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PubMed1990

Tumor accumulation mechanism of 99mTc-DL-homocysteine, a model compound for the development of tumor-imaging radiopharmaceuticals.

To elucidate the tumor accumulation mechanism of 99mTc-DL-homocysteine (99mTc-Hcy), the role of mercaptalbumin, a carrier protein of 99mTc-Hcy in blood, was studied. 99mTc-Hcy bound to serum mercaptalbumin was carried to tumor tissue, efficiently adsorbed onto the cell surface, released from albumin, and taken up by the cells. An enlarged capillary permeability observed in tumor tissue played an important role in the transport process.

Animals↗
PubMed1984

Rapid transcapillary exchange and unidirectional neuronal uptake of noradrenaline in the perfused rabbit heart.

Capillary permeability and cellular uptake of noradrenaline by the isolated artificially perfused rabbit heart was measured using rapid (less than 30 s) single-circulation tracer-dilution techniques. In a single coronary circulation capillary extractions of L-[14C]noradrenaline and D-[3H]mannitol (extracellular reference) relative to an intravascular marker, 125I-labelled albumin, were similar and above 60%. The 'apparent' volume of distribution for tracer noradrenaline was 2.5-fold larger than that measured for D-mannitol (0.32 ml g-1) suggesting cellular uptake of the amine. Unidirectional noradrenaline uptake was estimated by directly comparing coronary sinus dilution profiles of L-[3H]noradrenaline and D-[14C]mannitol. Michaelis-Menten saturation kinetics based on a single-entry system were determined (Km = 2.8 +/- 1.5 microM, Vmax = 2.1 +/- 0.5 nmol min-1 g-1, n = 4) by perfusing hearts with varying concentrations of L-noradrenaline (1-10 microM). Various known inhibitors of noradrenaline uptake were investigated to determine whether uptake was mediated by neuronal (uptake1) and/or extraneuronal (uptake2) mechanisms. Desipramine (5 microM), imipramine (5 microM) and metaraminol (2 microM) resulted in a 66-94% inhibition of noradrenaline influx. In comparison, the steroids, 17 beta-oestradiol (1 microM) and corticosterone (10 microM), and the noradrenaline metabolite normetanephrine (5 microM) caused virtually no inhibitory effects. The beta-adrenergic antagonist propranolol (5 microM) was also relatively ineffective. These results together with the kinetic constants estimated suggest that the rapid noradrenaline uptake reflects transport into adrenergic neurones lying in the coronary interstitium. The high resolution of this paired-tracer dilution technique has permitted a 'non-invasive' study of neuronal uptake mechanisms and its application may be of clinical value.

Animals↗
PubMed1978

Effects of solute-coupled transport on lymph flow and oncotic pressures in cat ileum.

The effects of net volume absorption rate on steady-state lymphatic and capillary volume flows, lymphatic protein flux, and lymph oncotic pressure were analyzed in an isolated vascularly perfused cat ileum preparation. Solute-coupled fluid transport was stimulated by instilling either Tyrode solution, Tyrode + glucose, Tyrode + taurocholic acid (TC), Tyrode + TC + oleic acid, or Tyrode + aspartic acid, into the ileal lumen. Lymph flow increased in a sigmoidal fashion as net volume absorption rate increased. A linear relationship was observed between lymphatic protein flux and net volume absorption rate. The relative contributions of the intestinal capillary and lymphatic systems in removing absorbed volume from the mucosal interstitium was highly dependent on the rate of net volume absorption. Lymph oncotic pressure decreased progressively as net volume absorption rate increased with a maximal reduction in lymph oncotic pressure of 6.0-7.0 mmHg at the higher volume absorption rates. The results of this study indicate that 1) the rate of solute-coupled fluid transport greatly influences the rate of intestinal lympathic and capillary volume flows, lymphatic protein flux, and lymph oncotic pressure, 2) a reduction in tissue oncotic pressure may serve as the major driving force for vascular removal of absorved volume, and 3) the increase in capillary permeability to plasma proteins during fluid transport is related to the rate of volume absorption.

Animals↗
PubMed1985

Protein-losing enteropathy in systemic lupus erythematosus.

A 33-year-old woman presented a recurrent steroid-sensitive protein-losing enteropathy as the major manifestation of systemic lupus erythematosus. An increased capillary permeability for proteins is considered to be the most likely explanation.

Adult↗
PubMed1994

Evans blue permeation of intestinal mucosa in the rat.

The azo dye Evans blue (EB; molecular weight, 960.83) is widely used as an indicator of increased capillary permeability. In the present study, however, rat gut absorption of EB was investigated after dye instillation in either the small or large intestine. During a brief period of ether anaesthesia, EB was injected either into jejunal loops with a challenge period of 30 or 60 min or into a proximal and a distal colon loop with a challenge period of 30, 60, or 120 min. After the rats had been killed the intestinal specimens were washed with 6 mM acetylcysteine dissolved in phosphate-buffered saline, which efficiently cleared the tissues of mucus, and thus of EB trapped in mucus. Only EB absorbed by the gut wall remained to be estimated, and this absorption was found to be both dose- and time-dependent in the jejunum and the colon. After instillation in the colon, but not in jejunum, EB could be detected in the blood. EB absorption from the jejunum remained unaffected by the addition of either ouabain (1 mM) or lidocaine (0.38 mM). Either of these compounds inhibited EB uptake in the proximal part of the colon, while enhancing it in the distal part. Fluorescence microscopy showed penetration into the intestinal wall to be a prerequisite for EB to become fluorescent, and EB fluorescence increased with time. It is proposed that EB is transported over the mucosa by the paracellular route and that the amount of absorbed EB reflects epithelial permeability differently in different parts of the gastrointestinal tract.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Freeze-fracture replica study of capillary endothelium after embolization in the dog.

The underlying mechanisms that lead to brain edema following ischemic insult have been subject to much debate. In this study, experimental cerebral infarction was produced in 25 dogs by injecting 1 or 2 silicone rubber cylinders through the cervical internal carotid artery. The animals were sacrificed 24 hours after embolization. Freeze-fracture studies were conducted on the plasma membrane of the capillary endothelium from 15 control and 25 ischemic dogs. No definite findings of tight junction opening were made in the ischemic preparations. Pinocytotic vesicles were seen as concave areas on the protoplasmic face (PF) of the plasma membrane and as protrusions on the extracellular face (EF). The average pinocytotic vesicle count per square micron was increased in ischemic animals. On the luminal side, it reached 22.0 +/- 1.2/sq mu in the 50 PF samples and 29.5 +/- 1.3/sq mu in the 50 EF samples in the experimental preparations, as compared to 7.2 +/- 0.5 sq mu in the 50 PF samples and 9.0 +/- 0.6 sq mu in the 50 EF samples in normal cortex. The average area of the vesicles was also enlarged in experimental animals: 4990.7 +/- 798 sq nm in the 50 PF samples and 4762.8 +/- 878 sq nm in the 50 EF samples, as compared to 3567.7 +/- 570 sq nm in the 50 PF samples and 3404.5 +/- 573 sq nm in the 50 EF samples in normal cortex (p greater than 0.01). These results indicate that transcellular transportation by pinocytotic vesicles plays an important role in the increase of capillary permeability observed in an ischemic model.

Animals↗
PubMed2006

T cell activation alters intestinal structure and function.

Treatment with anti-CD3 antibody (anti-CD3) causes transient diarrhea. In this issue of the JCI, Clayburgh et al. show that, in jejunum of mice injected with anti-CD3 or with TNF, fluid accumulation and changes in epithelial phenotype develop, the latter including an increase in the passive permeability to proteins, smaller solutes, and water and the endocytosis of the brush border Na+/H+ exchanger, thereby inhibiting Na+ absorption (a second cytokine, LIGHT, has the former effect, but not the latter) (see the related article beginning on page 2682). These phenotypic changes, by themselves, do not, however, explain increased fluid secretion. Since active anion secretion is not stimulated (in fact it is inhibited), a non-epithelial cell-mediated driving force must be present--most likely an increase in interstitial pressure due to an effect of TNF on capillary permeability, smooth muscle contractility, or both.

Animals↗
PubMed1977

Variation in output of leukocytes and erythrocytes in human peripheral lymph during rest and activity.

The output of lymphocytes, monocytes, granulocytes and erythrocytes in peripheral leg lymph from healthy volunteers has been followed during night and everyday activity, during and after venous stasis, ergometer cycling and warm foot bath and during immobilisation in horizontal position over two 24-hour periods. The output of lymphocytes exceeded the output of monocytes and erythrocytes. Granulocytes were not found except immediately after cannulation. The cell output was low during night rest and the horizontal position for 24 hours. After assumption of the upright position the output of lymphocytes increased about 80 times and the output of erythrocytes 40 times probably because of washout of cells accumulated in tissue during rest. During ergometer cycling and venous stasis the output of cells increased and even more in the one hour rest period following this experiment. During venous stasis the output dropped but increased after the stasis had been released. The pattern of variation in lymphocyte, erythrocyte and monocyte output was the same. This indicate that the fluctuation in output depends on variation in blood flow in the tissue. The output of cells during and after heating seems to be dependent also on increased capillary permeability for cells as the output of erythrocytes exceeded the output of lymphocytes. The high erythrocyte/lymphocyte ratio in blood versus a low ratio in lymph shows that these two cell types pass through the capillary wall by different mechanisms.

Adult↗
PubMed1994

A new model for the study of pulmonary microcirculation: determination of pulmonary edema in rats.

Traditional studies of the lung microcirculation and pulmonary edema commonly employ indirect measurements of vascular hemodynamics or the examination of isolated lung segments. We have developed a new model which allows the direct investigation of the microcirculation at the surface of the lung in rats. A pulmonary window chamber of novel design was implanted into the chest wall of Sprague-Dawley rats to allow both short- and long-term observation of the pulmonary microvasculature in living animals. Pulmonary edema was induced by i.v. injection of either oleic acid or compound 48/80. The progression of pulmonary edema and alveolar flooding was assessed by monitoring the leakage of fluorescein-labeled albumin and rhodamine dye from the pulmonary capillaries into the alveoli. Animals given oleic acid or compound 48/80 showed progressive leakage of both fluorescein-labeled albumin and rhodamine. The greatest leakage occurred over the first 30 min of observation. No changes in pulmonary capillary permeability were observed in control animals over the period of observation.

Animals↗
PubMed1992

Contrast-enhanced fat saturation magnetic resonance imaging for studying the pathophysiology of osteonecrosis of the hips.

We imaged 75 hips in 40 patients using fat saturation technique before and after intravenous injection of contrast (0.1 mmol/kg gadolinium diethylene triamine penta-acetic acid, Gd-DTPA). Eighteen hips in 11 patients were determined to be osteonecrotic, either by pathologic or clinical examination. In the osteonecrotic hips, three distinct patterns of enhancement were found: (I) focal area outlined by brightly enhancing rim (7 hips); (II) diffuse enhancement in the femoral head and neck extending into the femoral shaft (3 hips); and (III) a combination of patterns I and II (8 hips). Our data support the hypothesis that early nontraumatic osteonecrosis is associated with hyperemia and/or an increase in capillary permeability rather than acute devascularization, and that diffuse marrow edema is the initial finding in early nontraumatic osteonecrosis.

Capillary Permeability↗
PubMed1978

An "on-line" colorimetric method for repeated, rapid determinations of capillary diffusion capacity.

The single injection indicator diffusion method for estimation of capillary diffusion capacity (Crone 1963) has been developed to provide directly visualized, continuous colorimetric recordings of the venous time-concentration curves by means of a two-colour densitometer system. Cardio-Green, bound to albumin, is used as the non-permeant ("reference") tracer and Cr-EDTA as the permeant one. The artificially perfused hindquarter muscle vascular bed of rats is used. Highly reproducible curve recordings can be obtained every fourth minute. Accidental disturbances of the recordings are readily detected. Thus, compared to the fractional venous sampling technique, the present technique has the great advantage of allowing immediately controlled and frequently repeated determinations of capillary diffusion capacity. It is therefore easily used together with measurements of filtration-absorption events, e.g. for frequent quantitative comparisons of capillary diffusion and filtration capacities over a wide range of induced changes in perfused capillary surface area and/or capillary permeability. The main limitation is that the employed permeant tracer necessitates the use of erythrocyte-free perfusates.

Animals↗
PubMed1990

Alterations in plasma volume and protein during cycle exercise throughout pregnancy.

The purpose of this investigation was to determine the effects of cycle exercise on maternal plasma volume (PV) and protein dynamics during pregnancy. Sixteen healthy gravidas (age = 23 +/- 4.6 yr) cycled for 5 min (75 W) at 4 wk intervals throughout term. Venous blood samples were drawn immediately prior to and during the last minute of exercise. Relative (percent) PV changes during exercise were calculated from hematocrit ratios and hemoglobin concentrations. Plasma was analyzed for total protein ([TP]) and albumin ([ALB]) concentrations and colloid osmotic pressure (COP). Resting blood volumes were also estimated (carbon monoxide rebreathing) so that absolute PV (ml) and TP and ALB contents (g) could be determined. COP increases (P less than 0.001) during exercise were similar at all gestational ages. Plasma volume, TP, and ALB decreased during exercise with significantly (P less than 0.001) greater losses occurring from 29-32 wk gestation. This may indicate an increase in capillary permeability to large molecules when vascular volume was highest.

Adult↗
PubMed1970

The penetration of inulin, sucrose, mannitol and tritiated water from the interstitial space in muscle into the vascular system.

1. An isolated gastrocnemius muscle from cat was perfused with a modified Ringer fluid containing the extracellular tracers mannitol, sucrose and inulin and in some cases tritiated water (HTO). When equilibration of the tracers between the perfusate and the tissue was obtained, perfusion with tracer-free fluid was started.2. The fractional rate of escape, Phi (t), of the tracers was followed. For all tracers it declined steadily with time. The rate of decline was faster for the smaller extracellular molecules when any combination of two extracellular tracers was studied.3. Arrest of flow for 1-2 min lead to an increase in Phi (t) for the extracellular tracers when flow was resumed. There was little or no effect upon Phi (t) for HTO.4. Doubling the rate of flow had no effect upon Phi (t) for the extracellular tracers, while that of HTO increased.5. We conclude that the cause of the decline in Phi (t) for the extracellular tracers is concentration gradients in the interstitial space. The findings raise problems in methods for studying capillary permeability by means of the fractional rate of escape of tracers from the interstitial space into the vascular system.

Animals↗
PubMedDate not supplied

Morphological study of blood-labyrinth barrier in the vestibular organs under normal and experimental acute hypertensive and acute hypotensive conditions.

In order to examine a blood-labyrinth barrier in the vestibular region, capillary permeability of the vestibular organs, i.e. the sacculus, the utriculus and the ampullae of semicircular canals, were studied light and electron microscopically by the horseradish peroxidase (HRP) tracer method. Intravenously infused HRP was not observed outside capillaries because of the tightness of endothelial tight junctions and the paucity of pinocytotic vesicles. Furthermore, the effect of drug-induced acute hypertension and acute hypotension on the capillaries of the vestibular organs was studied morphologically using the tracer technique. In each experiment, there was no extravasation of HRP from capillaries, thus agreeing with the results of the experiment made under normal conditions. These findings mean that capillaries of the vestibular region are of ordinary brain capillary type and contribute to the blood-labyrinth barrier to macromolecules such as HRP both under normal conditions and following abrupt changes in blood pressure.

Animals↗
PubMedDate not supplied

[Ultrastructural observations on experimental shock lung].

Intercellular junctions in the alveolar epithelium and in the capillary endothelium in the dogs after hemorrhagic shock (mean BP 40 mm Hg for 3 hours) and from control dogs were observed in the electron microscope using the freeze-fracture and etch technique. Following shock, tight junctions (zonulae occludentes) in the alveolar epithelium which were well developed with may strands in control animals showed alterations in substructure. Some desintegration and disappearance of junctional strands in "focal" regions were occasionally observed in the endothelium as well. The increased pulmonary capillary permeability observed physiologically after hemorrhagic shock may be explained by such alterations of endothelial zonulae occludentes.

Animals↗
PubMed1984

Effects of experimental cirrhosis on splanchnic microvascular fluid and solute exchange in the rat.

In human cirrhosis, there is evidence that there are considerable alterations in fluid and solute exchange in the hepatic and intestinal microcirculations . Experimental cirrhosis was induced in rats by using oral phenobarbitone and carbon tetrachloride inhalation over an 8-wk period. Portal venous pressure, hepatic and intestinal lymph flows, and lymph and plasma protein concentrations were measured. Liver samples were obtained for histologic examination. Portal venous pressure increased from a normal value (control animals) of 9.0 (6.3-13.1) cmH2O to 17.9 (9.0-29.0) cmH2O in cirrhotic rats. There was a strong correlation between the degree of fibrotic change on histology and portal venous pressure. Lymph flows from the intestine and liver in cirrhotic animals were increased threefold and 30-fold, respectively, over values obtained from control animals. There was a good correlation between intestinal and liver lymph flows and portal venous pressure. Analysis of lymph/plasma protein concentration ratios at various lymph flow suggests that capillary permeability in the small intestine during sustained portal hypertension is comparable to that in normal animals. However, the highly permeable blood-lymph barrier of the normal liver becomes markedly restrictive in cirrhotic animals.

Animals↗
PubMed1982

The effect of sustained venous hypertension on the skin capillaries of the canine hind limb.

An increased number of skin capillaries has been found in human skin subjected to sustained venous hypertension. To investigate this observation, venous hypertension was produced in the hind limb of Greyhounds by fashioning an arteriovenous (AV) fistula between the femoral vessels. This caused an increase in the number of capillaries in the skin of the lower leg. The capillary permeability of normal legs and legs subjected to chronic venous hypertension was then studied by observing the movement of radioactive molecules from the plasma to the fluid within Guyton capsules. Fibrinogen, a large molecule, leaked out of the capillaries significantly faster in the limbs with a high venous pressure and an enlarged capillary bed. It is suggested that the increase in the size and permeability of the dermal skin capillaries secondary to prolonged venous hypertension is the cause of lipodermatosclerosis and venous ulceration.

Animals↗