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PubMed2001

MRI assessment of microvascular characteristics in experimental breast tumors using a new blood pool contrast agent (MS-325) with correlations to histopathology.

A new contrast medium, MS-325, was compared to albumin-(Gd-DTPA)(30) in 18 chemically induced rat breast tumors based on quantitative estimates of microvascular permeability (K(PS)) and fractional plasma volume (fPV) using a two-compartment bidirectional model. No significant correlation was found between MS-325-enhanced microvascular assays with either tumor grade or with microvascular counts (MVCs). In comparison, the correlation coefficient between K(PS) and histologic tumor grade using albumin-(Gd-DTPA)(30) (r =.58) was statistically significant (P <.01). Also, using albumin-(Gd-DTPA)(30), a significant correlation (r =.55, P <.05) was observed between the K(PS) and MVC, a biomarker of angiogenesis. Correlations between fPV and MVC were not statistically significant for either contrast medium. In conclusion, using MS-325, no significant correlations between the MR-estimated permeability values or plasma volumes were observed in experimental breast tumors with either the histologic tumor grade or MVC. This analysis confirms our previous determination that capillary permeability estimates, using a prototype large molecular contrast medium, albumin-(Gd-DTPA)(30), correlate significantly with both histologic tumor grade and MVC.

Animals↗
PubMed1976

Tannic acid as an electron-dense probe in the testis.

The use of tannic acid to preserve and promote the staining of protein constituents of the extracellular fluid is described. Its usefulness for delineating the extracellular compartment and detecting changes in capillary permeability is illustrated in experiments on the testis.

Animals↗
PubMed1987

Type 2 diabetes. Primary vascular disorder with metabolic symptoms?

It is postulated that in the resting state insulin-dependent tissue uptake of glucose is limited by the rate of blood flow, capillary permeability, and the number of perfused capillaries in the skeletal muscles. A mathematical model, simulating these relations, is developed. According to this model, changes in the indicated parameters might cause type 2 diabetes.

Biological Transport, Active↗
PubMedDate not supplied

Fluid flow and reactive transport around potential nuclear waste emplacement tunnels at Yucca Mountain, Nevada.

The evolution of fluid chemistry and mineral alteration around a potential waste emplacement tunnel (drift) is evaluated using numerical modeling. The model considers the flow of water, gas, and heat, plus reactions between minerals, CO(2) gas, and aqueous species, and porosity-permeability-capillary pressure coupling for a dual permeability (fractures and matrix) medium. Two possible operating temperature modes are investigated: a "high-temperature" case with temperatures exceeding the boiling point of water for several hundred years, and a "low-temperature" case with temperatures remaining below boiling for the entire life of the repository. In both cases, possible seepage waters are characterized by dilute to moderate salinities and mildly alkaline pH values. These trends in fluid composition and mineral alteration are controlled by various coupled mechanisms. For example, upon heating and boiling, CO(2) exsolution from pore waters raises pH and causes calcite precipitation. In condensation zones, this CO(2) redissolves, resulting in a decrease in pH that causes calcite dissolution and enhances feldspar alteration to clays. Heat also enhances dissolution of wall rock minerals leading to elevated silica concentrations. Amorphous silica precipitates through evaporative concentration caused by boiling in the high-temperature case, but does not precipitate in the low-temperature case. Some alteration of feldspars to clays and zeolites is predicted in the high-temperature case. In both cases, calcite precipitates when percolating waters are heated near the drift. The predicted porosity decrease around drifts in the high-temperature case (several percent of the fracture volume) is larger by at least one order of magnitude than in the low temperature case. Although there are important differences between the two investigated temperature modes in the predicted evolution of fluid compositions and mineral alteration around drifts, these differences are largely within to the model uncertainty and the variability of water compositions at Yucca Mountain.

Carbon Dioxide↗
PubMed1994

Antihistaminergic pretreatment prevents tissue extravasation of albumin from intra-abdominal trauma in rats.

Intra-abdominal surgery causes a loss of plasma into tissues within and around the abdomen, endangering tissue viability. Mast cells, containing histamine, are abundant in the abdominal cavity. In a model of mechanical intra-abdominal trauma, we investigated whether pretreatment with histaminergic H1 and H2 receptor blockers counteracts this extravasation. In Wistar rats under chloralose anaesthesia, tissue clearances of labelled albumin were determined by a double isotope technique. Four groups were studied: Traumatized rats, pretreated (n = 10) and non-pretreated (n = 9): non-traumatized rats; pretreated (n = 10) and non-pretreated (n = 9). In the traumatized rats, given pyrilamine 10 mg kg-1 (H1) plus cimetidine 25 mg kg-1 (H2) just before the trauma, the blockers prevented the haemoconcentration from loss of plasma and the drop in arterial pressure during the very trauma procedure, observed among non-pretreated rats. Furthermore, they significantly decreased the clearance of albumin in the abdominal wall and the pancreas. In the non-traumatized animals, the blockers lowered arterial pressure and heart rate. In conclusion, the anti-histaminergic pretreatment decreased the trauma induced leakage of albumin, by mechanisms which may involve readjustments of pressures and flows in capillaries as well as a prevention of histamine effects on capillary permeability.

Abdominal Injuries↗
PubMed1991

Differentiation of capillary leak and hydrostatic pulmonary edema with a macromolecular MR imaging contrast agent.

The ability of a macromolecular contrast agent (polylysine-[gadopentetate dimeglumine]40) to allow distinction of pulmonary capillary leak from hydrostatic pulmonary edema was investigated. Capillary leak edema was induced in 12 rats by means of venous injection of oleic acid; hydrostatic pulmonary edema was induced in 10 rats by means of continuous infusion of 0.9% sodium chloride. In the oleic acid pulmonary edema model, the signal intensity continued to increase for 12 minutes after administration of contrast material, indicating a leak of paramagnetic molecules from the intravascular to the extravascular spaces. Conversely, lung enhancement remained virtually constant after injection of contrast material in the hydrostatic edema model, as would be expected in the absence of endothelial damage. Hydrostatic edema tended to be distributed homogeneously throughout the lung, while capillary leak edema tended to occur predominantly in the peripheral portions of the lung. These findings indicate that macromolecular contrast agents can facilitate differentiation between edema caused by elevated intravascular pressure and edema induced by abnormal capillary permeability.

Animals↗
PubMed1976

Hemodynamic and alveolar protein studies in noncardiac pulmonary edema.

Hemodynamic data were obtained within 15 hours of admission in 11 previously healthy patients (20 to 51 years of age, 7 men and 4 women) who had developed transient, reversible pulmonary edema without cardiac dilation in association with near-death from freshwater drowning (2 cases), pentobarbital overdose, heroin overdose (2 cases), smoke inhalation, chest trauma, sepsis (2 cases), pancreatitis, or prolonged abdominal surgery with suspected sepsis. Using a balloon-tipped flow-directed catheter, the pulmonary artery systolic/diastolic pressures (in mm Hg) were 25/12, 22/9, 31/11, 26/15, 20/10, 35/15, 40/15, 32/18, 20/10, 24/10, and 20/7; the corresponding pulmonary capillary wedge pressures (in mm Hg) were 8, 9, 6, 14, 6, 6, 15, 15, 10, 10, and 5, respectively. Plasma colloidal osmotic pressures measured in the latter 5 cases were 26, 18, 18, 18, and 15 mm Hg, respectively. In addition, the protein content of the alveolar fluid was 5.1, 3.4, 4.0, and 7.1 g per 100 ml in 4 patients. The concentration and distribution of the protein in plasma and alveolar fluid were very similar. These findings provide strong efidence that altered capillary permeability is responsible for the pulmonary edema.

Blood Pressure↗
PubMed1986

Microscopic peliosis of pancreatic islets in a woman with MEN-1 syndrome.

We report herein a case of histologically identified peliosis of pancreatic islets in the surgically removed portion of the pancreas of a 30-year-old woman with multiple endocrine neoplasm, type 1 (MEN-1) syndrome. In addition to microscopic peliosis, the pancreas contained multiple endocrine tumors producing insulin, glucagon, somatostatin, and growth hormone-releasing factor and showed evidence of widespread nesidioblastosis. It is uncertain whether peliosis of pancreatic islets and MEN-1 syndrome were coincidental or whether the two diseases were causally related. Since hormonal factors can result in hepatic peliosis, it is tempting to speculate that the endocrine imbalance secondary to MEN-1 syndrome might have played a role in the genesis of peliosis in this case. Although no direct proof of vascular damage was encountered, it is conceivable that escape of red blood cells from the circulation and their accumulation in tissue spaces was due to abnormal islet blood flow and increased capillary permeability.

Adult↗
PubMed1988

Effects of fenoldopam on feline intestinal microcirculation.

Experiments were performed to evaluate the effects of the specific dopamine-1-receptor agonist, fenoldopam, on the feline intestinal microcirculation. Cranial mesenteric arterial pressure, cranial mesenteric vein pressure, cranial mesenteric vein blood flow, venous occlusion capillary pressure, pre- and postcapillary resistances, total mesenteric vascular resistance, lymph flow, lymph and plasma protein concentrations, the capillary osmotic reflection coefficient, and the capillary filtration coefficient were determined in an isolated autoperfused jejunal segment in anesthetized fasted cats during intra-arterial administration of saline or fenoldopam mesylate in saline. Fenoldopam significantly increased mean cranial mesenteric vein blood flow from 26.8 +/- 3.4 to 33.7 +/- 2.8 ml.min-1.100 g-1. This increase in blood flow was due primarily to a significant decrease in mean intestinal vascular resistance from 3.14 +/- 0.32 to 2.54 +/- 0.2 mm Hg.ml-1.min-1.100 g-1, since cranial mesenteric arterial pressure during fenoldopam infusion was not different from the value obtained during control studies. Mean capillary pressure during fenoldopam infusion (17.2 +/- 0.5 mm Hg) was significantly greater than mean capillary pressure during control studies (15.6 +/- 0.3 mm Hg). The mean lymph flow during fenoldopam infusion (0.186 +/- 0.083 g/dl) was significantly greater than the value obtained during saline infusion (0.08 +/- 0.009 g/dl). Fenoldopam infusion significantly increased the mean capillary filtration coefficient from 0.135 +/- 0.021 to 0.275 +/- 0.035 ml.min-1.100 g-1.mm Hg-1 without altering the capillary osmotic reflection coefficient. These results suggest that specific dopamine-1-receptor stimulation in the small intestine increases the perfused capillary density without altering capillary permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Glomerular and postglomerular transcapillary exchange in dog kidney.

The multiple-indicator dilution technique (MIDT) was used to study glomerular and postglomerular permselectivity to neutral dextran molecular weight markers in anesthetized dogs undergoing mannitol diuresis. Renal vein and urine outflow curves were obtained after an intraarterial pulse injection of 125I-labeled albumin (plasma reference), creatinine (extracellular reference), [14C]inulin, and chromatographically homogeneous 3H-labeled neutral dextrans. The urine recovery data reflect solute losses across the glomerulus. The renal vein outflow curves contain information about both glomerular and postglomerular extraction. For dextrans less than 13,500 daltons the urine transit pattern was superimposed on the glomerular markers creatinine and inulin. Relative to 125I-labeled albumin, the renal vein recoveries for creatinine, inulin, and dextrans (less than 13,500 daltons) were all equal. The renal vein mean transit time (tdextran) was greater than talbumin and less than tcreatinine. With increasing dextran size, tdextran progressively decreased. Eventually for dextrans greater than 15,500 daltons, tdextran became equal to talbumin in the renal vein, whereas urine recovery relative to inulin decreased with increasing size. Urine recovery of 3H-labeled dextran (ED) relative to inulin (Ei) provided a measure of unidirectional fractional glomerular extraction (ED/Ei). Constant infusion fractional clearance measurement of the same dextrans [U/P)D/(U/P)i) was found to equal ED/Ei obtained from the MIDT. Within the autoregulatory range of glomerular filtration, ED/Ei was invariant with reduction in renal plasma flow. Therefore, under the experimental conditions employed in the present study, diffusion across the glomerulus was negligible relative to convection. This permitted estimation of the reflection coefficients for the series of neutral dextrans. Postglomerular extraction was markedly flow dependent, which implies a major diffusion limitation. Application of a barrier-limited distributed model permitted quantitation of postglomerular capillary permeability coefficients for neutral markers of less than 5000 daltons.

Capillary Permeability↗
PubMed1993

[Damage caused by monoclonal immunoglobulins and possibilities of therapy. 2].

Monoclonal immunoglobulins (M-Ig) cause due to their chemical structure and physical properties some pathological manifestations. In the text all skin changes are analyzed which are supposed to be associated with M-Ig. Some light chains form amyloid masses which can damage almost all organs. M-Ig can perhaps enhance also the capillary permeability although their role in the capillary leak syndrome remains obscure.

Humans↗
PubMed1989

Proposed role for leukotrienes in the pathophysiology of multiple systems organ failure.

The leukotrienes are a group of biologically active products of arachidonic acid metabolism that have been demonstrated to possess the capability to alter vascular reactivity as well as vascular permeability when applied topically to tissues or infused into the vascular bed of various organs. These biologic effects of the exogenous leukotrienes have led to the speculation that these arachidonic acid metabolites could be important mediators in the pathophysiologic events that culminate in the development of acute lung injury and MSOF. Increased production of inflammatory mediators is undoubtedly a contributing factor to the pathophysiologic events that culminate in MSOF. LTB4 has been shown to be a potent stimulator of neutrophil chemotaxis and adhesion. It is possible that LTB4 may be responsible for initiation or amplification of the inflammatory response in this syndrome. The sulfidopeptide leukotrienes have profound effects on cardiac function, which may be mediated through effects on both coronary blood flow and cardiac contractility. These arachidonic acid metabolites are also capable of altering blood flow to several vascular beds and, when synthesized endogenously and released, may be important in the regulation of the peripheral circulation. Endogenous leukotrienes may have physiologic or pathophysiologic effects on cardiac output and its distribution to peripheral vascular beds or on systemic blood pressure. In view of the observations that alterations in cardiac output, blood pressure, and individual organ blood flow have been demonstrated in the clinical setting of ARDs and MSOF, it is attractive to suggest that the leukotrienes may contribute to the hemodynamic alterations observed in these clinical conditions. In addition to their effects on vascular smooth muscle and the myocardium, the leukotrienes have been shown to increase the permeability of blood vessels. In the case of the sulfidopeptide leukotrienes, the enhanced vascular permeability appears to be a direct effect of these lipoxygenase metabolites. Although LTB4 may directly increase vascular permeability, several lines of evidence suggest that the recruitment and activity of neutrophils is required for edema formation to develop following application of this leukotriene. Enhanced capillary permeability, at least in the pulmonary circulation, is a hallmark of ARDS and is also frequently present in MSOF. The leukotrienes, either through direct effects on vessels or through recruitment of inflammatory cells, are likely contributors to the nonhydrostatic edema associated with these syndromes.

Animals↗
PubMed1993

Interstitial lactate and glucose concentrations of the isolated perfused rat heart before, during and after anoxia.

In isolated rat hearts perfused according to the Langendorff technique lactate and glucose concentrations were determined in the interstitial transudate and the venous effluent before, during and after periods of 15 or 30 min anoxia. The interstitial transudate emerged at the surface of the heart as a result of albumin-free perfusion. During normoxic perfusion the interstitial lactate concentration was 0.144 +/- 0.025 mmol/l (n = 6); the venous lactate concentration was 0.033 +/- 0.005 mmol/l. From the interstitial and the mean vascular concentration, together with the lactate release and the glucose uptake, the apparent permeability surface area products (P.S product) were calculated using Fick's law. The apparent P.S products for lactate and glucose were 4.6 and 3.9 ml/(min x g), respectively. During anoxia we measured a four- to sixfold increase of the interstitial lactate concentration. At the end of the anoxic periods the apparent P.S product was two- to threefold higher than during normoxia; the apparent glucose P.S product increased about fourfold. After 15 min anoxia the increases of permeability were completely reversed in the reoxygenation period. However, after a period of 30 min anoxia the apparent P.S products for lactate and glucose remained raised, which means that there was a prolonged or even irreversible increase of capillary permeability. Besides the marked transcapillary concentration difference for lactate, these data show prolonged functional alteration of the capillary wall after 30 min anoxia.

Animals↗
PubMed1983

[Status of cerebral capillary circulation during ischemia with barbiturate protection].

Experiments on 78 albino rats with ligated common carotid arteries were carried out to study the effect of a barbiturate agent (barbamil) administered in a dose of 150 mg/kg of animal body weight on cerebral capillary circulation at different terms of ischemia (1, 3 hours, 1, 3, 7, 14 days). The findings obtained during follow-up point to a beneficial effect of the barbiturate on the structures of the capillary wall (endotheliocytes, pericytes, basal membrane). Furthermore, the drug appears to maintain the capillary lumen and the normal level of capillary permeability, which contributes to the improvement of microcirculation in ischemia. The paper also describes some ultrastructural mechanisms of the decrease and stabilization of the cerebral capillary blood flow under the barbiturate impact due to endothelial synapses blockade, inhibition of vasoconstrictive mechanisms and stabilization of the membrane structures of the capillary network.

Amobarbital↗
PubMedDate not supplied

Effect of octanoate on blood-brain barrier permeability using L-dopa as a marker.

Short-chain fatty acid injection into animals produces coma, seizures, and hyperventilation. One mechanism of coma production may be through alterations in membrane permeability characteristics. The SPG histofluorescence technique was used to evaluate changes in blood-brain barrier permeability to injected L-dopa in rats after intraperitoneal injections of the short-chain fatty acid, sodium octanoate. Diffusion of intravascular fluorescence was observed around brain capillaries in the octanoate-injected rats suggesting an alteration in capillary permeability to L-dopa. Diffusion of fluorescence around neuronal cell bodies and brain fiber tracts was also seen after treatment with octanoate. These findings suggest that octanoate may also alter neuronal membrane function.

Animals↗
PubMed1977

Absence of restricted diffusion in adipose tissue capillaries.

Capillary permeability in adipose tissue for 57Co-cyanocobalamin (57Co-B12) was determined by the single injection, external registration method. The capillary diffusion capacity, CDC, (the permeability-surface area product, PS) was 1.1 ml/100 g-min at a capillary extraction of 0.21 and a plasma flow of 6.7 ml/100 g-min. Results were compared to 51Cr-EDTA data from a previous study with similar method and preparation. As CDC(51Cr-EDTA)/CDC(57Co-B12) was 1.81 and as D(51Cr-EDTA)/D(57Co-B12), the ratio between the free diffusion coefficients in water at 37 degrees C, was 1.79, it is concluded that restricted diffusion does not occur in cutaneous tissue for 57Co-B12 as compared to 51Cr-EDTA, i.e., 51Cr-EDTA and 57Co-B12 diffuse across the capillary membrane of adipose tissue at rates proportional to their respective free diffusion coefficients in water. The Pappenheimer equivalent pore radius estimate of 30 A and the Karnovsky interendothelial 40 A slit width are both defective in explaining the experimental data. The transendothelial channel system of fused vesicles (Simionescu, Simionescu and Palade 1975) is a possible structural equivalent for the present findings. The results support the hypothesis that capillaries of continuous type exhibit similar permeation characteristics regardless of the tissue in which they are located.

Adipose Tissue↗
PubMed2006

Adipose-specific effect of rosiglitazone on vascular permeability and protein kinase C activation: novel mechanism for PPARgamma agonist's effects on edema and weight gain.

PPARgamma agonists, thiazolidinediones, cause fluid retention and edema due to unknown mechanisms. We characterized the effect of rosiglitazone (RSG), a thiazolidinedione, to induce vascular permeability, vascular endothelial growth factor (VEGF) expression, and protein kinase C (PKC) activation with edema and wt gain. In lean, fatty and diabetic Zucker rats, and endothelial insulin receptor knockout mice, RSG increased wt and vascular permeability, selectively in fat and retina, but not in heart or skeletal muscle. H2O content and wt of epididymal fat were increased by RSG and correlated to increases in capillary permeability in fat and body wt. RSG induced VEGF mRNA expression and PKC activation in fat and retina up to 2.5-fold. Ruboxistaurin, a PKCbeta isoform inhibitor, in the latter 2 wk of a 4-wk study, normalized vascular permeability in fat and decreased total wt gain, H2O content, and wt of fat vs. RSG alone but did not decrease VEGF expression, basal permeability, or food intake. Finally, RSG did not increase wt or vascular permeability in PKCbeta knockout vs. control mice. Thus, thiazolidinedione's effects on edema and wt are partially due to an adipose tissue-selective activation of PKC and vascular permeability that may be prevented by PKCbeta inhibition.

Adipose Tissue↗
PubMed1991

Effects of Escherichia coli endotoxin on structure and permeability of myocardial capillaries.

A study was carried out to investigate changes in myocardial capillaries induced by endotoxin, in order to clarify the pathogenesis of myocardial damage in endotoxemia. Wistar rats were injected intraperitoneally with 100 mg/kg Escherichia coli lipopolysaccharide and then sacrificed at 1, 2, 3,4, 5, 6, 8, and 24 h after injection. The myocardium was observed by electron microscopy with histochemistry using horseradish peroxidase and immunocytochemistry for Na+, K(+)-ATPase/TPase. The earliest evident endothelial alterations were swelling, increased numbers of pinocytotic vesicles, and formation of cytoplasmic projections. Interstitial edema and focal detachment of the endothelial cells from the basement membrane occurred with time. Vascular permeability was increased after endotoxin injection. Activity of Na+, K(+)-ATPase was reduced on the plasma membrane of the endothelial cells. It is concluded that endotoxin induces structural and enzymatic changes in the myocardial capillary endothelium and an increase of capillary permeability.

Animals↗