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PubMed1983

Permeability of single capillaries to intermediate-sized colored solutes.

The fiber matrix theory of capillary permeability was evaluated by measuring permeability coefficients to colored solutes with Stokes radii between 0.5 and 1.76 nm. In vivo calibration of a microscope photometer established the range of linearity for optical density measurements from a rectangular window that included the test capillary and surrounding tissue. In individually perfused capillaries of frog mesentery the following permeability coefficients, expressed as mean +/- SE X 10(5) cm/s were obtained: azure C (mol wt 277), 11.0 +/- 0.2; patent blue violet (566), 3.95 +/- 0.67; Evans blue (960), 1.15 +/- 0.23; microperoxidase (1,900), 1.13 +/- 0.31; and FITC-dextran 3 (3,400), 0.48 +/- 0.18. There is significant restriction to diffusion of all solutes larger than azure C. Fibers 0.5 nm in radius occupying 8.5% of the volume of intercellular junctions (area 2.2 X 10(-3) cm2/cm2, depth 0.6 X 10(-4) cm) account for the 22-fold range of measured permeabilities. The fiber density estimated is larger than that required to describe water flow through the junction. Negative charges on solutes larger than 0.5 nm radius may contribute to exclusion and restriction to diffusion in intercellular junctions.

Animals↗
PubMed1997

Low-dose prostacyclin has potent capillary permeability-reducing effect in cat skeletal muscle in vivo.

The dose-response effects of intravenous infusion of prostacyclin on capillary permeability (the capillary filtration coefficient technique), hydrostatic capillary pressure, transcapillary filtration, and vascular tone were analyzed in vivo on cat skeletal muscle from a normal and an increased permeability level. Increased permeability was accomplished by intra-arterial infusion of tumor necrosis factor-alpha or histamine. Permeability effects of bradykinin were also analyzed. Prostacyclin decreased capillary permeability by 8% at a dose of 0.1 ng.kg-1.min-1 and at most by 30% below control attained at 2 ng.kg-1.min-1, also with no effect on vascular tone and hydrostatic capillary pressure. The permeability increase by tumor necrosis factor-alpha and histamine (by 54 and 73%) was more than counteracted by the simultaneous infusion of prostacyclin at 2 ng.kg-1.min-1. The vasodilator effect of tumor necrosis factor-alpha was also restituted. Indomethacin (prostacyclin inhibitor)-induced increase in capillary permeability (25%) was more than restituted by prostacyclin at 2 ng.kg-1.min-1. Surprisingly, bradykinin decreased capillary permeability. We conclude that endogenous prostacyclin may be a physiological regulator of capillary permeability and that low-dose prostacyclin infusion may have clinical relevance in states of increased permeability.

Animals↗
PubMed1981

Superoxide radicals in feline intestinal ischemia.

One hour of regional ischemia significantly increases the permeability of intestinal capillaries. The role of local humoral agents in the genesis of an increased capillary permeability in the ischemic bowel was assessed using specific antagonists to substances commonly believed to be involved in the pathogenesis of ischemic states. Capillary permeability estimates in autoperfused segments of cat ileum were derived from the relationship between lymph-to-plasma protein concentration ratio and lymph flow. Pretreatment of the ileal segments with either benadryl + cimetidine, indomethacin, or methylprednisolone did not significantly alter the permeability increase induced by regional ischemia. Pretreatment with superoxide dismutase (SOD), a superoxide radical scavenging enzyme, significantly attenuated the capillary permeability change induced by regional ischemia. Intravenous E. coli endotoxin administration in normotensive preparations increased intestinal capillary permeability; however, lethal doses of the endotoxin were required. The results of this study indicate that superoxide radicals are primarily responsible for the increased capillary permeability in the ischemic bowel.

Animals↗
PubMedDate not supplied

Optical and radioisotope indicator dilution measurements in pulmonary edema.

The objective of this study was a validation of an optical multiple indicator dilution technique for measuring microvascular exchange parameters in edematous lungs by comparison to conventional radioisotope multiple indicator dilution methods. Six anesthetized dogs were studied at baseline and after alloxan infusion to increase capillary permeability. In addition, 11 isolated, perfused dog lungs were studied at baseline and after edema was created by increasing venous pressure or by infusing alloxan to increase vascular permeability. Increased capillary permeability from alloxan infusion led to increases in most but not all capillary exchange parameters as analyzed by mathematical models and measured by both optical and radioisotope methods. Increased vascular pressure led to increased edema but no significant increases in capillary exchange parameters. Two-way analysis of variance (ANOVA; variations in baseline versus pressure or alloxan and variation in optical versus radioisotope for each transport parameter derived from the mathematical models) indicated few significant differences in capillary exchange parameters between optical and radioisotope measures. Newman-Keuls multiple comparison tests did uncover some variations between a few of the group-mean values derived from optical and radioisotope methods. However, optical and radioisotope parameter measurements were highly correlated for all studies regardless of the mathematical model used for analysis.

Alloxan↗
PubMed1985

Permeability of materials in postglomerular capillary bed and distribution to interstitium of kidney in rats.

Extracellular reference materials are necessary to estimate tubular transport parameters for drugs which are secreted in the kidney. They must set up the flow-limited distribution between plasma and interstitial space, not be distributed to the intracellular space, and be nondegradable in the extracellular space. The capillary permeability of various molecular weight markers in the post glomerular circulation was investigated by performing pulse-injection multiple indicator dilution experiments on isolated rat kidney, using simultaneous injection of T1824-labeled albumin (the plasma reference) and creatinine (or inulin) as the extracellular reference materials. The permeability constants and the gamma values (ratio of the volume in the space of interstitium to that of capillary plasma) for creatinine and inulin were calculated by a nonlinear least squares regression. The gamma values for creatinine were greater than those for inulin, implying that the volume of distribution for creatinine is different from that for inulin. The capillary permeability clearance (CLinflux) for creatinine was 4 times higher than that of inulin, and was 3 times greater than the perfusion rate. Thus, creatinine satisfies the qualification for the flow-limited distribution between plasma and interstitial space. These findings suggest that in the rat kidney creatinine is more suitable for the extracellular reference material than inulin.

Animals↗
PubMed1985

The effects of native and modified bovine serum albumin on the permeability of frog mesenteric capillaries.

Single capillaries in the mesenteries of pithed frogs were perfused sequentially with two frog Ringer solutions. The first solution contained no protein; the second solution contained either native or chemically modified bovine serum albumin (BSA) at a concentration of 3-5 mg ml-1. During each perfusion capillary permeability was assessed from the hydraulic conductivity of the capillary wall (Lp) which was determined from measurements of fluid filtration rate at two or more different capillary pressures (Michel, Mason, Curry, Tooke & Hunter, 1974). Lp measured during perfusion with protein-free Ringer solution was on average three times greater than its value for the same vessel perfused with Ringer solution containing native BSA. This confirms the findings of Mason, Curry & Michel (1977). BSA, which had been succinylated to modify the free amino groups of its lysine residues, appeared to be as effective as native BSA in reducing Lp. After modification of its arginine side chains by exposure to 1,2-cyclohexanedione (CHD) in the presence of 0.2 M-NaOH, BSA lost its property of reducing Lp in capillaries perfused with Ringer solution. Exposure of BSA to 0.2 M-NaOH followed by dialysis against normal Ringer solution did not affect its property of reducing Lp. CHD-treated BSA at a concentration of 2.5 mg ml-1 had no effect upon the effective osmotic pressure exerted across capillary walls by Ringer perfusates containing the neutral polymer Ficoll 70 at a concentration of 40 mg ml-1. Native BSA raised the effective osmotic pressure from 7.07 +/- 1.93 cmH2O to 20.50 +/- 2.37 cmH2O (n = 7; P less than 0.001). It is concluded that the effects of BSA on permeability depend upon specific sites in the BSA molecule. It is suggested that these sites involve positively charged arginine side chains of the albumin molecule. The results are discussed in terms of the fibre-matrix hypothesis of capillary permeability and in terms of Brown's (1976) theory for the structure of albumin.

Animals↗
PubMed1997

Exogenous human recombinant interleukin-10 attenuates hindlimb ischemia-reperfusion injury.

Proinflammatory cytokines have been found to mediate part of the local and distant organ injury after ischemia and reperfusion (I/R). The anti-inflammatory cytokine interleukin-10 (IL-10) inhibits both TNF-alpha and IL-1, and we hypothesized that exogenous human IL-10 may decrease lung and soleus muscle injury after hindlimb I/R. Male Sprague-Dawley rats were randomly assigned to I/R (n = 10); I/R+IL-10 (10 micrograms i.v., n = 10), SHAM (n = 4); or SHAM+IL-10 (10 micrograms i.v., n = 4). Bilateral hindlimb ischemia was produced by tourniquet occlusion for 4 hr and all animals were sacrificed after 4 hr of reperfusion or at comparable times for the SHAMs. Soleus muscle cellular injury was determined by uptake of 99Tc pyrophosphate while soleus muscle capillary permeability, and lung capillary permeability were assessed by uptake of 125I-labeled albumin. Soleus muscle and lung neutrophil infiltration were measured with the myeloperoxidase assay. Serum samples were assessed for TNF-alpha production with the WEHI bioassay. Hindlimb I/R caused significant soleus muscle cellular injury, soleus muscle capillary injury, lung capillary injury, and lung neutrophil infiltration, Pretreatment with exogenous IL-10 significantly reduced soleus muscle capillary permeability and also reduced soleus muscle cellular injury, but not to a statistically significant degree. IL-10 administration also reduced pulmonary capillary permeability despite significantly increased lung neutrophil infiltration. Elevated TNF-alpha levels were found in 66% (4/6) rats in the I/R group versus 30% (3/10) rats in the I/R+IL-10 group. Exogenous IL-10 attenuates both local and distant organ injury after hindlimb I/R potentially independent of neutrophil infiltration.

Animals↗
PubMed1990

Permeability of frog mesenteric capillaries after partial pronase digestion of the endothelial glycocalyx.

1. The proteolytic enzyme pronase, which degrades the endothelial cell glycocalyx, was perfused through single capillaries of frog mesentery. Hydraulic conductivity (Lp) of each vessel was determined before and after pronase perfusion. In three vessels in which Lp increased, the ultrastructure of interendothelial clefts was examined. In a separate group of frogs the effect of pronase on the endothelial glycocalyx was assessed by using cationized ferritin to label the capillary luminal surface. 2. Control Lp was 2.0 x 10(-7) cm s-1 cmH2O-1 (10 mg ml-1 bovine serum albumin, BSA, in frog Ringer solution). Vessels were then perfused with a solution containing 0.1 mg ml-1 pronase and 10 mg ml-1 BSA for 1 min. Lp measured in the same eleven vessels increased to 4.9 x 10(-7) cm s-1 cmH2O-1 (P less than 0.005). 3. Transverse sections of three of these vessels were examined by transmission electron microscopy at eight sites along each vessel. In these sections a total of 156 interendothelial cell clefts were found and photographed. No morphological features, such as fenestrations, transendothelial channels, or intercellular gaps associated with inflammation, were found which might account for the increases in Lp. 4. Measurement of cleft dimensions yielded a harmonic mean cleft depth (delta x) of 0.32 microns and an arithmetic mean cleft depth of 0.64 microns. Mean width (w) of the clefts outside the tight regions was 0.012 microns and the cleft length per unit area (L) was 1330 cm-1. The mean fractional pore area of vessel wall per unit cleft depth, Ap/delta x, calculated as Lw/delta x, was 48.7 cm-1. 5. There was less cationic ferritin (CF) labelling of the luminal glycocalyx in pronase-perfused than in control capillaries. On average, the proportion of the luminal surface covered by CF was 85% in controls and 42% in pronase-treated capillaries (P less than 0.01). In some vessels the CF pattern was greatly disrupted, indicating large changes in the glycocalyx structure. 6. It is concluded that the moderate increases in Lp induced by pronase perfusion are associated with partial digestion of the endothelial glycocalyx but are not accompanied by changes in the dimensions of the intercellular cleft. These observations support the fibre matrix hypothesis of capillary permeability and suggest that the endothelial glycocalyx contributes as much as 60% of the hydraulic resistance of the capillary wall.

Animals↗
PubMed1982

Fine structure and permeability of capillaries in the stria vascularis and spiral ligament of the inner ear of the guinea pig.

The blood capillaries in the stria vascularis and the spiral ligaments of guinea pigs were studied by electron microscopy with freeze-fracture and thin section methods, including tracer experiments with horseradish peroxidase (HRP) and microperoxidase (MP). The endothelial cells of the capillaries of both tissues are connected by tight junctions, and contain about the same number of micropinocytotic vesicles. In cases of intravascular administration before fixation, both of the tracers stained the perivascular space and almost all endothelial vesicles in the stria vascularis. On the other hand, the perivascular space and many vesicles in the spinal ligament were unstained. The endothelial tight junctions in the stria vascularis prevented the penetration of HRP, but sometimes allowed the penetration of MP. Those of the spiral ligament were impermeable to both tracers. In cases of tracer administration after fixation, leakage spots of HRP from capillaries were sparsely located all over the stria vascularis. Transendothelial channels and isolated fenestrae formed by micropinocytotic vesicles were detected. It is concluded that the capillaries of the stria vascularis are similar to the muscle capillaries and to the capillaries of the elasmobranch brain, whereas those in the spiral ligament are similar to the brain capillaries of higher vertebrates.

Animals↗