Skin Lymph Flow Research Articles

The effects of tissue expansion on skin lymph flow and lymphatics: An experimental study in rabbits: Ercocen AR, Yilmaz S, Can Z. Scand J Plast Reconstr Hand Surg 32:353,1998

The effects of tissue expansion on skin lymph flow and lymphatics: An experimental study in rabbits: Ercocen AR, Yilmaz S, Can Z. Scand J Plast Reconstr Hand Surg 32:353,1998

The effects of tissue expansion on skin lymph flow and lymphatics: an experimental study in rabbits.

Histomorphological, physiological, and biomechanical changes of the skin and tissue that are being expanded have been extensively studied in the past. The purpose of this study was to investigate whether the skin lymph flow and lymphatics may be influenced during tissue expansion, and also to study different pattern of vascular supply of skin on lymph flow during tissue expansion. The skin lymph flow was quantitatively assessed by 99mTc-dextran lymphoscintigraphy, and the structure of dermal lymphatics was evaluated by histological examination in 12 rabbits. Lymphoscintigraphic results showed that lymph flow is significantly reduced both in expanded and non-expanded (sham-operated) skin. Histologically, we saw widespread lymphatic distension in both expanded and non-expanded skin. There were no quantitative differences in the number of lymphatic vessels compared with control skin. We did not see any lymphatic capillaries in the subdermal capsule of either expanded or non-expanded skin. These results show that lymphostasis has an obstructive (mechanical) aetiology, and the tissue expander itself reduces the lymph flow regardless of expansion, and interferes with the formation of new lymphatic vessels.

The Measurement of Skin Lymph Flow by Isotope Clearance—Reliability, Reproducibility, Injection Dynamics, and the Effect of Massage

The measurement of skin lymph flow was investigated using an isotope clearance technique (ICT). Multiple lymph flow determinations were undertaken in the skin of anaesthetized large white pigs to test for reproducibility, ascertain the most suitable tracer, study the influence of injection dynamics, and observe the effect of massage as a stimulus to lymph flow. Blood clearance of tracer was also investigated. Results demonstrated that lymphatic clearance is a monoexponential function with good reproducibility under controlled laboratory conditions. 99mTc-colloid (TCK17 Cis) compared favorably with 131I-human serum albumin as a tracer and both performed better than colloid gold (198Au). Lymph flow was significantly faster in one pig than in the other. No difference existed between left and right sides or between caudal and rostral sites on each flank, but clearance was significantly slower in thigh than flank skin. Sub-epidermal injections cleared faster and more consistently than either deep or subcutaneous injections. Neither injection volume nor needle tract backflow of tracer influenced results, but local massage significantly enhanced clearance. Escape of 99mTc-colloid by the blood was negligible. These results indicate that skin lymph flow can be reliably measured when conditions are controlled. Extrinsic factors such as massage strongly influence lymph flow. Greater sensitivity in detecting degrees of lymphatic insufficiency may be achieved if a standardized stimulus to lymph flow is administered during isotope clearance measurement.

Isoproterenol inhibits the increase in microvascular membrane permeability produced by bradykinin.

Bradykinin (BRADY) is hypothesized to cause the "capillary leak" syndrome in patients with sepsis, trauma, and burns. Our purpose was to determine if isoproterenol (ISO) reversed a BRADY-produced accelerated loss of intravascular fluid and protein into the interstitium of skin. An increase in microvascular permeability in canine hind paw skin was sustained by a continuous femoral artery infusion of BRADY (0.2 micrograms/kg/min). After 2 hours of BRADY, skin lymph flow (LYM FLOW microliters/min) increased nine-fold and skin lymph-to-plasma total protein concentration ratio (RTP) was substantially increased. Mean blood flow in the femoral arteries was increased four-fold by the BRADY infusion. After 2 hours of BRADY-induced increased permeability, five of the ten dogs were started on intravenous ISO (2 micrograms/min continuously) which increased heart rate from 182 +/- 15 to 222 +/- 11 beats/min. ISO reversed the increase in RTP produced by the BRADY. After 8 hours of BRADY, there was less tissue albumin in the dogs given ISO (14.5 +/- 2.0 vs. 29.5 +/- 6.6 mg/gram dry wgt, p less than 0.05 unpaired t-test). ISO can reverse the sustained increase in skin microvascular permeability produced by BRADY.

Effects of ANP on venous pressures and microvascular protein permeability in dog forelimb

Intravenous administration of alpha-atrial natriuretic peptide (ANP) produces a decrease in arterial blood pressure due to a decrease in cardiac output. The mechanism of the decrease in cardiac output is unknown but has been suggested to result from transcapillary fluid efflux caused by venoconstriction and/or increased permeability of the microvascular membrane to plasma proteins. We investigated these possibilities in the dog forelimb perfused at constant flow and prepared to measure 1) large and small vessel pressures in the two parallel skin and skeletal muscle vascular beds, and limb weight; or 2) skin lymph flow and skin lymph protein concentration. In both preparations, human ANP was injected and infused into the brachial artery. Bolus injections of ANP (0.1-0.4 micrograms) depressed perfusion pressure much less than acetylcholine or an isotonic solution of potassium chloride and did not raise small vein pressures. ANP infused at nine different rates ranging from 0.1 ng to 38.8 micrograms/min failed to influence skin and muscle small and large vein pressures, limb weight, skin lymph flow, and skin lymph protein concentration. It also failed to affect perfusion pressure and skin and muscle small artery pressures until the infusion was shut off, at which time they increased above control levels. These studies suggest that human alpha-ANP is neither a direct venous constrictor nor a potent arteriolar dilator and does not directly influence the permeability of the microvascular membrane to plasma proteins in the skin and skeletal muscle of the dog forelimb.

Hypertonic saline resuscitates dogs in endotoxin shock

In this experiment we determined if infusions of hypertonic saline (HS, 1080 Na meq/liter) could resuscitate dogs in endotoxin shock as effectively as Ringer's lactate (RL, 130 Na meq/liter). Anesthetized dogs received iv 0.5 mg/kg of Escherichia coli endotoxin, and mean arterial pressure (MAP, mm Hg) decreased from 148 ± 5 to 58 ± 14 within 30 min. To resuscitate the dogs 13 meq/kg of sodium was intravenously infused over 90 min as either a 10% body weight load of RL ( n = 5) or a 1.2% body weight load of HS ( n = 5). Both solutions produced an equivalent hemodynamic resuscitation 3 to 4 hr postinfusion with an increase in MAP (RL, 119 ± 4; HS, 108 ± 7), the restoration of cardiac outputs to baseline (RL, 2.0 ± 0.2; HS, 1.9 ± 0.3 liter/min), and similar renal inulin clearances (RL, 48 ± 16; HS, 44 ± 7 ml/min). The net fluid gain (resuscitation fluid volume infused minus urine output as percentage of body weight) was much greater in the RL group (7.2 ± 1.0%) than in the HS group (0.48 ± 0.2%). Plasma volume (PV, percentage of body weight) was measured with Evans blue dye in these splenectomized dogs. The increase in PV in the RL dogs (1.25 ± 0.04%) was slightly greater than the increase in the HS group (0.94 ± 0.13). Prenodal skin lymph was collected from both hindpaws, and the fractional increase in skin lymph flow after RL (4.5 ± 2.9) was greater than the increase in the HS group (1.7 ± 0.3). A small volume of HS can resuscitate dogs in endotoxin shock as well as an equal sodium load of RL by expanding the plasma volume with fluid that shifts to the intravascular compartment.

Interstitial albumin mass and transcapillary extravasation rate of albumin in DMBA-induced rat mammary tumours

Transcapillary extravasation rate for radio-iodinated human serum albumin (I-HSA) from plasma to interstitial fluid, interstitial albumin mass and interstitial albumin concentration have been determined in dimethyl-benz-alpha-anthracene (DMBA)-induced mammary tumours in rats. The plasma radioactivity of tracer was kept constant in awake, freely moving rats by a continuous infusion of I-HSA from 1 to 72 h after an initial priming dose. Capillary leakiness for I-HSA was calculated as the plasma equivalent volume of I-HSA located extravascularly after 1 h infusion divided by the blood volume in the tissue, i.e. as the fractional extravasation rate (FER). The experiments showed that FER was highest in tumours while intestine and skin had FER of about 70% and 25% that of tumour respectively. Heart and skeletal muscle had similar FER about 1/8 that of tumour. Interstitial albumin concentration in tumour averaged 42% of plasma albumin concentration in tumour. Intestine, heart and skeletal muscle had interstitial albumin concentrations between 34 and 37% of plasma albumin concentration while skin had an albumin concentration averaging 20% that of plasma. Lymph flow was calculated as the product of the fractional turnover rate constant for interstitial albumin and interstitial volume (extravascular 51Cr-EDTA volume) and averaged 36.7 X 10(-3) mg/g X h in tumour while intestine and heart had lymph flows of 19.1 X 10(-3) and 14.1 X 10(-3) ml/g X h respectively. In muscle and skin lymph flow was 2.4 X 10(-3) and 18.3 X 10(-3) ml/g X h respectively. It is suggested that the high interstitial fluid pressure previously observed in these tumours will contribute in maintaining interstitial volume in a steady state by opposing fluid filtration into the interstitium and maintaining a lymph flow high enough to remove excess fluid and protein from the interstitium.

Effect of norepinephrine on lymph flow and edema formation in the canine forelimb.

In the present study we sought evidence for the hypothesis that norepinephrine (NE) can cause constriction of lymph vessels in the canine forelimb perfused at constant flow. Mechanical venous compression (small-vein pressure approximately equal to 45 mmHg), intra-arterial infusion of histamine (16 micrograms base/min), and intra-arterial infusion of NE (16 micrograms base/min) caused the limbs to gain weight at similar rates due to edema formation; the first two maneuvers caused a sustained increase in skin lymph flow, but the increase in lymph flow with NE was only transient. Similar changes were seen during infusion of NE at 1 and 2 micrograms/min, and studies with radioactive microspheres indicated that NE increased capillary blood flow. When venous pressure was elevated and held constant at 45 mmHg. NE (4 micrograms base/min ia) antagonized and phentolamine (400 micrograms/min ia) potentiated the increase in skin lymph flow. Finally, NE (16 micrograms base/min ia) caused a reduction in histamine (16 micrograms base/min)-elevated skin lymph flow, despite the fact that capillary pressure was greatly increased due to active venous constriction. We conclude that intra-arterial infusion of norepinephrine in the dog forelimb perfused at constant flow causes constriction of lymphatic trunk vessels in skin, resulting in increased resistance to the flow of lymph.

The possible role of acetate in exercise hyperemia in dog skeletal muscle.

The possible role of acetate in the genesis of exercise hyperemia was studied in five series of dogs. Intraarterial infusion of an isomotic solution of sodium acetate at 0.76 ml/min in the dog forelimb decreased the resistance to flow through skeletal muscle by 48%, primarily by decreasing resistance to flow through small vessels. Skin lymph flow and lymph protein concentration were unaffected. The hindlimb of the conscious dog took up acetate at rest (A-V difference, + 58.3 +/- 19.6 nmoles/ml) and put out acetate during treadmill exercise (A-V difference, -105.6 +/- 20.12 nmoles/ml); femoral venous blood acetate concentration increased by 145 nmoles/ml (control 195 nmoles/ml). In the gracilis muscle of the anesthetized dog, simulated exercise at 0.5, 1.0 or 2.0 Hz increased acetate tissue content (72, 248 and 442 nmoles/g, respectively), output (18,899, and 1,830 nmoles/100 g/min, respectively) and venous concentration (82, 49 and 39 nmoles/ml, respectively) and changes in tissue acetate content correlated with changes in vascular resistance r = 0.75, P less than 0.001. Intraarterial infusion of an isosmotic solution of sodium acetate in the quiescent gracilis muscle perfused at constant flow produced a significant (6%) decrease in resistance when arterial blood acetate was increased by a calculated 96 nmoles/ml. These studies suggest that acetate might be included among those metabolites that contribute to exercise hyperemia.U

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.

Antagonism of histamine edema formation by catecholamines.

Histamine (4 microgram base/min) infused into the brachial artery for 60 min greatly increases skin lymph flow and lymph protein concentration in forelimbs perfused either naturally or at constant inflow. In contrast, the simultaneous intrabrachial infusion of histamine and norepinephrine (4 microgram base/min of each) or histamine and isoproterenol (4 microgram base/min and 3 microgram/min, respectively) for 60 min failed to alter lymph protein concentration in forelimbs perfused either naturally or at constant inflow. The edema in forelimbs naturally perfused by histamine (4 microgram base/min) infused into the brachial artery for 60 min was also greatly reduced by the simultaneous histamine-catecholamine infusions. Phentolamine (in concentrations that antagonize the vascular actions of norepinephrine) failed to prevent the antagonism of histamine protein efflux by norepinephrine. Hence, it must be concluded that catecholamines antagonize the protein efflux by locally infused histamine, independent of alpha-adrenergic receptor activity.

Effects of systemically infused histamine on transvascular fluid and protein transfer.

Histamine (4-64 microgram base/min) infused into the brachial artery clearly promotes edema formation in forelimbs perfused at natural flow. In contrast, intravenously administered histamine, even in blood concentrations exceeding those achieved by local infusion, not only fails to promote edema formation, but rather causes net extravascular fluid reabsorption. In this study, high concentrations of histamine were infused into the left ventricular chamber to bypass the pulmonary circuit. Histamine (400-800 microgram base/min) infused into the left ventricle of the heart for 90 min produced marked hypotension and only very slight increases in forelimb skin lymph flow and lymph protein concentration and failed to produce visible signs of edema. Thus the differential actions of local and intravenous histamine on lymph flow, protein efflux, and fluid fluxes cannot be explained by uptake or destruction of histamine in the lung during intravenous infusions of this agent. It seems more likely that they result from different actions on microvascular pressure, surface area, and/or permeability to plasma proteins. Prior hypotension produced either by acetylcholine, systemically infused histamine, or arterial hemorrhage almost completely prevents the increase in skin lymph flow and lymph protein concentration by histamine infused locally into the brachial artery, even in forelimbs perfused at constant flow.

Effects of ischemia on forelimb weight and lymph protein concentration.

The aim of this study was to determine if edema develops in the canine forelimb after relief of prolonged ischemia. Two hours of ischemia was induced either by interrupting brachial artery inflow in collateral-free innervated, naturally and constantly perfused preparations or by applying a pressure cuff in intact preparations. Changes in extravascular fluid volume were inferred from changes in limb weight. Relief of ischemia produced a transient 1.7% increase in weight in the collateral-free, naturally perfused preparation but had no effect on weight in the collateral-free, constantly perfused or intact preparations. Skin lymph flow failed to change significantly and total lymph protein concentration increased only slightly. Thus, relief of 2 hr of ischemia does not produce marked edema or a large increase in microvascular permeability to plasma proteins in the dog forelimb.

Lymph flow and lymph protein concentration in the skin and muscle of the rabbit hind limb.

1. Three lymphatic beds have been found in the rabbit hind limb:(i) the lymph from the foot and ankle drains into lymphatics which run with the deep veins to the popliteal node;(ii) the superficial lymphatics of the medial skin from mid-calf to the groin enter the inguinal node while those of the lateral skin drain into the popliteal node;(iii) the lymph draining the muscles collects in vessels which do not enter the popliteal node but join the femoral lymphatic post-nodally.2. The lymphatic system of the hind limb is regionalized so that lymph from a specific area enters the popliteal node in one specific lobe and no other.3. By cannulating the femoral lymphatic and ligating the post-nodal lymph vessel close to the point at which it leaves the node it was possible to collect pure muscle lymph.4. The mean muscle lymph flow was 21 mul./100 g.min whilst the skin lymph flow was 240 mul./100 g.min. The mean protein concentration of muscle lymph was usually somewhat higher than that of skin lymph.5. After nerve stimulation there was an increase in muscle lymph flow but no increase in protein concentration.6. After a mild thermal injury there was no change in muscle lymph flow or its protein concentration, but there was an enormous increase in the leakage of lactic dehydrogenase indicating considerable cellular injury. On the other hand a significant increase in both protein concentration and flow of skin lymph occurred after thermal injury.

CONDITIONS IN THE SKIN INFLUENCING INTERSTITIAL FLUID MOVEMENT, LYMPH FORMATION, AND LYMPH FLOW

CONDITIONS IN THE SKIN INFLUENCING INTERSTITIAL FLUID MOVEMENT, LYMPH FORMATION, AND LYMPH FLOW