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PubMed1991

Myocardial capillary permeability for small hydrophilic indicators during normal physiological conditions and after ischemia and reperfusion.

Myocardial capillary permeability for small hydrophilic solutes (51Cr-EDTA or 99mTc-DTPA) has been measured using intracoronary indicator bolus injection and external radioactivity registration (the single injection, residue detection method). The method is based on kinetic separation of the injected indicator molecules in an extracted and a transmitted fraction of molecules. In open chest dog hearts measurements performed during normal physiological conditions gave mean capillary extraction values of 43.5-47.5% and the corresponding calculated PdS values were 47.1 - 57.5 ml.(100g.min)-1. From these PdS values Pd values between 1.57.10(-5) and 1.92.10(-5) cm.s-1 were calculated, in accordance with values obtained by other methods. Similar data have been obtained in myocardium of patients undergoing coronary angiography. Oxygen derived free radicals seems to participate in reperfusion injury including microvascular alterations. In open chest dogs transitory increases in capillary extraction fraction and PdS for small hydrophilic solutes were seen following 20 minutes of regional myocardial ischemia and reperfusion. This response could be inhibited by treatment directed against superoxide radicals.

Animals↗
PubMed1985

Effect of hypoxia on feline intestinal capillary permeability.

The multiple-indicator dilution technique was used to investigate the permeability characteristics of capillaries in the cat small intestine during hypoxia. Reducing the arterial oxygen tension from 108 to 35 mmHg for 10 min increased the calculated equivalent pore radius of intestinal capillaries from 59 to 67 A. This effect was sustained for at least 15 min after the hypoxic episode. Hypoxia did not alter intestinal lymphatic protein clearance. Thus, the dimensions of the large pores did not change. This study demonstrates that 10 min of severe hypoxia increases vascular permeability in the small intestine and that this change occurs only in the small pores and is sustained, at least briefly, after restoration of normoxia. Hypoxia does not significantly change the permeability to macromolecules.

Animals↗
PubMed1986

Capillary permeability in rat hindquarters as determined by estimations of capillary reflection coefficients.

Osmotic reflection coefficients (sigma) for a variety of solutes ranging from NaCl to albumin were determined in perfused maximally vasodilated rat hindquarters employing the osmotic transient method (Vargas & Johnson 1964). Measurements were performed at high flows and using short tubings with small volumes. Intracapillary solute concentrations of the osmotic transients were measured or estimated for solutes of the size of inulin or smaller. The PS for Cr-EDTA and cyanocobalamine were determined repeatedly in half of the experiments using an on-line modification of the single injection (indicator diffusion) method (Rippe & Stage 1978) and capillary filtration coefficients (CFC or LpS) were followed in all experiments. The capillary osmotic reflection coefficient was determined to 0.05 for NaCl, to 0.08 for sucrose, to 0.39 for inulin, to 0.57 for myoglobin and to 0.87 for albumin. These reflection coefficients were compatible with a 'small pore radius' of approximately 40 A (slit width (w) of approximately 50 A) according to modern hydrodynamic theories for the reflection coefficient and the parallel transcapillary pathway hypothesis. The best fit of the osmotic transient data to current theories for the reflection coefficient occurred if the major portion (86-87%) of the hydraulic conductivity (Lp) was accounted for by this paracellular 'small pore' (slit) pathway and if 3.0-4.1% of Lp could be ascribed to a transcellular pathway (sigma approximately I) while the remaining fraction (10%) of Lp was accounted for by a non-selective paracellular pathway (sigma approximately o); that is, by 'large pores'.

Animals↗
PubMed1991

[Microcirculation and capillary permeability during hemodialysis in patients with renal insufficiency].

Time course changes in microcirculation (MC) and capillary permeability (CP) were investigated in 191 patients with acute renal failure (ARF) and 45 patients with terminal chronic renal failure (CRF). Similar in type MC and CP disturbances were found in all CRF and oligoanuria ARF patients. These were more pronounced in CRF sufferers depending in degree on the disease severity. Knizeli's phenomenon ranged from 2.2.KII to 3.3.KIII. The total conjunctival index reached 22.99-25.20 in CRF and 19.4 in ARF. Unlike ARF patients, those with CRF had no positive trend in MC and CP. A transient change for the better came after hemodialysis and was seen in occasional patients. It is suggested that no response to hemodialysis is indicative of CRF and ARF poor prognosis. The trend in MC can help in prognostication of CRF development in acute cases.

Acute Kidney Injury↗
PubMed1989

Capillary permeability of 99mTc-DTPA in canine myocardium determined by intracoronary bolus injection and residue detection.

Capillary permeability of 99mtechnetium-diethylenetriaminepenta-acetic acid (99mTc-DTPA; MW 485.0) and 51chromium-ethylenediaminetetra-acetate (51Cr-EDTA; MW 340.2) was studied in an in vivo canine heart preparation by the single injection, residue detection (SIRD) method. In experiments on open chest dogs (group A) these indicators were administered separately as bolus injections into a cannulated diagonal branch of the left anterior descending coronary artery (LAD) and the curve of the response function was recorded by external activity registration. In further experiments on closed and open chest dogs (group B) 99mTc-DTPA was injected via a coronary angiography catheter into the ostium of the left coronary artery and the response curve was obtained by external registration. Regional myocardial perfusion coefficients were determined by the local 133xenon washout technique and from kinetic analysis of SIRD experiments. Plasma perfusion coefficients calculated by kinetic analysis of response curves from 99mTc-DTPA SIRD experiments (group A) were on average 98 v 102 ml.min-1.100 g-1 in 51Cr-EDTA experiments, in good agreement with the average plasma flow rate of 92 ml.min-1.100 g-1 determined by local 133Xe washout technique. Mean values of the extraction fractions (E) were 0.463 and 0.475 for 99mTc-DTPA and 51Cr-EDTA, and the permeability-surface area products (PdS) were 52.8 and 57.5 ml.min-1.100 g-1 respectively. At the conventional capillary surface area estimate of 500 cm2.g-1 the permeability coefficient (Pd) for 99mTc-DTPA was 1.76.10(-5) cm.s-1 and for 51Cr-EDTA 1.92.10(-5) cm.s-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[Method of the determination of skin capillary permeability].

A new noninvasive impedance method has been proposed to determine the permeability of skin capillaries, which involves measurement of the electric resistance of a skin area before and after exposure to negative pressure. There is a convergence of clinical data and simulation findings. The changes in the permeability coefficient were studied in different periods after recovery of adequate blood supply in the diseased limb. The investigation has allowed the developed permeability coefficient to be included into the algorithm of diagnosing and treating patients with arterial diseases.

Algorithms↗
PubMed1980

The effect of dibenzazepines (tricyclic antidepressants) on cerebral capillary permeability in the rat in vivo.

The degree of equilibration of [3H]water across the cerebral capillary was evaluated by measuring its cerebral extraction fraction (Ew) by using a dual label radioactive tracer technique. All tricyclic antidepressants (125 mumol/kg i.p. at 5 min) increased Ew as compared to base line. The rank order of the drugs in producing this response was doxepin greater than amitriptyline greater than imipramine greater than nortriptyline greater than desmethylimipramine greater than protriptyline. The effect of amitriptyline, the prototype tricyclic for this study, was rapid in onset (maximal effect within 5 min), reversible (duration 15 min), dose-dependent and generalized throughout the brain. Amitriptyline also induced a marked increase in the cerebral extraction fraction of [3H]ethanol. A difference in the time course of the drug effect on these two tracers indicated that the elevation in E was due to the increase in cerebral capillary permeability to both polar and lipid soluble substances. This work demonstrates that tricyclic antidepressants have important central effects on non-neuronal tissue.

Amitriptyline↗
PubMed1971

Dextrans and glycogens as particulate tracers for studying capillary permeability.

Commercially available glycogens and dextrans can be used as biological particulate tracers in work on capillary permeability. These polysaccharides are well tolerated in intravenous injection and induce no vascular leakage when applied topically (cremaster test) in mice and in Wistar-Furth rats. The particles stain adequately with lead after aldehyde-OsO(4) fixation in phosphate buffer and provide a relatively wide set of probes ( approximately 45 A-300 A) for work on the large and small pore systems.

Animals↗
PubMed1994

Effect of perfusate pH on reduction of quinidine capillary permeability by albumin in isolated perfused rat heart.

It has been suggested that albumin reduces quinidine capillary permeability (PS) in the single-pass perfused heart preparation by reducing paracellular transport of quinidine ions. Using this preparation, we examined the effect of albumin (0.1 per cent) on quinidine PS at perfusate pH's of 7.1 and 7.9 during uptake of quinidine (19 microM) and also during washout of the drug using a randomized design. Quinidine PS was approximately 16 ml/min/g heart at pH 7.9 and was not altered by the presence of albumin in perfusate. At pH 7.1, in the absence of albumin, quinidine PS was also 16 ml/min/g, but in the presence of albumin (0.1 per cent) PS was reduced significantly to approximately 5 ml/min/g (P < 0.001). In the absence of albumin PS was the same at pH 7.1 and 7.9 in spite of a greater degree of ionisation of quinidine at pH 7.1. This suggests that there is significant uptake of ionised quinidine at pH 7.1. The greater effect of albumin on PS at pH 7.1 supports the hypothesis that albumin reduces paracellular transport of quinidine ions.

Animals↗
PubMed1992

Effects of exogenous oxygen derived free radicals on myocardial capillary permeability, vascular tone, and incidence of ventricular arrhythmias in the canine heart.

OBJECTIVE: The aim was to examine the effects of exogenous oxygen derived free radicals on myocardial capillary permeability for a small hydrophilic indicator, postischaemic vascular tone, and the occurrence of arrhythmias in the canine heart in vivo. METHODS: Free radicals were generated by simultaneous intracoronary infusion of hypoxanthine and xanthine oxidase into normally perfused myocardium, and at reperfusion following five minutes of coronary occlusion, respectively, in 20 anaesthetised open chest dogs. Myocardial capillary extraction for 99mTc-DTPA, plasma flow rate, and the interstitial washout rate constant were measured by the single injection, residue detection method, and the capillary permeability-surface area product (PS) was calculated. The maximum plasma flow during reactive hyperaemia was measured by the local 133Xe washout method. RESULTS: Hypoxanthine and xanthine oxidase infusion into normally perfused myocardium induced a 15% decrease in capillary extraction (p = 0.05), a 24% decrease in PS (p < 0.01), and a 23% decrease in the interstitial washout rate constant (NS) two minutes after the end of the infusion. When hypoxanthine and xanthine oxidase were infused into postischaemic myocardium, 86% of animals developed sustained ventricular arrhythmias, in contrast to none in control experiments (p < 0.05). The maximum plasma flow was 363% of preocclusive values in control experiments v 268% in hypoxanthine + xanthine oxidase experiments (p < 0.05). CONCLUSIONS: In normally perfused hearts, intracoronary infusion of hypoxanthine and xanthine oxidase induce a decreased capillary extraction, suggesting a reduced capillary surface area. In postischaemic myocardium these substances cause a decreased vasodilatation in the initial phase of reactive hyperaemia, and induce ventricular arrhythmias.

Animals↗
PubMed1987

Renal capillary permeability and intravascular red cell aggregation after ischaemia. I. Effects of xanthine oxidase activity.

The macromolecular permeability of renal capillaries and the intravascular red cell aggregation resulting from 45 min of warm ischaemia were investigated. The effects of the xanthine oxidase inhibitor Allopurinol on these factors and also on the post-ischaemic nephron function were also studied. Following ischaemia there was a more than 10-fold increase in the transport from plasma to renal hilar lymph both of plasma proteins and of two isomers of lactate dehydrogenase (LDH)-the nearly neutral LDH-M4 and the negatively charged LDH-H4. The ischaemia also resulted in massive intravascular red cell aggregation, especially in the renal medulla. Through reduction of plasma xanthine oxidase activity from 13.1 +/- 1.1 microU microliter-1 (mean +/- SEM) to essentially zero by Allopurinol, the capillary leakiness was substantially diminished with almost complete normalization after 120 min. At the same time the relative volume of trapped red cells was reduced; in the inner stripe of the outer medulla, for example, it decreased from 11.3 +/- 1.7% in untreated animals to 4.0 +/- 1.1% after treatment with 20 mg of Allopurinol given intravenously 3 h before the ischaemia. Oral feeding with 4 mg of Allopurinol day-1 for one week gave essentially the same result. The net driving force for filtration after treatment with this drug was thus 19 mmHg, as against 26 mmHg in the normal kidney and the resulting SNGFR was half the normal. The total filtration rate was proportionally more reduced to less than 1/3 of the normal. Tubular obstruction was still present but was not as severe as in untreated kidneys (Karlberg et al., 1982b) where the tubular fluid flow and thereby the filtration are essentially zero. It is suggested that oxygen free radicals increased the macromolecular permeability and the adhesiveness of white blood cells and that these two factors combined underlie the aggregation of red blood cells in the medullary vasa recta with consequent persistence of medullary ischaemia.

Allopurinol↗
PubMed2006

ACE gene insertion/deletion polymorphism modulates capillary permeability in hypertension.

A D/D (deletion/deletion) polymorphism within the ACE (angiotensin 1-converting enzyme) gene increases the risk of microalbuminuria, a predictor of atherosclerotic vascular disease, in essential hypertension. It is unknown, however, whether this genetic profile is accompanied by disturbed macromolecular permeability of systemic capillary endothelium, possibly in the context of generalized endothelial dysfunction. In the present study, the ACE gene polymorphism was determined by PCR in 79 never-treated uncomplicated hypertensive men and 16 normotensive men as controls. Evaluation variables were TERalb (transcapillary escape rate of albumin; the 1-h decline rate of intravenous (125)I-albumin, a measure of integrity of systemic capillary endothelium), albuminuria and forearm vasodilation to intra-arterial acetylcholine, an index of NO (nitric oxide)-mediated vasomotion, in addition to a series of sensitive parameters of albumin permeation (blood pressure, metabolic status and smoking habits). Analyses were done by comparing D/D homozygotes with grouped I/D (insertion/deletion) and I/I (insertion/insertion) subjects. TERalb was higher in D/D hypertensives, who had higher albuminuria, more frequent microalbuminuria and comparable forearm responsiveness to intra-arterial acetylcholine. Fasting glucose and insulin, insulin sensitivity, 24-h blood pressure, smoking habits and metabolic parameters did not differ between the two groups. TERalb and urine albumin values were positively associated in the hypertensive subjects. In conclusion, ACE D/D homozygosis, independently of several confounding factors, associates with higher TERalb in men with essential hypertension. This may reflect noxious genetic influences on systemic vascular permeability, a critical control mechanism for atherogenesis in the absence of grossly impaired NO-mediated arteriolar responsiveness. The parallel behaviour of TERalb and albuminuria suggests some shared genetically mediated determinant of renal and systemic microvascular abnormalities in hypertension.

Albuminuria↗
PubMed1993

Hypoxia induced disruption of the cardiac endothelial glycocalyx: implications for capillary permeability.

OBJECTIVE: The aim was to determine the effect of hypoxia on the ultrastructure of the endothelial glycocalyx of cardiac capillaries. METHODS: Isolated rat hearts were perfused with oxygenated or hypoxic Krebs solution for 30 min after equilibration with oxygenated medium. They were then perfused with a cationic marker (ruthenium red, lanthanum nitrate, or cationised ferritin) to delineate the cardiac endothelial glycocalyx in the electron microscope. With ruthenium red and lanthanum, perfusions were carried out both in the presence and absence of bovine serum albumin. Ferritin perfused hearts were used to quantify changes in the glycocalyx as a result of hypoxia and to measure the cross sectional area of the endothelial cells. RESULTS: In all the hearts perfused with well oxygenated solution, all three markers showed an even, electron dense layer on the luminal surface of the capillaries. With ruthenium red and lanthanum (but not with ferritin), the marker was occasionally observed throughout the length of the interendothelial clefts and on the albuminal surface. After 30 min hypoxic perfusion, both ruthenium red and lanthanum showed disruption and irregular clumping of the glycocalyx, with or without albumin. Ferritin, however, showed a sparse and uneven layer. Measurements of endothelial cell area showed that some cells from hypoxic hearts were swollen when compared with controls. Measurements of the percentage of luminal membrane covered by ferritin molecules showed a significant loss of glycocalyx in hypoxic hearts. There was, however, no correlation between loss of glycocalyx and endothelial cell swelling. CONCLUSIONS: The endothelial cell glycocalyx of continuous capillaries is sensitive to changes in PO2. The disruption of this surface coat may explain the reported increase in capillary permeability in hypoxia.

Animals↗
PubMed2005

[Capillary permeability and macromolecular exchange with special reference to structure of microvascular walls].

This paper reviews current concepts of capillary permeability of lipophilic and hydrophilic solutes, and macromolecular exchange across the microcirculation with special reference to structure of microvascular walls. Lipophilic and hydrophilic solutes must be differentiated because the barriers encountered by these classes of substances in the capillary walls are very different. Most hydrophilic solutes are mainly restricted to the paracellular pathway, whereas lipophilic solutes use the cellular pathway. Toward the end of the last century, Starling proposed that fluid flow through capillary walls is passive. He suggested that the energy for transcapillary fluid flow lay in the differences in hydrostatic and osmotic pressures between the circulating plasma and the tissues. It has been established that most proteins present in plasma cross capillary and venular walls, diffuse through the tissues, and return to the plasma via the lymphatic system. Thus both small and large pores are necessary to describe the movement of large molecules across the capillary and venular walls.

Animals↗