- to 3-fold and MDA was increased to 69 +/- 15 nmol/g. With DMTU, the increase in Cp was comparable to that with endotoxin alone, as was the MDA of lung tissue with a value of 92 +/- 12 nmol/g. The correlation of tissue MDA with Cp in all animals was 0.83. We conclude that lipid peroxidation occurs in lung tissue after a moderately severe endotoxin injury with the degree of change corresponding to the degree of increased Cp.

Effect of hydroxyl radical scavenging on endotoxin-induced lung injury

The release of oxygen radicals, in particular the hydroxyl radical, from sequestered neutrophils produces acute lung injury after a number of insults. Our purpose was to determine whether hydroxyl radical, OH., is responsible for the lung injury from endotoxin characterized by (1) pulmonary leukostasis, (2) increased thromboxane production leading to pulmonary hypertension and hypoxia, and (3) increased protein permeability. This hypothesis was tested by infusion of a selective OH. scavenger, dimethyl thiourea (0.75 gm/kg), into unanesthetized sheep before endotoxin and comparison of the response to that seen with endotoxin alone. Pulmonary vascular integrity was measured by the use of lung lymph flow, QL, and lymph protein transport. Thromboxane A2 was measured as TxB2 and prostacyclin as 6-keto-PGF1 alpha. We found no difference in the degree of leukopenia and hypoxia after endotoxin or the levels of TxB2, 6-keto-PGF1 alpha, and pulmonary hypertension with dimethyl thiourea, compared with endotoxin alone. The permeability injury was also identical, with a twofold to threefold increase in protein-rich lymph seen in both groups. It appears that OH. does not play a major causative role in either phase of endotoxin lung injury.

Blockade of histamine-mediated increases in microvascular permeability by H 1- and H 2-receptor antagonists

The receptor mechanisms by which histamine increases microvascular fluid and protein efflux were studied in the canine forelimb perfused at constant flow. Skin lymph flow, protein concentration, and protein transport (flow × concentration) were examined during the intraarterial infusion of histamine alone and during the simultaneous infusion of histamine and the histamine antagonists tripelennamine or cimetidine. The infusion of histamine alone at 1.4 μg base/min resulted in a significant decrease in forelimb perfusion pressure and skin small-artery pressure and a small but significant increase in skin small-vein pressure. Histamine produced a 2 1 2 - fold increase in lymph flow, a 2-fold increase in lymph protein concentration, and a 5-fold increase in lymph protein transport. Infusion of this same dose of histamine during the simultaneous infusion of the H 1-receptor antagonist tripelennamine (10 μg/min) produced essentially the same changes in forelimb vascular pressures but failed to produce significant changes in lymph flow, lymph protein concentration, or lymph protein transport. Similarly, the infusion of cimetidine (250 μg/min), an H 2-receptor antagonist, concurrent with the infusion of histamine elicited no significant changes in lymph parameters but the fall in arterial pressures was attenuated. Since either an H 1- or an H 2-receptor antagonist is capable of blocking histamine-mediated increases in lymph flow and protein concentration, these data indicate a role for both H 1 and H 2 receptors in histamine-mediated increases in microvascular permeability.

Effects of histamine and increased venous pressure on transmicrovascular protein transport

Histamine administered locally into canine forelimbs increases lymph flow, lymph protein concentration, and lymph protein transport. In this study we examined the time course of these changes and compared them to the changes produced by mechanically increasing venous pressure alone and during the infusion of histamine or acetylcholine. Intrabrachial infusion of histamine at 4 μg base/min produced 25- and 45-fold increases in lymph flow and protein transport, respectively, and a 50% increase in lymph protein concentration. These effects, however, waned with time. Qualitatively similar changes were seen with histamine infused at 16 and 64 μg base/min. Increased venous pressure alone produced 8- and 5-fold increases in lymph flow and protein transport, respectively, and decreased total protein concentration. Increasing venous pressure during histamine infusion further increased lymph flow and protein transport, which then waned with time. However, protein transport during histamine plus increased venous pressure was always greater than with the infusion of histamine alone. Increasing venous pressure during acetylcholine infusion increased lymph flow but decreased lymph protein concentration, resulting in only a small increase in total protein transport. These data indicate that the effects of histamine on protein transport are much greater than during increased venous pressure alone but that they wane with time. Increasing venous pressure during histamine infusion further increases protein transport relative to histamine alone. Histamine appears to increase microvascular efflux of protein, at least in part, through a mechanism which is sensitive to changes in microvascular pressure.

The effects of cholecystokinin and cholecystokinin-octapeptide on intestinal lymph flow in the rat.

Intravenous cholecystokinin and its synthetic C-terminal octapeptide were found to cause a transient augmentation of intestinal lymph flow in the rat. Concomitant increase in lymph protein transport suggests that this reflects the increase in intestinal blood flow which is known to occur in response to these agents.

Distribution and circulation of extracellular fluid and protein during different states of hydration in the cat.

1. Determinations of plasma volume (PV) and circulating protein in 13 anaesthetized cats before and after dehydration by deprivation of water for 48 h revealed an 11.5% decrease of PV and a 13.5% decrease of circulating protein, the plasma protein concentration and the albumin/globulin ratio remaining essentially constant. Extracellular fluid volume (ECFV) was reduced by 13.8% in 9 dehydrated animals as compared to 10 control animals. 2. The fractional disappearance rate of radio albumin revealed that half a pool of albumin is exchanging with the extravascular space in 10 h in control animals as well as in dehydrated animals. The observation that lymph flow and lymph protein transport from the thoracic duct were closely correlated with the state of filling of the interstitial space explains why half a pool of plasma albumin was returned to the blood stream in 16.5 h in dehydrated animals as compared to 10 h in controls. The reduction of plasma albumin due to dehydration was calculated to result from the disturbance of the dynamic equilibrium between transcapillary albumin shift and lymphatic return. 3. During rehydration by saline infusion, dehydrated animals kept larger percentages of the infused fluid inside the intravascular space demonstrating a decrease of net transcapillary fluid shift. The increase of lymph flow during infusion was shown to be closely correlated with the filtration rate. There was an increase of transcapillary protein shift and a decrease of transport rates for lymph protein during infusion.