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PubMed1979

Capillary permeability measured by bolus injection, residue and venous detection.

Kinetic analysis of residue and outflow curves of gamma-emitting indicators such as chromium-51-EDTA and iodide-131-thalamate from skeletal muscle gives the possibility to determine the extraction fraction and the plasma flow, and from these two values the capillary diffusion capacity can be calculated (Sejrsen 1970, preliminary report). This is possible both for the transport from blood to tissue and from tissue to blood. THis alternative method has been compared in the autoperfused cat gastrocnemius preparation with the indicator diffusion method based on venous registration of a diffusible test indicator and an intravascular reference indicator (Chinard et al. 1955, Crone 1963). The results of the five independent measurements show good agreement. Calculation of the permeability Pd based on a capillary surface area of 7 000 cm2/100 g of tissue gives values of 1.05 . 10(-5), 1.10 . 10(-5), and 1.16 . 10(-5) cm/s, which is in agreement with results obtained by other investigators. The permeability was equal in both directions, and thus the capillary membrane seems to function as a symmetrical membrane. Using an area of 5 000 cm2/100 g which presumably is more realistic at the plasma flow range used gives Pd values around 1.5 . 10(-5) cm/s. The effective pore area is calculated to constitute 1/50 000 of the capillary surface area. Calculation of volumes of distribution in the muscle tissue gave intravascular plasma volumes of 1.5 to 2.0 ml/100 g, an extravascular volume of 12.4 and 15.2 ml/100 g and a final monoexponential component constituting a compartment of 5.4 and 7.0 ml/100 g from residue and venous curves, respectively. The last mentioned compartment constitutes nearly 50 per cent of the extravascular space, and it is suggested, that it is located inside the sarcoplasmic reticulum, which anatomically constitutes about 50 per cent of the interstitial space. The total area of contact between the longitudinal and the transversal tubules in this subsystem, which is the membrane of the lateral saccus, is estimated to about 6 times the capillary surface area at a plasma flow of 15 ml/100 g . min which gives a permeability about 60 times lower for this membrane compared to the capillary membrane.

Animals↗
PubMed1976

Ultrastructural basis for alveolar-capillary permeability to protein.

The intravenous injection into mice of small volumes (less than 0.1 ml) of peroxidatic enzymes of molecular weight of 40 000 daltons or greater results in little if any penetration of these probe molecules into endothelial junctions. The injection of cytochrome c (12 000 daltons), on the other hand, results in the localization of this tracer in some but not all endothelial junctions. When horseradish peroxidase (EC 1.11.1.7) is injected in a large volume of saline (0.5 ml), reaction product is present in endothelial junctions and basement membrane, but is prevented from entering the alveolar space by zonulae occludentes between epithelial cells. These experiments indicate that although endothelial junctions, under physiological conditions, are largely impermeable to molecules the size of horseradish peroxidase, and presumably most serum proteins, they are labile and susceptible to stretching if intravascular pressure is increased. Freeze-fracture studies show that pulmonary capillary endothelial junctions are composed of one or at the most two strands which show areas of discontinuity. Epithelial junctions, by contrast, are composed of a continuous, complex network of anastomosing fibres. These observations confirm physiological experiments which indicate that it is the pulmonary epithelium rather than the endothelium which determines the permeability properties of the alveolar-capillary membrane to lipid-insoluble molecules. Bidirectional pinocytic transport is an additional mechanism whereby lipid-insoluble molecules are transported across both endothelial and epithelial layers. The relative contribution of this transport mechanism to the total amount transported remains to be established.

Animals↗
PubMed1981

Effects of histamine and histamine antagonists on intestinal capillary permeability.

Steady-state lymph flow, blood flow, and lymph and plasma total protein concentration were measured in an autoperfused cat ileum preparation during the continuous infusion of histamine at venous pressures of 0, 10, 20, and 30 mmHg. The capillary osmotic reflection coefficients for total proteins and each protein fraction were estimated. In addition, the ileum was pretreated with an H1-receptor antagonist (diphenhydramine) or with an H2-receptor antagonist (cimetidine). The results suggest that histamine selectively increases the ileal vascular permeability to plasma proteins of a molecular radius up to 96 A. The H1-receptor antagonist did not alter the histamine-induced permeability changes but did block the observed initial vasodilation. The H2-receptor antagonist significantly reduced the permeability changes associated with histamine while having only a slight effect on the initial vasodilation. It is concluded that the activation of H1-receptors is predominantly associated with the initial vasodilation, whereas the H2-receptors are predominantly associated with permeability.

Animals↗
PubMed1993

Albumin modulation of capillary permeability: role of endothelial cell [Ca2+]i.

Albumin is required in vascular perfusates to maintain the normal permeability of microvessel walls. The most common mechanism proposed for action of albumin involves binding to the endothelial cell surface to increase the resistance to water and solute flows through hydraulic pathways across the capillary wall. The results of the present experiments do not conform to this simple adsorption model. Ringer perfusion increased the hydraulic conductivity (Lp) of the wall of single perfused frog mesenteric microvessels by 4.0 +/- 0.5-fold. The increase in Lp was associated with an increase of cytoplasmic calcium concentration ([Ca2+]i) from 59 +/- 5 nM when albumin was in the perfusate to a transient peak of 181 +/- 13 nM, 1-2 min after Ringer perfusion. [Ca2+]i then fell back to close to 100 nM. Processes that reduced Ca2+ influx into endothelial cells (removal of extracellular Ca2+, membrane depolarization) reduced Ca2+ influx and attenuated the increase in [Ca2+]i. The same processes abolished the increase in Lp after Ringer perfusion and restored Lp to close to control values during Ringer perfusion. Thus Ca2+ entry into endothelial cells is required to initiate and maintain the increased permeability during Ringer perfusion.

Animals↗
PubMed1990

Capillary permeability: an albumin component attenuates active changes in Lp.

The mechanisms whereby atrial natriuretic peptide (AP) acutely and reversibly elevates hydraulic conductivity (Lp) are not known. This is the second of two studies of the influence of perfusate albumin composition on AP alterations in capillary Lp. In this study, we investigated the effect of dialysis of the perfusate albumin. A 2.2-fold increase in frog (Rana pipiens) mesenteric microvessel Lp occurred when 100 nM AP was added to the control perfusate containing dialyzed, crystallized bovine serum albumin (DXL-BSA 10 mg/ml; n = 20). By contrast, Lp was unchanged by 100 nM AP in 10 mg/ml untreated, crystallized BSA (XL-BSA; n = 8). The response to AP was unaltered at DXL-BSA contents of 10, 20, or 30 mg/ml (2.4-, 2.2-, and 3.1-fold, respectively; n = 8). Dialysis of the albumin, per se, did not influence control Lp (LpXL-BSA/LpDXL-BSA = 1.0; n = 5). The receptor-independent nitrovasodilator, sodium nitroprusside (SNP; 1 microM) elevated Lp by 1.7-fold in DXL-BSA (n = 30). The response was abolished in XL-BSA (n = 8). We conclude that small hydrophilic albumin-associated substances antagonize AP- and SNP-induced elevations of exchange microvessel hydraulic conductance without interfering with albumin's role in the maintenance of normal exchange vessel permeability.

Animals↗
PubMed1986

Studies on the transcapillary escape rate of albumin and capillary permeability in rhesus monkeys infected with Plasmodium knowlesi.

The transcapillary escape rate and plasma clearance rate of albumin were studied in five rhesus monkeys infected with Plasmodium knowlesi in comparison with six control monkeys by using 125I-HSA as a tracer. The plasma disappearance curve of the radioactivity was followed during the first 60 minutes after injection of this labelled protein. Plasma volume was found to be significantly higher while plasma albumin concentration was significantly lower, which resulted in the non-significantly increased intravascular albumin mass in the infected group. The mean values of the transcapillary escape rate, plasma clearance rate and the outflux of albumin from the intravascular to the extravascular compartments in the infected group were found to be significantly higher than those of the control group. This indicated that there was an increased leakage of plasma albumin from the circulation into the extravascular space in rhesus monkeys infected with P. knowlesi. As both capillary effective pore area per unit path length available for restricted diffusion and the specific permeability coefficient of plasma albumin were found to be significantly increased in the infected group, therefore the increased leakage of albumin was probably due to the increased surface of capillary membrane.

Animals↗
PubMed2000

Purified fumonisin B(1) decreases cardiovascular function but does not alter pulmonary capillary permeability in swine.

Fumonisins are mycotoxins produced by Fusarium verticillioides, which induce acute pulmonary edema in swine. We previously reported that ingestion of fumonisin-containing culture material decreases cardiovascular function in swine (1996,a,b; Fundam. Appl. Toxicol. 31, 169-172; 33, 140-148; 1999, Am. J Vet. Res. 60, 1291-1300). The main purpose of this study was to confirm that fumonisin B(1) was responsible for the observed cardiovascular changes. Treated pigs (n = 6) were given daily intravenous injections of purified fumonisin B(1) at 1 mg/kg for 4 days, while controls (n = 6) were injected with equal volumes of saline. On day 5, pigs were anesthetized with butorphanol-chloralose and instrumented for hemodynamic studies. Terminally, bronchoalveolar lavage was performed on each pig to determine the relative permeability index of the pulmonary endothelium. Fumonisin B(1)-treated pigs had marked decreases in the maximal rate of change of left ventricular pressure (dP/dt(max)), mean aortic pressure, cardiac output, and arterial pO(2), accompanied by increases in mean pulmonary artery pressure, oxygen extraction ratio, and blood hemoglobin concentration. Plasma and left ventricular sphingosine and sphinganine concentrations were markedly increased in treated pigs at day 5; however, there was no difference in the relative permeability index between groups. Serum cholesterol concentrations and activities of hepatic-derived enzymes were increased, and hepatocyte apoptosis and mitoses were present in the livers of fumonisin-treated pigs. In the lungs of treated pigs, there was proteinaceous edema and membranous accumulations in capillary endothelial cells. These results indicate that cardiovascular function is altered by fumonisin B(1), and that fumonisin-induced pulmonary edema is caused by left-sided heart failure and not by altered endothelial permeability. Because of the potential for contamination of human foodstuffs by fumonisins, the cardiovascular toxicity of these compounds must be taken into consideration.

Animals↗
PubMed1978

[The influence of capillary permeability on the extravascular protein quantities as measured in situ (author's transl)].

The extravascular protein contents in the perivascular connective tissue of a rat's mesenterial plate was measured ultramicrospectrophotometrically in situ and in vivo after changing the hydrostatic and colloidosmotic pressures of the blood. We analized the perivascular area of the different microcirculatory vessels, arterioles, capillaries and venules. The perivascular protein contents, which corresponds besides arterioles to 40% and besides venules to 59% in comparison to the intravascular blood plasma, decreased in a comparison group under the osmotic influence of the perfusion liquid on the mesenterial plate. An injection of an isotonic saline solution is followed only by small fluctuations of the perivascular protein contents during one hour. After blood loss a transitional increase of extravascular protein at the perivenular area was observed indicating the mobilisation of protein depots. Around arterioles the extravascular protein contents did not change significantly. An intravenous injection of albumin solution was followed by a short-termed increase of tissue protein around the arterioles. Around the venules after 50 minutes the extravascular protein contents increased significantly. Within one hour after the changes of the permeability conditions the maximal induceable protein movements in the perivascular space were calculated as +/- 1.35 g% plasma protein concentration corresponding to a maximun protein exchange of +/- 3.1 mg ml(-1) tissue.

Animals↗
PubMed1983

Dog lymph flow in increased capillary permeability states.

The lung lymph flow rate (QL) is increased in edema caused by an increase in lung microvascular permeability. This increase in QL could be caused by either a decrease in the effective resistance of the lymph vessels (RL), or by an increase in the effective lymph driving pressure (PL), or by a change in both RL and PL. We estimated PL and RL from the linear relationship between QL and the pressure at the outflow end (PO) of five cannulated dog lung lymph vessels (RL = - delta Po/delta QL and PL = the PO at which QL = 0). We increased lung microvascular permeability by giving the dogs 100 mg/kg of alloxan and found that QL increased from 24.5 +/- 8.9 microliters/min to 112 +/- 41 microliters/min (mean +/- SD). RL decreased from 0.35 +/- 0.12 to 0.11 +/- 0.04 cm H2O min/microliters and PL increased from 8.5 +/- 1.5 to 15.9 +/- 2.7 cm H2O. We then increased the capillary pressures from 18.3 +/- 3.8 to 41.3 +/- 7.3 cm H2O and QL increased to 169.9 +/- 47.8 microliters/min. PL increased by an additional 6.3 cm H2O but RL decreased by only an additional 0.02 cm H2O min/microliters. These results show that the QL vs PO relationship is changed in edema secondary to an increase in microvascular permeability, and that this change can be represented as changes in RL and PL. In terms of these parameters, QL increased in edema as a result of a decrease in RL and an increase in PL.

Alloxan↗
PubMed2006

Effect on capillary permeability in rabbits of iridoids from Buddleia scordioides.

The methanol soluble fraction of the leaves of Buddleia scordioides after column chromatography resulted in the isolation of two known iridoid glucosides, catalpol and methylcatalpol. The structures were elucidated by extensive 1D-2D-NMR spectroscopy. The structure of methylcatalpol was confirmed by single-crystal x-ray diffraction. These compounds showed protective activity against increased (both chloroform and histamine) skin vascular permeability in rabbits. The protective effect was measured as the reduction in leakage of Evans blue. The results showed that the iridoids produced a significant inhibition of microvascular permeability. A comparison was made between the action of the iridoids and a known inhibitor of vascular permeability, troxerutin (50 mg/kg). Methylcatalpol and catalpol were found to be less effective than troxerutin.

Animals↗
PubMed1986

[Ultrastructure of capillary permeability in human brain tumors--4: Cerebral edema associated with meningiomas].

The cerebral edema, as judged by computed tomographic scan, associated with supratentorial meningiomas was assessed in 43 cases. No relationship to the occurrence or the degree of edema could be established with respect to meningioma location and histological type. The larger the meningioma, the more likely the presence of and the severity of cerebral edema. The materials were obtained from surgically removed specimens in 6 cases of meningiomas with and without associated cerebral edema, and tumor vessels were studied with conventional ultrathin section and freeze-fracture replica techniques. The characteristic findings of these tumor vessels were thinning of endothelium and many fenestrations, short and in fact open tight junctions. Tight junctions between endothelial cells were composed of one or two strands which appeared to be a discontinuous array of particles. The ultrastructural appearance of tumor vessels is similar to that seen in meningiomas with and without associated cerebral edema.

Adolescent↗
PubMed1987

Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study.

Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity.

Acute Disease↗