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PubMed1981

Assessment of alveolar-capillary membrane permeability of dogs by aerosolization.

We developed a method for measuring an index of alveolar-capillary membrane permeability (PI) by aerosolizing a mixture of 99mTc-diethylenetriaminepentaacetic acid (Tc-DTPA) and 125I-antipyrine (I-AP) and injecting 111In-DTPA (In-DTPA). The I-AP was used to compute the quantity of Tc-DTPA delivered and the In-DTPA the quantity of Tc-DTPA in the body. The PI was the ratio of the uptake of Tc-DTPA per minute to the amount deposited at the end of aerosolization. In 14 anesthetized dogs we measured the volume of distribution of I-AP (0.54 +/- 0.034 l/kg body wt) and/or showed that the volumes of distribution of Tc-DTPA and In-DTPA were similar. We measured PI in four groups of dogs: control (n = 5), oleic acid (n = 5), hydrochloric acid (n = 6), and high left atrial pressure (n = 5). The PI increased significantly in both groups with acid-induced increased permeability compared with the control and high left atrial pressure groups, which did not differ from each other. We conclude that the aerosolization method is suitable for differentiating increased from normal permeability.

Aerosols↗
PubMed1999

Reflection coefficient for albumin and capillary fluid permeability in cat calf muscle after traumatic injury.

Surgery and traumatic injury are often followed by tissue oedema and a low plasma albumin concentration, indicating leakage of fluid and proteins from the intravascular to the interstitial space. Transcapillary leakage can be referred to as an increase in capillary hydraulic conductance and/or a decrease in the reflection coefficient for plasma macromolecules. This study evaluates if time-dependent variations in the reflection coefficient for albumin and capillary hydraulic conductance can be confirmed experimentally following a surgical trauma using a blood perfused cat skeletal muscle in vivo preparation. The hydraulic conductance was estimated by the capillary filtration coefficient, and was used to evaluate variation in capillary fluid permeability. According to the Starling fluid equilibrium, the ratio between the reflection coefficients for albumin on two occasions can be calculated from the maximum osmotic absorption rates induced by a fixed intravenous bolus infusion of albumin (0.5 g kg(-1)) and from the capillary filtration coefficients. We found a decrease in the reflection coefficient of about 30% up to 10 h after the preparation. The capillary filtration coefficient showed no significant change over time, but decreased by 5-10% following the albumin infusion. We conclude that: (1) the reflection coefficient for albumin is reduced after a trauma, whereas the effects on the capillary fluid permeability are small, (2) albumin in plasma contributes to preserve normal capillary fluid permeability and, (3) the model seems to be useful for evaluation of relative variations in the reflection coefficient for albumin.

Albumins↗
PubMed1984

Effect of exogenous adenosine on resistance, capillary permeability-surface area and flow in ischemic canine myocardium.

The effects of adenosine on capillary-tissue exchange have not been evaluated. Although adenosine is a known vasodilator, its effects on nutritive flow are unknown. We therefore measured the influence of adenosine on resistance and capillary exchange in normal and mildly ischemic myocardium in 11 anesthetized, heparinized dogs. Flow to the left anterior descending artery was measured and controlled through an extracorporeal shunt from the carotid artery. Capillary permeability-surface area for sucrose (PS) was determined using the multiple-tracer technique in which mixtures of isotopes were injected into the coronary arterial shunt. We found that in the normal myocardium, intracoronary infusion of adenosine at 8 +/- 2 (S.E.M.) micrograms/ml of plasma significantly lowered resistance and increased PS. In the ischemic myocardium, however, large doses of adenosine (200 +/- micrograms/ml of plasma) lowered resistance but failed to increase PS. We interpret these results to mean that in mild, flow-reduction ischemia, adenosine did not lead to a recovery of capillary surface area for exchange, but simply increased flow through capillaries which had already been functioning. Nutritional flow was not enhanced.

Adenosine↗
PubMed2007

Anti-inflammatory activity of bis(3-aryl-3-oxo-propyl)methylamine hydrochloride in rat.

In this study the effects of compound B1, bis(3-aryl-3-oxo-propyl)methylamine hydrochloride, and an anti-inflammatory drug, indomethacin, were tested by carrageenan-induced paw edema and cotton pellet granuloma tests, for effects on acute and chronic phases of inflammation, respectively. Their effects on vascular permeability were also determined by hyaluronidase-induced capillary permeability test. Anti-inflammatory activity of B1 was compared with indomethacin. B1 decreased the carrageenan-induced paw edema by 49%, 35%, and 47% at 50, 100, and 200 mg kg(-1) doses, respectively, while this decrease was 82% by indomethacin at 20 mg kg(-1) dose. Antiproliferative effects in cotton pellet test of B1 at 50 mg kg(-1) and indomethacin at 20 mg kg(-1) doses were 44% and 43%, respectively. Indomethacin but not B1 inhibited the hyaluronidase-induced increase in capillary permeability. Our results suggest that B1 inhibits both acute and chronic phases of inflammation probably by an effect not mediated by prevention of increased capillary permeability. Especially, its anti-inflammatory activity against chronic phase of inflammation was comparable with that of indomethacin. Further detailed studies are needed to clarify the mechanism(s) of action responsible for the anti-inflammatory activity of B1.

Animals↗
PubMed1996

Antihypertensive drugs and endothelial cell function.

Arterial hypertension is associated with increased capillary permeability, a possible contributor to the vascular remodeling process which could be involved in certain pathological conditions arising from elevated blood pressure. This study evaluated the effects of various antihypertensive drugs on capillary permeability in the normal rat, using Evan's blue dye (EB) as a marker of albumin extravasation. The results reveal that acute injection of certain diuretics (furosemide, indapamide, hydrochlorothiazide) increase while others (amiloride, cicletanine) decrease capillary permeability via stimulation of the cyclooxygenase pathway. 10 day gavage with indapamide, amiloride and cicletanine, as well as angiotensin-converting enzyme (ACE) inhibitor perindopril and calcium channel blockers nifedipine and verapamil decreases capillary permeability, whereas furosemide, hydrochlorothiazide, ACE inhibitor captopril and calcium channel blocker clentiazem do not modify or increase EB extravasation. Hence, selected antihypertensive agents reduce capillary permeability and could therefore have a supplemental protective vascular effect, in addition to their lowering arterial pressure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1977

Endotoxin-induced increased alveolar capillary membrane permeability.

In an attempt to define the effects of endotoxin on the permeability of the pulmonary alveolar capillary membrane (ACM) to a variety of substances [molecular weight (MW) varying from 60 to 69,000], we studied the movement of specific molecular species from the pulmonary capillary blood to the saline-filled "alveolus," employing an in vivo dog lung model. Following endotoxin injection (2-2.5 mg/kg) baseline T1/2 values (time, in minutes, for 50% equilibration of the specific solute between the blood and the saline-filled lung) decreased as follows (compared to baseline values): urea (MW 60) - 42.5 +/- 24 to 21.3 +/- 18; sucrose (MW 360) - 201 +/- 72 to 76 +/- 53; 3,000 MW dextran - 1,275 +/- 746 to 686 +/- 433; 10,400 MW dextran - 1,871 +/- 845 to 1,052 +/- 630 (all p less than 0.05). Neither 20,000 MW dextran nor albumin (MW 69,000) showed an increased permeability following endotoxin injection. Histamine analysis revealed a significant increase in all lung liquid samples post-endotoxin injection without a significant increase in blood histamine values. We conclude that, acutely (within 4 hr of injection), endotoxin causes an increase in permeability of the ACM for substances up to 10,400 MW. The role of histamine in this increased permeability remains controversial.

Animals↗
PubMed1995

[Antioxidant action of gabexate mesilate (Foy) in an experimental model of endotoxic shock].

BACKGROUND: Circulatory shock, especially endotoxin shock, is characterized by the release of a large number of mediators, among which proteases play a key role. The production of oxygen free radicals into the extracellular space and the increase of capillary permeability is one of the most important consequences of that phenomenon. In order to evaluate the efficacy of gabexate mesilate (Foy) in preventing such increase of microvascular permeability, an experimental model of endotoxin shock was used. MATERIALS AND METHODS: Experiments were performed on the mesocecum of male Wistars rats, fluorescent labeled bovine albumine was injected intrarterially to evaluate the capillary permeability and the mesocecum microcirculation was observed by fluorescent light. The control group received saline i.v.; the II group received a DL 100 of E. coli endotoxin (DIFCO 0111: B4); the III and the IV group received a continuous infusion or topical application of gabexate mesilate respectively, before the administration of endotoxin. To evaluate capillary permeability and to quantify the degree of extravasion by counting the number of leaky sites, fluorescent labelled bovine albumin was injected i.v. and mesocecum was observed with fluorescent microscopy for 2 hours. RESULTS AND CONCLUSIONS: Capillary permeability did not increase in control rats; it largely increased in rats receiving endotoxin i.v. but it did not almost increased in rats receiving gabexate mesilate (Foy) that prevents the increase of capillary permeability that was observed in the group treated with endotoxin alone.

Animals↗
PubMed2006

Dynamic contrast-enhanced MRI quantification of synovium microcirculation in experimental arthritis.

OBJECTIVE: Our objective was to analyze MRI contrast-enhancement patterns in arthritic and nonarthritic knees and the relationship of those patterns with clinical, laboratory, and histologic synovium markers. MATERIALS AND METHODS: Dynamic contrast-enhanced MRI was performed in nine arthritic and three nonarthritic knees of juvenile rabbits. A two-compartment pharmacokinetic model of signal intensity-time data was implemented to generate parametric maps of signal slope, maximal percentage of signal change, capillary permeability, leakage space volume, and time-to-peak. MRI values were compared with clinical, laboratory, and histologic markers for evaluation of synovial changes during the progression of arthritis. RESULTS: Parametric maps of capillary permeability and signal slope depicted significant differences between arthritic and nonarthritic knees. Arthritic knees showed increased capillary permeability (p = 0.006) and signal slope (p = 0.01) with time after onset of disease as opposed to nonarthritic knees (permeability, p = 0.65; slope, p = 0.56). Significant correlations were found between temporal changes in capillary permeability (p = 0.002), signal slope (p = 0.003), and serum concentrations of amyloid A. No relationship was noted between any MRI parameters and histologic scores. The discriminative power of MRI indexes varied according to the stage of arthritis: time-to-peak was most accurate for differentiation of presence versus absence of arthritis in early arthritis (day 1, p = 0.0002), and signal slope was most accurate in midterm arthritis (day 14, p = 0.001). CONCLUSION: In vivo capillary permeability and signal slope have distinctive dynamic MRI properties. The accuracy of MRI parameters for diagnostic evaluation of experimental arthritis differs according to the stage of disease.

Animals↗
PubMed1983

Effects of methylprednisolone on peritumoral brain edema. A quantitative autoradiographic study.

Peritumoral brain edema was produced by intracerebral transplantation of Walker 256 tumor in rats. Local cerebral blood flow (LCBF), local cerebral glucose utilization (LCGU), and capillary permeability were studied in untreated and methylprednisolone-treated rats by quantitative autoradiography. In the untreated group, LCBF and LCGU were widely depressed in the cortex and deep structures of the hemisphere ipsilateral to the tumor. In the methylprednisolone-treated animals, LCBF and LCGU were significantly better than in the untreated animals. Capillary permeability was highly increased in the viable part of the tumor in the untreated animals. In the methylprednisolone-treated group, capillary permeability of the tumor was significantly lower than that in the untreated group. These results may suggest that increase in capillary permeability of the tumor is the major source for edema fluid production, and that methylprednisolone improves brain edema by decreasing capillary permeability of the tumor. Decrease in edema fluid formation may result in restoration of blood flow and glucose metabolism in the adjacent brain tissue, and may improve clinical symptoms and signs.

Animals↗
PubMed1979

Alveolar-capillary membrane permeability. Correlation with functional, radiographic, and postmortem changes after fluid aspiration.

An index of permeability of the alveolar-capillary membrane was derived from the relative extraction from the lung into arterial blood of 2 tracers, 125I-antipyrine and 51Cr-ethylenediaminetetraacetate. The effect on this index of aspirating 2 ml of isotonic saline, distilled water, or 10(-1) M hydrochloric acid per kg of body weight was studied in 3 groups of rabbits. The severity and time course of changes in the permeability index were correlated with changes in lung mechanics, gas exchange, serial chest roentgenograms, ratio of extravascular lung water to dry weight, and histologic findings. Aspiration of saline produced no change in the permeability index; aspiration of water produced a large mean +/- SEM increase in the index, from a baseline of 0.025 +/- 0.002 to 1,050 +/- 0.054 (P less than 0.001), but this value returned to baseline 15 min later. After hydrochloric acid, the permeability index increased from a baseline of 0.027 +/- 0.003 to 1.068 +/- 0.098 (P less than 0.005), with no evidence of resolution after 60 min. Changes in lung mechanics, gas exchange, and roentgenograms were smallest after aspiration of distilled water and greatest after aspiration of hydrochloric acid. The functional changes after aspiration of water and saline recovered at a rate proportional to the known clearance rates of these liquids from the lung. The changes after hydrochloric acid either showed no tendency toward recovery or, in the case of the roentgenograms, worsened with time. There were no detectable histologic abnormalities or an increase in the ratio of extravascular lung water to dry weight after aspiration of water or saline, but there were extensive histologic abnormalities and a 70 per cent increase in lung water after acid. The increase in the permeability index after aspiration of water was too transient to exert a deleterious effect. In contrast, the persistence of the increase in the permeability index after hydrochloric acid was associated with persistent functional changes attributable to the considerable increase in lung water.

Animals↗
PubMed1998

Desflurane increases pulmonary alveolar-capillary membrane permeability after aortic occlusion-reperfusion in rabbits: evidence of oxidant-mediated lung injury.

BACKGROUND: Pulmonary injury occurs after vascular surgery, with xanthine oxidase (an oxidant generator) released from reperfusing liver and intestines mediating a significant component of this injury. Because halogenated anesthetics have been observed to enhance oxidant-mediated injury in vitro, the authors hypothesized that desflurane would increase alveolar-capillary membrane permeability mediated by circulating xanthine oxidase after thoracic occlusion and reperfusion. METHODS: Rabbits were assigned to one of five groups: aorta occlusion groups administered desflurane (n=14), desflurane and tungstate (xanthine oxidase inactivator, n=12), fentanyl plus droperidol (n=13), and two sham-operated groups (desflurane, n=7 and fentanyl plus droperidol, n=7). Aortic occlusion was maintained for 45 min with a balloon catheter, followed by 3 h of reperfusion. Alveolar-capillary membrane permeability was assessed by measurement of bronchoalveolar lavage fluid protein. Xanthine oxidase activity was determined in plasma and lung tissue. Ascorbic acid content (an antioxidant) was determined in lung tissue. RESULTS: Desflurane was associated with significantly increased alveolar-capillary membrane permeability after aortic occlusion-reperfusion when compared with the fentanyl plus droperidol anesthesia or sham-operated groups (P < 0.05). Inactivation of xanthine oxidase abrogated the alveolar-capillary membrane compromise associated with desflurane. Although significantly greater than for sham-operated animals, plasma xanthine oxidase activities released after aortic occlusion-reperfusion were not different between the two anesthetics. There were no anesthetic-associated differences in lung tissue xanthine oxidase activity. However, desflurane anesthesia resulted in a significant reduction in lung ascorbic acid after aortic occlusion-reperfusion compared with the sham-operated animals. CONCLUSIONS: Desflurane anesthesia increased xanthine oxidase-dependent alveolar-capillary membrane compromise after aortic occlusion-reperfusion in concert with depletion of a key tissue antioxidant.

Anesthetics, Inhalation↗
PubMed1981

[Changes of blood-brain barrier in the ethylnitrosourea induced rat glioma (author's transl)].

Capillary permeability of rat brains bearing ethylnitrosourea induced rat glioma was measured with quantitative autoradiography. In the small tumors (less than 2mm in diameter), no changes in capillary permeability was noted. When tumors became larger and neovascularization of the tumor occurred, increase in capillary permeability was evident. This change was more prominent in the center of the tumor than in the periphery. In the large tumors, the capillary permeability was markedly increases, and the value was similar to that in the choroid plexus. This indicates that blood-brain barrier(BBB) completely disappeared in the large tumors. This BBB change may be the main cause of tumor induced brain edema. The data also provide the information about pharmacokinetics of water soluble drugs in the brain tumors.

Animals↗
PubMed2002

Water permeability of capillaries in the subfornical organ of rats determined by Gd-DTPA(2-) enhanced 1H magnetic resonance imaging.

The water permeability of capillaries in the subfornical organ (SFO) of rat was measured by a (1)H nuclear magnetic resonance method in combination with a venous injection of a relaxation reagent, gadolinium-diethylene triamine-N,N,N',N",N"-pentaacetic acid (Gd-DTPA(2-)), which could not pass through the blood-brain barrier (BBB). Judging from results of Gd-DTPA(2-) dose dependency in the intact brain and the BBB-permeabilized brain, Gd-DTPA(2-) could not have leaked out from the capillaries in the cortex, thalamus or SFO, but it could have been extravasated in the posterior lobe of the pituitary gland. The longitudinal (T(1)) relaxation time of water in the SFO region was measured by inversion-recovery magnetic resonance imaging at 4.7 T. The T(1) relaxation rates (1/T(1)) before and after Gd-DTPA(2-) infusion were 0.70 +/- 0.02 s(-1) (mean +/- S.E.M., n = 9) and 1.53 +/- 0.11 s(-1) (n = 9), respectively. The rate constant for water influx to the capillaries was estimated to be 0.84 +/- 0.11 s(-1) (n = 9) which corresponds with a diffusive membrane permeability (P(d)) of 3.7 x 10(-3) cm s(-1). Compared with values found in the literature available on this subject, this P(d) value for the capillaries in the SFO was the same order of magnitude as that for transmembrane permeability of water for the vasa recta, and it may be 10-100 times larger than that of the blood-brain barrier in the cortex. Areas of the cortex and thalamus showed minimal changes in the T(1) relaxation rate (ca 0.09 s(-1)), but these values were not statistically significant and they corresponded to P(d) values much smaller than those found in the SFO. From these results, we conclude that the capillaries in the SFO have one of the highest water permeability values among all of the capillaries in the brain. It is also suggested that this magnetic resonance imaging, based on T(1) relaxation rate, is a useful method to detect local water permeability in situ.

Animals↗
PubMed1989

Noninvasive measurement of microvascular permeability to small solutes.

Quantification of microvascular permeability to diffusible hydrophilic solutes has received little attention in a clinical setting, probably because of a lack of noninvasive techniques. We describe a gamma camera technique which measures the clearance of 99Tcm-DTPA from the intravascular to extravascular space in extra-renal regions of interest over the lumbar region, the tissues within which being predominantly skin and muscle. This regional clearance (PSr), normalized to 100 ml of tissue, represents the permeability-capillary surface area (PS) product, a classical concept for describing solute transfer across the capillary. We found a mean value in 14 patients with normal renal function of 1.0 (S.D. 0.2) ml/min/100 ml of tissue, which is broadly similar to values anticipated from published values of 51Cr-EDTA extraction fraction (in a single pass) in human skeletal muscle and resting muscle plasma flow. The technique also generates the plasma volume (tPV) within this subrenal tissue, which we found to be 5.0 (2.0) ml/100 ml. In an attempt to reproduce an index of extraction fraction we also calculated the ratio PSr:tPV and this was 0.23 (0.08) min-1. This approach could prove useful in a variety of clinical settings.

Capillary Permeability↗