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PubMed1975

The effect of Ca++, Mg++ and H+ on the capillary permeability of the rete mirabile of the eel, Anguilla vulgaris L.

The effects of EDTA, and of varying pH on the capillary permeability in the rete mirabile have been investigated: EDTA had to be added to the perfusate in excess to the total content of Ca++ and Mg++ in plasma in order to elicit changes in the permeability. When exposed to sufficient amounts of EDTA, the capillary permeability to hydrophilic molecules increased several fold whereas the permeability to THO and lipid-soluble molecules remained unchanged. The increase in the permeability to high-molecular dextrans was delayed. When the EDTA-effect was maximal the mutual relationship between the permeabilities of THO and the lipid-insoluble molecules became close to the ratio between the corresponding free diffusion coefficients in water. During exposure to EDTA the content of K+ and Na+ of the rete tissue (mostly endothelial cells) became very similar to that of plasma. Similar effects were obtained when the rete was perfused with plasma having a pH below 4 or above 9. The EDTA-effect was reversible during its initial stage. Perfusions with plasma in which Ca and Mg had been removed by dialysis at pH 3.5 were performed. When an EDTA-effect had been induced with this type of perfusates, it could be reversed by addition of equimolar amounts of either Ca++ or Mg++. This indicates Ca++ and Mg++ to be equally important in order to assure normal permeability properties of the capillary membrane.

Anguilla↗
PubMed1991

Increased capillary permeability in rat brain induced by factors secreted by cultured C6 glioma cells: role in peritumoral brain edema.

To investigate whether brain tumors secrete a factor(s) responsible for peritumoral brain edema, we studied the effect of conditioned medium from cultured C6 glioma cells on rat brain capillary permeability. Three different fractions of conditioned medium were obtained. SUP-N was a culture supernatant incubated 4 hours in serum-free medium. SUP-C was the 60-100 fold concentrated fraction obtained by dialysis-concentration of SUP-N; it contained 950 micrograms/ml of protein greater than 10 k-daltons from 3 x 10(8) cells. SUP-L was a water-dispersible lipid fraction from SUP-N; the major components of SUP-L were neutral lipids and free fatty acids. The supernatant fractions and their corresponding control solutions were infused into normal rat brain, and capillary permeability was determined using quantitative autoradiography by measuring the unidirectional entry constant, K (micrograms l/g.min), of 14C-alpha-aminoisobutyric acid (14C-AIB) into brain tissue. SUP-C and SUP-L significantly increased capillary permeability of normal brain; the effect of SUP-C was more intense and extensive than that of SUP-L. The highest mean K value (Kmax) of SUP-C was 10.83 +/- 0.99 and that of the control was 2.53 +/- 0.22 (p less than 0.001). The Kmax of SUP-L was 5.61 +/- 0.23 and that of the control was 2.67 +/- 0.36 (p less than 0.01). A time-course study after infusion of SUP-C demonstrated that more than 1.5 hours is required for the supernatant fraction to open the barrier and that the effect of SUP-C was reversible. The increase of capillary permeability induced by SUP-C was significantly inhibited by pretreatment of rats with dexamethasone (10 mg/kg, ip) 1 hour before intracerebral infusion of SUP-C (Kmax (untreated): 8.30 +/- 0.82, Kmax (treated): 1.33 +/- 0.64, p less than 0.001). These results indicate that experimental brain tumors secrete at least two different diffusible factors responsible for capillary endothelial leakage in normal brain. One is a protein of molecular weight greater than 10 k-daltons, whose effect is inhibited by glucocorticoids, and the other is a waterdispersible lipid.

Animals↗
PubMed1977

Capillary permeability to albumin in normotensive and spontaneously hypertensive rats.

Transcapillary passage of plasma proteins is enhanced in man's primary hypertension and it is debated whether this reflects increased permeability or merely a raised capillary pressure. To elucidate this problem, maximally vasodilated hindquarters of spontaneously hypertensive rats (SHR) and normotensive controls (NCR) were perfused in parallel at constant flow with dextran, horse serum or mixtures of the two, using labelled albumin as indicator of capillary permeability to macromolecules. By equal increases of venous pressure modest filtration was maintained during one hour, after which the edema and its albumin content were determined.--There was less edema in SHR, reflectin a slightly lower postcapillary resistance and a much higher precapillary resistance compared with NCR, which here resulted in a lower capillary pressure in SHR. In both SHR and NCR the presence of dextran slightly enhanced the capillary filtration coefficient but increased albumin permeability up to tenfold, also after antihistamine drugs. However, for each perfusate the SHR capillaries were, if anything, slightly less permeable to albumin than the NCR ones.--The results suggest that the enhanced transcapillary passage of plasma proteins in primary hypertension reflects an increased capillary pressure in some circuit(s), probably mainly skeletal muscle, resulting from the functional balance in vivo between the pre- and postcapillary resistances.

Animals↗
PubMed1986

Capillary permeability changes in the uteri of recipient rabbits after transfer of blastocysts from indomethacin-treated donors.

Blastocysts recovered from control or indomethacin-treated (10 mg/kg s.c. twice daily starting on Day 4.5 of pregnancy) donor rabbits were transferred to the uteri of Day-6 or 6.5 pseudopregnant recipients. The minimal time required to cause an increase in capillary permeability in the endometrium underlying control blastocysts was approximately 9 h. Blastocysts derived from the indomethacin-treated donors were depleted of PGE and PGF (determined by RIA) and were unable to produce any increase in capillary permeability during the same time period, although after 46 h in vivo the diameters of the implantation swellings related to control or indomethacin-treated blastocysts were not different. This suggests that, in the untreated recipients, blastocysts depleted of PGs can become replenished and then release these PGs in a site-directed manner. Indomethacin thus causes a delay rather than a complete inhibition of implantation. Incubation of the indomethacin-treated blastocysts in vitro led to replenishment with PGs, but such replenished blastocysts failed to induce an increase in capillary permeability within the same time-frame as control blastocysts. Evidence is presented that indomethacin is probably not the cyclooxygenase inhibitor of choice, since it interferes with PG uptake and efflux. Such an action could explain the failure of the replenished blastocysts to induce a normal increase in capillary permeability.

Animals↗
PubMedDate not supplied

[Radioisotopes for the evaluation of pulmonary capillary permeability in ARDS].

The dysfunction of pulmonary capillary represents the marker of Acute Respiratory Distress Syndrome (ARDS). Each current mean of investigation in ARDS (radiography, CT, ultrasonography, double dilution technique, electric impedance, bronchoscopy) has its downfalls and has not succeeded in becoming a gold standard in evaluation of this pathology. The development of any treatment is hampered by the lack of a rapid and objective method of evaluation of the progress of the disease. The radioisotopic evaluation of pulmonary capillary permeability realizes a picture of a physiologic process blood-interstitial exchange at pulmonary level. The most recent studies appear to suggest that this method of investigation can objectively evaluate and be a predictive parameter for ARDS evolution. We will present the principle of the radio-isotopic method and some of its current clinical applications.

Capillary Permeability↗
PubMed2000

Matrix metalloproteinases correlate with alveolar-capillary permeability alteration in lung ischemia-reperfusion injury.

BACKGROUND: Matrix metalloproteinases (MMPs) are able to degrade the endothelial basal lamina and increase vascular permeability. METHODS: In a porcine model of isolated-reperfused lung, we studied the alveolar-capillary permeability and the zymographic expression of MMP-9 and MMP-2 in the bronchoalveolar lavage fluid of lungs submitted ex vivo to ischemia in three preservation solutions [modified Euro-Collins (EC), low-potassium-dextran, modified-blood]. Twenty-two pigs were randomly divided into three groups according to the preservation solution used. One lung of each pig was rapidly reperfused and analyzed (control lung) although the other lung was reperfused and analyzed after 8 hr of ischemia (ischemic lung). RESULTS: Alveolar-capillary permeability, evaluated by the transferrin leak index, was increased after 8 hr of ischemia compared with controls in the three groups, but was significantly higher in the modified EC group. In the EC group, after 8 hr of ischemia, both proMMP-9 and MMP-9 increased significantly (8.8- and 22-fold, respectively) compared with controls and this increase correlated with the transferrin leak index. Neither proMMP-9 nor MMP-9 increased with the other two preservation solutions. The MMP-2 increase after ischemia was smaller and was also restricted to the EC group. CONCLUSION: MMP expression is enhanced during lung ischemia-reperfusion, especially in the presence of EC and this phenomenon correlates with the alteration of alveolar-capillary permeability.

Animals↗
PubMed1978

Effects of indomethacin on uterine capillary permeability and blastocyst development in rabbits.

Increased capillary permeability at implantation sites was demonstrated in rabbits by extravasation of intravascular blue dye on day 7 of pregnancy. Subcutaneous administration of indomethacin (Id, 8 mg/kg twice daily) on days 4-6 of pregnancy inhibited this uterine blueing response and appeared to reduce the size of implantation swellings. To test the latter observation blastocyst diameter and development of the embryonic disk were assessed at 144 hr post coitum. In females receiving indomethacin at the dose level which inhibited uterine blueing, blastocysts were significantly smaller than those from control females. Developmental staging of embryonic disks revealed only slight differences between the smaller (Id-treated) blastocysts and control blastocysts. No effect of Id was seen on ovarian function as judged by luteal weights and plasma progesterone and estradiol levels. Since the major biological effects of indomethacin are due to its inhibition of prostaglandin synthesis, it appears that prostaglandins may play a role in the uterine response to blastocyst stimulation and in the expansion of blastocysts in the rabbit.

Animals↗
PubMed2005

Inhibitory effects of sasanquasaponin on over-expression of ICAM-1 and on enhancement of capillary permeability induced by burns in rats.

The purpose of this study was to investigate the effects of sasanquasaponin (SQS) on ICAM-1 expression and capillary permeability induced by burns in rats. Male adult Sprague-Dawley (SD) rats were subjected to burns in the presence or absence of SQS, and then intravenously injected with Evans blue (60.0 mg/kg body weight). The levels of soluble ICAM-1 (sICAM-1) in sera were assayed using ELISA and the expression levels of transmembrane ICAM-1 (mICAM-1) in aorta were determined by Western blots and ICAM-1 mRNA levels were measured using semi-quantification RT-PCR. The capillary permeability was determined spectrophotometrically. The results showed that SQS markedly lowered the levels of sICAM-1 in sera, and considerably inhibited the over-expression as well as transcription of mICAM-1 in rat aorta. In addition, SQS dramatically inhibited the enhancement of dermal capillary permeability induced by burns in a dose-dependent manner. These results suggest that SQS, developed from Chinese traditional herbs, might be effective in decreasing inflammation induced by burns.

Animals↗
PubMed2002

Complete structure of an increasing capillary permeability protein (ICPP) purified from Vipera lebetina venom. ICPP is angiogenic via vascular endothelial growth factor receptor signalling.

The partial sequence of the increasing capillary permeability protein (ICPP) purified from Vipera lebetina venom revealed a strong homology to vascular endothelial growth factor (VEGF)-A. We now report its complete amino acid sequence determined by Edman degradation and its biological effects on mouse and human vascular endothelial cells. ICPP is a homodimeric protein linked by cysteine disulfide bonds of 25115 Da revealed by mass spectrometry. Each monomer is composed of 110 amino acids including eight cysteine residues and a pyroglutamic acid at the N-terminal extremity. ICPP shares 52% sequence identity with human VEGF but lacks the heparin binding domain and Asn glycosylation site. Besides its strong capillary permeability activity, ICPP was found to be a potent in vitro angiogenic factor when added to mouse embryonic stem cells or human umbilical vein endothelial cells. ICPP was found to be as potent as human VEGF165 in activating p42/p44 MAPK, in reinitiation of DNA synthesis in human umbilical vein endothelial cells, and in promoting in vitro angiogenesis of mouse embryonic stem cells. All these biological actions, including capillary permeability in mice, were fully inhibited by 1 microm of a new specific VEGF receptor tyrosine kinase inhibitor (ZM317450) from AstraZeneca that belongs to the anilinocinnoline family of compounds. Indeed, up to a 30 times higher concentration of inhibitor did not affect platelet-derived growth factor, epidermal growth factor, FGF-2, insulin, alpha-thrombin, or fetal calf serum-induced p42/p44 MAPK and reinitiation of DNA synthesis. Therefore, we conclude that this venom-derived ICPP exerts its biological action (permeability and angiogenesis) through activation of VEGF receptor signaling (VEGF-R2 and possibly VEGF-R1).

Amino Acid Sequence↗
PubMed1984

Steroid effect on capillary permeability in gram-negative septic shock. Evaluation by vitreous fluorophotometry.

The purpose of this study was to use vitreous fluorophotometry to evaluate the effects of glucocorticoids on capillary permeability during gram-negative septic shock. Twelve preconditioned mongrel dogs were cannulated with arterial lines and Swan-Ganz catheters for complete hemodynamic monitoring. All 12 dogs were injected with fluorescein and live Escherichia coli intravenously. Six of the 12 dogs were administered methylprednisolone at set intervals after the initiation of the E coli infusion. Vitreous fluorophotometric recordings were taken hourly. Leakage of fluorescein into the extravascular space occurred in both groups, up to several hours after E coli infusion. However, in the steroid group, the capillary permeability decreased and stabilized following the initial increase in permeability. We conclude that steroids, when administered during the development of gram-negative septic shock, may modify capillary permeability changes.

Animals↗
PubMed2005

Noninvasive evaluation of acute capillary permeability changes during high-volume ventilation in rats with and without hypercapnic acidosis.

OBJECTIVE: To evaluate whether hypercapnic acidosis attenuates acute alterations of pulmonary capillary permeability due to high lung stretch in rats using a simple, noninvasive, scintigraphic method. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Male adult Wistar rats weighing 291 +/- 7.5 g. INTERVENTIONS: Three groups of rats were studied: controls ventilated with a low (6 mL/kg body weight) tidal volume and rats ventilated with a high (38 mL/kg body weight) tidal volume under normocapnic (Paco(2) = 35.2 +/- 1.65 mm Hg) or hypercapnic (Paco(2) = 102.5 +/- 5.63 mm Hg) conditions. MEASUREMENTS AND MAIN RESULTS: Pulmonary capillary permeability alterations were assessed by monitoring the rate of (111)In-transferrin accumulation in lung tissue. Respiratory system pressure-volume curves were registered and analyzed. High tidal volume ventilation increased In-transferrin plasma to lung flux in such a way that I(111)In-transferrin behaved like a marker of water. The rate of initial (first 30 mins of high tidal volume ventilation) lung transferrin accumulation measured by scintigraphy (standardized lung/heart ratio) was steady, correlated with the percent decrease in respiratory system compliance (a marker of edema progression), and did not differ between normocapnic and hypercapnic groups (18.9 +/- 3.97 vs. 14.2 +/- 2.89%/hr, not significant). However, lung In-tranferrin accumulation rate was highly scattered due to variable interindividual mechanical properties of the respiratory system. This rate was correlated with initial values of volume of the upper inflection point of the pressure-volume curve (r = -.53, p < .001) and end-inspiratory pressure (r = .54, p < .001). Mechanical properties were similar in normocapnic and hypercapnic rats. There was no difference between In-transferrin accumulation rates in these rats when a stringent selection was made based on end-inspiratory pressure (28-32 cm H(2)O) or body weight (330-360 g). CONCLUSIONS: Hypercapnic acidosis does not influence in vivo the acute increase in pulmonary capillary permeability due to high-volume ventilation.

Acidosis, Respiratory↗
PubMed1983

Purification of a capillary permeability increasing-enzyme from the venom of Agkistrodon caliginosus (kankoku-mamushi).

A capillary permeability increasing-enzyme was purified from the venom of Agkistrodon caliginosus by gel-filtration on Sephadex G-100, ion exchange chromatographies on CM-Sephadex C-50 and DEAE-Sephadex A-50 and affinity chromatography on p-aminobenzamidine-epsilon-aminocaproic acid-Sepharose 4B. By this procedure, 6.2 mg of the purified enzyme was obtained from 4 g of the venom. The purified enzyme was homogeneous by disc electrophoresis at pH 8.3 and pH 4.5, and did not show any caseinolytic, clotting or bradykinin-releasing activities. The enzyme hydrolyzed N-alpha-tosyl-L-arginine methylester and the specific activity of the enzyme was 7.3 N-alpha-tosyl-L-arginine methylester units per mg of protein. When 3 micrograms of the enzyme was injected into the depilated skin of the back of a rabbit, capillary permeability was increased.

Animals↗
PubMed1991

Measurement of capillary permeability in canine heart determined by the tissue injection, residue detection method.

In previous studies the tissue injection, residue detection method failed to provide results of diffusional capillary permeability comparable to those of other methods. For this reason we reconsidered the kinetic theory and found that it is necessary to take into account the apparent (restricted) diffusion coefficient of the indicator within the tissue, D', in order to determine the permeability-surface area product, PdS = Vev.D.D'-1.tev-1 = Vev'.klo where D is the diffusion coefficient in free aqueous solution, Vev is the physical interstitial water volume of distribution, Vev' is the virtual (apparent) interstitial volume of distribution, tev is the mean transit time of the indicator, and klo is the recorded fractional initial washout rate constant. In experiments on open chest dog hearts we examined capillary permeability for 51Cr-EDTA and 99mTc-DTPA with the tissue injection, residue detection method and the single injection, residue detection method. Blood flow was measured independently with local 133Xenon washout. D and D' were measured by a true transient diffusion method. We found that the tissue injection, residue detection method gave results for capillary extraction and PdS-product similar to those obtained with a number of other methods based on indicator diffusion, so the tissue injection, residue detection method in its new kinetically correct formulation could prove useful in clinical studies of capillary permeability since it is applicable to determination of relative changes of permeability during interventional procedures.

Animals↗
PubMed2005

Mechanism of the effect of hydroxyethyl starch on reducing pulmonary capillary permeability in a rat model of sepsis.

Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. Recent studies have indicated that HES may reduce capillary leakage. The present in vivo study was performed to investigate the effects of HES on pulmonary capillary permeability, inflammatory mediators, and transcription factors in sepsis. Septic rats induced by cecal ligation and puncture (CLP) were treated with different doses of HES (7.5, 15, or 30 ml/kg, iv). At 5 or 12 hr after CLPq the rat lung tissues were collected. Pulmonary microvascular permeability, various cytokine levels (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6), mRNA expressions (cytokine-induced neutrophil chemoattractant (CINC), P-selectin, CD 11b/CD18 (Mac-1), and intercellular adhesion molecule-1 (ICAM-1)), and activities of nuclear factor (NF)-kappaB and activator protein (AP)-1 were determined in each group. HES, in a dose-related manner, significantly reduced pulmonary capillary permeability in the CLP model of sepsis. HES also down-regulated pulmonary proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6) and mRNA expressions (CINC and P-selectin), and inhibited pulmonary activities of NF-kappaB and AP-1. The results suggest that during sepsis HES reduces pulmonary capillary permeability and this beneficial effect of HES may act through down-regulation of inflammatory mediators and suppression of NF-kappaB and AP-1 activation.

Animals↗
PubMed1984

Studies on the transcapillary escape rate of fibrinogen and capillary permeability in patients with Plasmodium falciparum malaria.

The transcapillary escape rate and capillary permeability of fibrinogen were studied in 7 patients wih Plasmodium falciparum malaria and 4 control subjects by using 131I-fibrinogen as a tracer. The plasma disappearance curve of 131I-fibrinogen was followed during the first 60 minutes after injection. The mean transcapillary rate of fibrinogen in these patients was found to be significantly higher than that of the control group. As the plasma volume and fibrinogen concentrations were grossly elevated in these patients, this resulted in a significantly higher plasma clearance, intravascular pool of fibrinogen and out-flux of fibrinogen from the intravascular to the extravascular compartments. Both the effective capillary pore area per unit path length available for restricted diffusion and the specific permeability coefficient of plasma fibrinogen were increased in the patients group which indicated that the increased leakage of fibrinogen was due to the increased surface area of capillary membrane and an increased capillary permeability to fibrinogen. The mean extravascular transit time for fibrinogen to return to plasma via the lymph was slightly, but not significantly shorter in the patients group than the control group. All these findings indicated that there was an increased capillary permeability in patients with P. falciparum malaria which resulted in the increased leakage of plasma fibrinogen from the circulation into the extravascular space.

Adolescent↗
PubMed1990

Improvement of capillary permeability in patients with venous hypertension after treatment with TTFCA.

The VSC (vacuum suction chamber) device, a new system to evaluate local capillary permeability, was used with laser Doppler flowmetry to study variations of permeability and of the microcirculation in 10 normal subjects; in 22 patients with moderate, superficial venous hypertension; and in 12 patients with postphlebitic limbs and severe venous hypertension. All these patients had distal (ankle and foot edema) in the evening. After a first assessment these subjects were studied again after two weeks without treatment and after two weeks' treatment with total triterpenic fraction of centella asiatica (TTFCA), tablets, 60 mg, tid. The VSC produces a wheal on the skin of the perimalleolar region that disappears (in average) in less than sixty minutes in normal subjects. The disappearance time (DT) is greater in conditions of increased capillary filtration and permeability. The three groups of subjects (normal and those with superficial and severe venous hypertension) had significantly different, increasing disappearance time of the wheals at the first observation. There were no significant changes after two weeks' observation, but after 2 weeks' treatment with TTFCA, there was a significant decrease of DT both in limbs with superficial and with deep venous incompetence. The improvement (decrease) of the abnormally increased capillary permeability was associated with a significant improvement of the microcirculation and symptoms (studied by an analogue scale line). In conclusion this study showed a combined improvement of the microcirculation and capillary permeability after treatment with TTFCA and the possibility of using the VSC to evaluate the effects of drugs (or other treatment) on local capillary permeability in patients with venous hypertension.

Adult↗
PubMed1995

ANP increases capillary permeability to protein independent of perfusate protein composition.

In further studying hormonal regulation of microvascular exchange, we tested two hypotheses: 1) atrial natriuretic peptide (ANP) would increase capillary permeability to protein and 2) the actions of ANP on capillary permeability would be independent of the perfusate protein composition. These hypotheses were tested by assessing in situ capillary transport coefficients: hydraulic conductivity (Lp), apparent and diffusive permeabilities (Ps and Psd, respectively) to the protein alpha-lactalbumine, and convective coupling [Lp(1-sigma)] in mesenteric capillaries in cerebrally pithed frogs (Rana pipiens). The transport coefficients were determined in the absence and presence of frog ANP (fANP) during perfusion with either frog plasma or bovine serum albumin (BSA). Control Lp was 1.8-fold greater in vessels perfused with BSA compared with plasma. In the presence of 10 or 100 nM fANP, Lp was increased by approximately 3.5-fold in plasma-perfused vessels and approximately 2-fold in BSA-perfused vessels from their respective controls. Control Ps was 4.2-fold higher in vessels perfused with BSA compared with plasma. Despite the differences in control permeability, the increase in Ps by fANP was of similar magnitude (2- to 3-fold) for both protein perfusates. Analysis of the pressure-dependent alpha-lactalbumin flux suggested that the increase in capillary permeability induced by fANP is consistent with fANP increasing permeability without altering the selectivity of the capillary barrier.

Animals↗