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PubMed1990

A quantitative histochemical study of the microvasculature of irradiated skin.

Short-term X-ray damage to the microvasculature of the skin of newborn rats has been quantitated using Horseradish Peroxidase as a tracer. Image analysis of thick sections on which peroxidase was demonstrated histochemically revealed a radioinduced increase in vascular volume coupled with a decrease in vascular length and an altered frequency distribution of blood vessel calibers which resulted in early telangiectasia. The results afforded by direct counting of peroxidase positive macrophagic cells and microphotometric evaluation of peroxidase present in the connective tissue indicate a progressive increase in capillary permeability as a function of dose and time post-irradiation. The accuracy with which the affected region of blood vessels coincided with the area exposed to the beam favours the hypothesis of direct damage to the vessel wall as a major cause of radioinduced lesion.

Animals↗
PubMed1980

Microvascular exchange. Kinetic analysis of plasma disappearance curves.

The present paper presents a survey of the kinetic "black box" analysis of plasma disappearance curves obtained after intravascular bolus injection of indicator molecules. Determinations of distribution volumes, capillary permeability, and clearance are based on calculations of mean transit times and mean sojourn times for the system constituents from the entire plasma disappearance curve. The widely used compartmental analysis is criticized, and it is emphasized that more or less arbitrarily chosen "half-life" times are not expressions of meaningful physiological and pharmacological processes.

Capillary Permeability↗
PubMed1996

Microinjection technique for pharmacological evaluation of microvascular permeability in human skin.

A new technique which combines skin microinjection of minute amounts of drugs (0.5 microliter) and measurement of capillary permeability by intravital fluorescence videomicroscopy and densitometry is introduced. Glass micropipettes with a tip diameter of 7-9 microns are inserted by a micromanipulator into the stratum papillare containing the capillary loops and used for microinjection by microsyringe and special dispenser. Transcapillary diffusion of sodium fluorescein applied by intravenous bolus injection is visualised by fluorescence videomicroscopy and stored on videotape. Perivascular fluorescent light intensity (FLI) is measured in arbitrary units (AU) by videodensitometry around the site of microinjection during playback of the videotapes. The method was tested by microinjection of 0.5 microliter histamine (1% solution) at the distal tibial plateau. Mean FLI values representing microvascular permeability were 2186 AU 10 min after microinjection of histamine, 420 AU after physiologic saline and 1228 AU after histamine combined with oral intake of 20 mg cetirizine. Cetirizine significantly reduced (P < 0.01) the increased permeability induced by histamine. However, the mean values after injection of the H1-blocker were still significantly enhanced (P < 0.01) when compared to the mean values observed after injection of physiologic saline solution, which provoked only minor microtrauma. The technique offers new scope for pharmacological testing in man.

Adult↗
PubMed2000

Choroidal vascular permeability in visually regulated eye growth.

The choroidal thickness fluctuates both diurnally and in response to changes in visual input. The fluctuations may represent a physiologic means of aligning the retinal photoreceptors with the focal position of distant images during the emmetropization process. To evaluate the basis for choroidal thickness changes, we studied the sources of the extravascular fluid in the chick choroid in two visually-regulated ocular growth conditions: accelerated ocular growth in goggle-induced form-deprivation myopia and ocular growth retardation in the recovery from myopia after goggle removal. Two week old chicks, controls, myopic and those recovering from myopia, received fluorescein dextran (MW = 140,000) as a tracer. It was given by intravenous injection to identify a potential vascular pathway and by intracameral injection to identify a potential pathway from the anterior chamber to the suprachoroidal space. Using a microscopically positioned needle, clear fluid was aspirated from the suprachoroidal space of the enucleated chick eye; this fluid presumably corresponds to the contents of the lacunae, prominent lymphatic-like structures of the chick choroid. Plasma, aqueous humor and suprachoroidal fluid were sampled 1 hr after injection and assayed for both protein content and the tracer dye. Sulfated glycosaminoglycans were assayed in the suprachoroidal fluid, choroid and sclera under each experimental condition. In control chicks, aqueous humor and suprachoroidal fluid protein concentrations were about 0.8 and 9% of plasma levels respectively. Aqueous humor protein concentration was unaltered in myopic or recovering eyes. Suprachoroidal fluid protein concentration in myopic eyes fell dramatically to 1.5% of plasma levels (P < 0.001). In contrast, recovery from myopia led to a marked increase in suprachoroidal fluid protein level to 30% of that in plasma (P < 0.001). None of the procedures affected suprachoroidal fluid protein in the contralateral control eyes. In all three groups of chicks, fluorescein dextran distribution in the suprachoroidal fluid at 1 hr after intravenous injection tracked protein levels, with reduced levels in myopic eyes and elevated levels in recovering eyes. After intracameral injection, suprachoroidal fluid dextran levels were higher in injected eyes of control chicks (P < 0.01) and in recovering eyes (P < 0.001) but lower in myopic eyes (P < 0.01), compared to the levels in the respective contralateral non-injected eyes in each group. Sulfated glycosaminoglycan levels were at the limits of detection in the suprachoroidal fluid under all conditions and, on a whole choroid basis, were unaltered in the choroid in either myopia or recovery. Suprachoroidal fluid is lymph-like in nature and largely derives from plasma. Sulfated glycosaminoglycan levels do not seem to regulate the fluid content of the choroid in either myopia or recovery. Instead, the changes in protein and marker dye levels in myopic and recovering eyes suggest markedly altered choroidal circulatory dynamics and capillary permeability in both conditions.

Animals↗
PubMed2000

Comparison of blood-brain barrier permeability in mice and rats using in situ brain perfusion technique.

Here we present a method for measuring the permeability coefficient-surface area product (PS) values at the blood-brain barrier in mice, using the in situ brain perfusion technique originally developed for rats by Takasato et al. (Am J Physiol Heart Circ Physiol 247: H484-H493, 1984). Retrograde infusion into the right external carotid artery increased the carotid perfusion pressure in proportion to the perfusion rate. Intravascular volume and cerebral perfusion fluid flow at a perfusion rate of 1.0 ml/min in mice were similar to those in rats. In addition, the contribution of systemic blood to total flow in the hemisphere was small (only 3. 2%). These findings indicated that this perfusion rate is suitable for mice. The PS values of more than 20 different compounds were determined in mice by using the in situ brain perfusion technique, and comparisons were made with data from rats. There was a close relationship (1:1) between the PS values in mice and rats, indicating that brain capillary permeabilities are similar in mice and rats.

Animals↗
PubMed2002

Antiinflammatory activity of rotenoids from Clitoria fairchildiana.

Five structurally related rotenoids were isolated from the roots of Clitoria fairchildiana. The antiinflammatory activity was investigated using a capillary permeability assay. The protective effect was measured as the inhibition in vascular permeability produced by acetic acid in the peritoneal cavity. The results suggest that for maximum activity the maintenance of the B/C ring junction integrity is important. These findings support the traditional use of Clitoria species extracts in the treatment of inflammatory conditions.

Acetic Acid↗
PubMed1998

The pathogenesis of ovarian hyperstimulation syndrome: a continuing enigma.

PURPOSE: Our purpose was to review the available literature concerning the pathogenesis of ovarian hyperstimulation syndrome and, in light of the most recent information, to attempt to provide further insight on this iatrogenic complication associated with the induction of ovulation. METHODS: Published studies related to this topic were identified through a computerized bibliographic search. CONCLUSIONS: The exact mechanism for the development of ovarian hyperstimulation syndrome is still obscure. It is well established that the syndrome is associated with the process of ovulation induced by either luteinizing hormone or human chorionic gonadotropin. Following ovulation, one or more substances produced by the ovary are liberated in excess, increasing capillary permeability, resulting in the clinical features of the syndrome. It may well be that the syndrome is not triggered by a single mechanism but by the production and secretion of several substances acting in concert. These may include prostaglandins, cytokines, the ovarian reninangiotensin system, vascular endothelial growth factor, and nitric oxide.

Capillary Permeability↗
PubMed2006

Visualizing lung function with positron emission tomography.

Positron emission tomography (PET) provides three-dimensional images of the distributions of radionuclides that have been inhaled or injected into the lungs. By using radionuclides with short half-lives, the radiation exposure of the subject can be kept small. By following the evolution of the distributions of radionuclides in gases or compounds that participate in lung function, information about such diverse lung functions as regional ventilation, perfusion, shunt, gas fraction, capillary permeability, inflammation, and gene expression can be inferred. Thus PET has the potential to provide information about the links between cellular function and whole lung function in vivo. In this paper, recent advancements in PET methodology and techniques and information about lung function that have been obtained with these techniques are reviewed.

Animals↗
PubMed1984

Exaggerated inflammatory responsiveness plays a part in the pathogenesis of HLA-B27 linked diseases--hypothesis.

Ankylosing spondylitis, acute anterior uveitis and reactive arthritides, including enteroarthritis and uroarthritis , are all associated with the human leucocyte antigen (HLA) B27. The pathogenesis of these diseases is not known, but it may involve inflammatory responsiveness of the host. In an acute inflammatory reaction, neutrophils are considered to cause tissue injury by both liberating lysosomal enzymes and generating toxic oxygen-derived free radicals. Furthermore, they may regulate both capillary permeability and the rate of vasodilatation at the site of inflammation. Evidence has accumulated that neutrophil responses to a phlogistic stimulus are enhanced in HLA-27 positive subjects. We suggest that hyperreactive neutrophils trigger a vicious circle of inflammation and render the subjects susceptible to exaggerated tissue injury.

Arthritis↗
PubMedDate not supplied

[Comparative evaluation of the role of protein in the diet therapy of ischemic heart disease and rheumatism with a slight degree of activity].

The patients with chronic heart disease (265 subjects) and with little active rheumatic fever (145 subjects) received two variants of isocaloric diets which differed only in protein quota. The former diet contained the physiological norm of protein (100 g) and the latter one a higher quota (130 g). As a result of the treatment the subjective sensations and objective status of all the patients improved. Evaluation of the time course of lipid metabolism, the system of hemostasis, capillary permeability and immunological reactivity showed that the diet containing the physiological norm of protein appeared the most effective in patients with ischemic heart disease, whereas that with a higher protein quota turned out the most adequate in patients with rheumatic fever.

Adult↗
PubMed1979

Idiopathic edema as a cause of nonarticular rheumatism.

Six women, aged 24 to 53, presented with symptoms of diffuse aching, morning stiffness, and fatigue, but demonstrated no objective abnormalities on joint examination or in laboratory studies. Each was found to have idiopathic edema, a disorder of fluid retention probably related to an abnormality of capillary permeability in which transudation of fluid into the subcutaneous tissues of dependent parts may result in swelling and discomfort. The rheumatic symptoms improved when therapeutic measures were directed against the accumulation of edema fluid. This syndrome may account for a minority of cases of nonarticular rheumatism in women.

Adult↗
PubMed1985

The hCG-induced increase in hormone uptake and interstitial fluid volume in the rat testis is not mediated by steroids, prostaglandins or protein synthesis.

The possible mediation by steroids, prostaglandins or protein synthesis on the hCG-induced increase in hormone uptake and interstial fluid volume in the rat testis in vivo was studied following a single iv injection of hCG. A high dose of hCG increased its own uptake in the testis and this uptake coincided with an increase in capillary permeability and accumulation of interstial fluid. The possible role of steroids, prostaglandins and protein synthesis in these changes was studied in vivo using aminoglutethimide, indomethacin and cycloheximide, respectively, as inhibitors. However, none of these prevented the hCG-induced changes in uptake and interstial fluid volume, which suggests that they do not mediate this phenomenon.

Animals↗
PubMed1992

High-dose vitamin C therapy for extensive deep dermal burns.

We studied the haemodynamic effects of antioxidant therapy with high-dose vitamin C administration (170 mg/kg/24 h) in guinea-pigs with 70 per cent body surface area deep dermal burns. The animals were divided into three groups of six animals each. Group 1 was resuscitated with Ringer's lactate solution according to the Parkland formula; group 2 with 25 per cent of the Parkland formula with vitamin C; and group 3 with 25 per cent of the Parkland formula without vitamin C. There were no significant differences in heart rates or in blood pressures between the groups throughout the 24-h study period. Group 3 showed significantly higher haematocrit values at 3 h postburn and thereafter as compared with those of group 2. The cardiac output values of group 2 were significantly higher than those of group 3, but equivalent to those of group 1. The water content of the burned skin in group 2 was significantly lower than that in the other groups, indicating that increased postburn capillary permeability was minimized by the administration of vitamin C. With adjuvant high-dose vitamin C administration, we were able to reduce the 24-h resuscitation fluid volume from 4 ml/kg/per cent burn to 1 ml/kg/per cent burn, while maintaining adequate cardiac output.

Animals↗
PubMed1975

[Blood, urine and bile levels of ampicillin during continuous intravenous infusion].

During and after continuous i.v. infusion of 0.25 g ampicillin (Binotal-R) per hour, serum and urine concentrations were determined in 6 healthy adults (volunteers) and in 12 geriatric patients with normal liver and kidney function. In old persons serum levels were higher and after the end of infusion decreased more slowly than in young adults. These data may be explained by a lower capillary permeability and renal clearance in older people. In patients with T-tube drainage after cholecystectomy, bile levels of ampicillin (during i.v. continuous infusion of 0.25 g/h) were equal to double those in serum. Recovery from the file was calculated as 0.1-0.2 percent.

Adult↗
PubMed1983

Regional measurements of blood-to-tissue transport in experimental RG-2 rat gliomas.

Regional measurements of blood-to-tissue transport were performed in transplanted RG-2 rat gliomas using [alpha- 14C]aminoisobutyric acid (AIB), quantitative autoradiography, and equations to express a unidirectional transfer constant. Thirty-eight intracranial tumors in ten rats were analyzed according to location; 23 intraparenchymal tumors, eight meningeal tumors, six fourth-ventricular tumors, and one third-ventricular tumor were studied. Except for the small third-ventricular tumor, the transfer constant (K) for AIB was similar in all groups and ranged from 0.031 to 0.038 ml/g/min. Within individual tumors, regional variation of K was also small, although some local variation could be correlated with histological features. The K for AIB decreased in brain around tumor and, at a distance of 300 microns from tumor edge, had returned to values similar to those of normal cortex (0.002 ml/g/min). An average extraction fraction (E) of 0.09 was calculated for AIB in the RG-2 tumors. The low E suggests that delivery of water-soluble chemotherapeutic drugs to RG-2 tumors should be limited more by capillary permeability or surface area than by blood flow. RG-2 is an ideal experimental tumor with which to test drug delivery and the methods that attempt to increase drug delivery in brain tumors.

Aminoisobutyric Acids↗
PubMed2001

An experimental rat model for studying pulmonary microcirculation by in vivo videomicroscopy.

It is unclear what role pulmonary microcirculatory disorders play in the pathogenesis of adult respiratory distress syndrome. The aim of this study was to establish a rat model for the direct visualization of pulmonary microcirculation by in vivo fluorescence videomicroscopy. The pulmonary terminal vascular bed was visualized and the microcirculatory parameters of leukocyte sticking, erythrocyte velocity, capillary permeability, and interalveolar septal diameter were quantified. These parameters were examined simultaneously. The preparation was stable for 120 min. Under hyperthermia, there was increased permeability with a relative fluorescence of 0.39 +/- 0.19 compared to 0.16 +/- 0.13 in the control group, and interalveolar septal diameters were wider (30.7 +/- 2.9 microm) than in control animals (17.3 +/- 3 microm). Under hypothermia and hypovolemia, the erythrocyte velocity was lower (0.351 +/- 0.063 and 0.378 +/- 0.044 mm/s) than in control groups (0.527 +/- 0.07 mm/s). Under hypoventilation, we observed a higher amount of leukocyte sticking (3.1 +/- 1.1 vs 1.8 +/- 0.8 cells/alveolus) and increased permeability (relative fluorescence 1.03 +/- 0.37 vs 0.16 +/- 0.13 in the control group). The model of rat lung exposure for direct examination of microvascular structures in living animals was valuable because it remained stable for 2 h under baseline conditions and demonstrated distinct changes in microcirculatory parameters following specific pathophysiological interventions.

Animals↗
PubMed1984

The effects of phentolamine and isoproterenol in experimental hemorrhagic shock in the dog.

The effects of phentolamine and isoproterenol were investigated in eight dogs versus eight control dogs. The dogs were placed into simulated hemorrhagic shock using a reservoir to maintain arterial pressure at 40 mmHg until the level of the reservoir decreased to 20% of the maximum shed volume, or for 2 hr in the isoproterenol groups. After 30 min, during which phentolamine, isoproterenol, or saline was infused, the remaining blood was reinfused. Phentolamine was given as a 5-mg intravenous bolus. Isoproterenol was infused at 2.0 micrograms/kg/min. The dogs were monitored until their arterial pressure declined to 70 mmHg (50 mm for isoproterenol) or death ensued. Phentolamine lowered peripheral resistance and the size of the vascular space increased as shown by the rapid uptake of blood, 214.0 +/- 12.5 ml, during the 30 min after injection. The control group took back only 72.5 +/- 7.5 ml. Although reinfusion of the shed blood restored blood pressure to near normal for a short period, all groups showed a progressive decline in arterial pressure. There was no evidence that phentolamine or isoproterenol significantly decreased capillary permeability or that renal or pulmonary function were significantly altered by treatment. A large increase in venous oxygen content occurred following phentolamine, and a mild inotropic and vasodilator action lasted for about 30 min. Isoproterenol also decreased postinfusion arterial pressure. Neither drug influenced the hypoglycemia seen after reinfusion.

Animals↗
PubMed2001

Pathogenesis of malignant ascites: Starling's law of capillary hemodynamics revisited.

Peritonitis carcinomatosa, indicating the presence of malignant cells in the peritoneal cavity, is a well-known complication of malignant disease. As a result, so-called malignant ascites develops. Malignant ascites is a debilitating condition for which no effective anti-tumor therapy is available. Frequent draining may be necessary to relieve pain and discomfort. Most studies regarding malignant ascites focus on diagnosis and treatment. In this paper. we will address the subject from a pathophysiologic perspective, using the characteristics of malignant ascites, Starling's equation of capillary forces, and recent knowledge regarding biologically active peptides produced by tumor cells. Following this approach. apart from decreased lymphatic ascites absorption, increased net capillary fluid-production can be identified as a contributing feature of ascites formation. The increased net filtration is due to an increase of overall capillary membrane-surface, increased capillary permeability and a subsequent increase of intraperitoneal protein concentration leading to increased intraperitoneal oncotic pressure. This sequence might be the result of biologically active peptides produced by tumor cells such as vascular endothelial growth factor and basic fibroblast growth factor. Interference with these mediators may serve as a target in future therapeutic strategies.

Ascites↗