Regional variations of increased permeability of skin capillaries induced by a histamine liberator and their relation to the histamine content of the skin.
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Ultrastructural aspects of capillary function in irradiated bowel. An experimental study in the cat.
Irradiated small intestine of the cat has decreased capillary function measured as capillary filtration. This decrease may be due to changes in capillary permeability or decreased capillary area. An electron microscopic study was carried out to examine whether there were any ultrastructural changes consistent with impaired permeability. Cat ileum was irradiated with doses from 10 to 25 Gy and examined 4 days, 1 month, and 4 months after irradiation. In the acute phase (4 days) degenerative endothelial changes were seen and increased with dose. Congestion and microthrombi were also observed. One month after irradiation endothelial changes were still seen after 20 and 25 Gy, and an aggregation of fibrous matter adjacent to the capillary wall was prominent. The endothelial changes were subtle after 4 months, but the pericapillary and stromal fibrosis increased, and an increasing number of collagen fibrils appeared. Micropores disappeared after 20 and 25 Gy but returned later. Pinocytic vesicles were observed after all doses and intervals. The initial decrease in capillary filtration coefficient after irradiation may partly be due to permeability changes caused by endothelial degeneration, whereas the late decrease parallels the increasing pericapillary fibrosis.
Animals↗
Pulmonary edema and pleural effusion in norepinephrine-stimulated rats--hemodynamic or inflammatory effect?
Stimulation with norepinephrine (NE) leads to pulmonary edema and pleural effusion in rats. These pulmonary fluid shifts may result from pulmonary congestion due to the hemodynamic effects of NE and/or inflammation with an increase in vascular permeability. The contribution of these two factors were investigated in the present study. Female Sprague-Dawley rats received continuous i.v. NE infusion (0.1 mg/kg/h) over time intervals between 90 min and 72 h. After heart catheterization, pleural fluid (PF) and lung tissue were obtained. In some of the animals, a bronchoalveolar lavage (BAL) was performed. Pulmonary edema and inflammation were shown histologically. We determined the expression of interleukin (IL)-6 as one of the most potent acute-phase protein mediators in serum, PF and BAL supernatant fluid (BALF) using ELISA as well as in the lung tissue using Western blotting. Total protein concentration in BALF and PF served as indicators of increased capillary permeability. Pulmonary edema and pleural effusion appeared coincidentally with an increase in total peripheral resistance (TPR) after 6 h of NE infusion. PF reached a maximum between 8 and 16 h (2.2 +/- 0.3 ml, controls < 0.5 ml) and disappeared within 48 h. Activation of IL-6 in the fluids was observed after 8 h of NE stimulation. In the lung tissue it started after 12 h and reached 330% of the control value after 48 h. Pulmonary inflammation was documented histologically. It was accompanied by increased protein concentration in BALF after 24 h of NE treatment. Hemodynamic effects of NE are the main causative factors in the initial phase of the pulmonary fluid shifts. Additionally, NE leads to an activation of cytokines such as IL-6 and to inflammation and to an increase in capillary permeability. However, inflammation and increased capillary permeability occurred later than pulmonary edema and pleural effusion. Hence, we conclude that they are secondary factors which may contribute to maintain the fluid shifts over a longer period of time.
Animals↗
Action of gold thioglucose on pericapillary structures in the ventromedial hypothalamus.
The administration of GTG to mice leads to death of all structures in a circumscribed area of the VMH as a result of loss of blood circulation. The loss of circulation is due to damage by GTG of neural processes adjacent to some of the capillaries in this area; damage to these processes leads to abnormal capillary permeability. Pericapillary damage occurs under conditions where capillary damage and consequent necrosis are prevented. Abnormal capillary permeability appears to follow release of a vasoactive substance from the damaged neural processes. Damage to the pericapillary neural processes by GTG is insulin-dependent and is counteracted by glucocorticoids.
Animals↗
[Drug treatments of chronic venous insufficiency: pharmaco-clinical evaluation].
There are many methods for the assessment of venotropic drugs. Clinical trials based on randomized comparison with placebo are essential. The different methodes used for the evaluation of the functional effects are chosen on the basis of their performance and pertinence for the study objectives. These include three aims which we feel are essential: increased venous tone, decreased capillary permeability and reversal of microcirculatory impairment. Calf plethysmography is highly adapted for the evaluation of venous tone. The mercury gauge works well, but the future will tell if air plethysmography is more adapted here. For capillary permeability, fluoresceine angioscopy is without a doubt the most sensitive and specific method. Unfortunately many laboratories do not have this equipment. If it is not available, the suction cup test or the Landis isotope test may be used although these tests have their limits. For impaired microcirculation, the most interesting test is the laser-Doppler; the results are well correlated with the severity of the chronic venous insufficiency and return to normal after treatment. TcPO2 and capillaroscopic measurements are less sensitive, but are useful in severe cases. Other investigations may be important in individual cases depending on the impact of the medication under study. Drug-induced serum fibrinolytic activity can be measured by the euglobulin lysis time. A haemorheologic effect can be assessed with routine assays (Haematocrit, serum fibrinogen) and measured with tests of red cell deformability and erythrocyte agreggation capacity.
Blood Viscosity↗
Does "blastocyst estrogen" initiate implantation?
Fertilized eggs were incubated for 2 hours in a medium containing estradiol-17beta and then transferred into the uteri of day 5 pseudopregnant rats. These eggs, but not estrogen-free control eggs, induced a local increase in capillary permeability. We suggest that the blastocyst factor which induces the local increase in capillary permeability during early pregnancy is estrogen synthesized by the blastocyst.
Animals↗
Microvascular solute and water transport.
OBJECTIVE: This review evaluates (1) the regulation of water and solute transport across the endothelial barrier in terms of pore theory and the glycocalyx-junction-break model of capillary permeability; and (2) the mechanisms regulating permeability based on experiments using cultured endothelial cells and intact microvessels. CONCLUSIONS: The current form of the glycocalyx-junction-break model of capillary permeability describes the selectivity of the capillary wall (pore size) in terms of the space between the fibers of a quasi-periodic matrix on the endothelial cell surface, and the area for exchange (pore number) in terms of the length and frequency of breaks in the tight junction strands. An independent test of this model in a range of mammalian microvascular beds is new experimental evidence that the colloid osmotic pressure of plasma proteins is developed across the glycocalyx, not across the whole microvessel wall. We are beginning to understand that endothelial cells may change their phenotype in response to physical and chemical stresses. Such changes in phenotype may explain changes in the regulation of endothelial barrier function in intact microvessels that have previously been exposed to injury and differences in the regulation of contractile mechanisms between endothelial cells in vivo and in vitro.
Animals↗
Reduced total antioxidant capacity predicts ischaemia-reperfusion injury after femorodistal bypass.
BACKGROUND: Antioxidant defence systems are essential to protect the body from harmful free radicals released following ischaemia-reperfusion. The aim of this study was to examine the total antioxidant capacity (TAC) of patients with chronic critical leg ischaemia undergoing femorodistal bypass and to correlate this with lipid peroxidation, changes in capillary permeability and clinical outcome. METHODS: Twenty-five patients, 15 men and ten women of median age 71 (range 62-79) years, and 15 matched controls were studied. Blood was taken before operation and after reperfusion, with assays performed for malondialdehyde (a product of lipid peroxidation) and total antioxidant capacity. Changes in capillary permeability were measured by changes in the urinary albumin:creatinine ratio (ACR) following reperfusion of the ischaemic leg and expressed as a percentage increase from the preoperative value. Clinical outcome in terms of the systemic inflammatory response syndrome (SIRS) was recorded. RESULTS: Vascular patients who developed clinical evidence of a systemic inflammatory reaction following revascularization had a significantly reduced TAC compared with the controls (490 versus 860 mumol/l; P < 0.01, Mann-Whitney U test). These patients also demonstrated an increase in lipid peroxidation (0.5 versus 0.25 mumol/l, P < 0.05) and vascular permeability, as measured by the percentage increase in ACR (365 versus 130 per cent, P < 0.01). CONCLUSION: Vascular patients with a lower TAC developed increased capillary permeability as a result of ischaemia-reperfusion, which progressed to SIRS. TAC may provide a test to identify 'at risk' patients. It may be possible to augment their defence with exogenous antioxidants.
Aged↗
Abnormality of an index of alveolar-capillary barrier permeability associated with respiratory tract infection in the rat.
The study investigated the role of subclinical respiratory tract infection in producing an abnormality of lung function assessed by measuring an index of the permeability of the blood-gas barrier to 99mTcDTPA. Pasteurella pneumotropica was grown from throat swabs taken from 9 female rats age 10 weeks at the time of the experiment and housed under conventional husbandry conditions for 4 weeks previously. There was a significant association between the amount of bacteriological growth and an abnormality of the index of permeability. In contrast to this finding, there was no bacterial growth and no abnormality of function found in 12 female rats age 6 weeks, kept under strict barrier-maintained conditions. This finding emphasises the need for great care to be taken in the husbandry of animals used in scientific research.
Animals↗
Cerebrovascular permeability and cognition in the aging rat.
Regional cerebrovascular permeability-capillary surface area products (rPS) and brain vascular space (BVS) were measured in aging, conscious, unrestrained Sprague-Dawley rats. Three groups of animals were examined: young-mature (6 months), middle-aged (12-14 months), and old (24-26 months) rats. Complex maze learning had been previously characterized in these same animals. Maze learning declined with age. Brain vascular space did not differ significantly with age in any brain region. However, small, but significant age-dependent decreases in rPS (25-33%) were observed. These decreases occurred mainly in the old animals in the basal ganglia and parietal cortex, and in the middle-aged and old rats in the olfactory bulbs. Significant and unexpected positive average correlations between brain permeability-capillary surface area products (PS) and learning errors occurred primarily in young rats and were attributable mainly to changes in 5 of 14 brain regions; hypothalamus, hippocampus, parietal cortex, septal area and superior colliculus. The higher correlations between maze learning errors and PS in young animals may indicate dynamic regulation of this cerebrovascular parameter which is lessened with aging. Average correlations between PS and cerebral blood flow also were determined and found to be generally small and not significant for most brain regions and age groups.
Aging↗
Studies of recombinant streptococcal pyrogenic exotoxin B/cysteine protease (rSPE B/SCP) in the skin of guinea pigs & the release of histamine from cultured mast cells & basophilic leukocytes.
BACKGROUND & OBJECTIVES: Streptococcal pyrogenic exotoxin B/streptococcal cysteine protease (SPE B/SCP) is considered to be one of the virulence factors of Streptococcus pyogenes (S. pyogenes) which causes serious diseases such as severe invasive infections and streptococcal toxic shock syndrome (STSS). There are no reports on the histamine releasing activity of SPE B/SCP from mast cells, although several biological activities have been studied. It is not clear whether SPE B/SCP have the superantigenic activity. We studied whether SPE B/SCP plays as a pathogenic factor in streptococcal infections and STSS through a histamine releasing activity. METHODS: Human mast cells and basophils were generated from CD34 positive cells isolated from cord blood and cultured in the presence of rIL-6, stem cell factor and/or rIL-3. The capacity of increasing capillary permeability of recombinant SPE B/SCP (rSPE B/SCP) was studied by using the skin of guinea pigs. Mitogenic activity to human T-cells of rSPE B/SCP was studied by incorporation of (3)Hthymidine. The levels of histamine in the plasma of patients with STSS and controls were measured by ELISA kit. RESULTS: rSPE B/SCP induced increased capillary permeability in the skin of guinea pigs, but both SPE A and SPE C did not exhibit such activity. Histamine was released from cultured human mast cells stimulated with rSPE B/SCP. The rSPE B/SCP did not exhibit mitogenic activity to human T-cells. Three of the 7 patients with STSS showed higher levels of plasma histamine than those of normal subjects. INTERPRETATION & CONCLUSION: The results suggested that increased capillary permeability and histamine release from mast cells induced by rSPE B/SCP might be involved in STSS and/or streptococcal infection of skin and mucous membrane.
Animals↗
Quantitative evaluation of pinocytosis of capillaries of the stria vascularis under normal and experimental conditions.
In order to examine evidence of high activity of pinocytosis in capillaries of the stria vascularis, quantitative morphometry of pinocytotic vesicles was carried out ultrastructurally by the horseradish peroxidase (HRP) tracer method. In guinea pigs, there was a significant difference between the stria vascularis and spiral ligament in the number of vesicles per micron 2 (p less than 0.05) and labelled vesicles per micron 2 (p less than 0.001). In normotensive control rats, the number of labelled vesicles per micron 2 in capillaries of the stria vascularis was significantly greater (p less than 0.001) than that of the spiral ligament. Results of acute hypertensive and acute hypotensive experiments both indicated that enhanced permeable capillaries of the stria vascularis showed no significant increase in the number of pinocytotic vesicles per micron 2, but that they showed a more significant increase in the number of labelled vesicles per micron 2 than non-enhanced permeable capillaries of the stria vascularis (p less than 0.01) and capillaries of the spiral ligament (p less than 0.001). These findings provide ultrastructural confirmation of our previous studies (4, 8, 9) that pinocytosis contributes to the high permeability of capillaries of the stria vascularis under normal and experimental acute hypertensive and acute hypotensive conditions.
Animals↗
Differential actions of albumin and plasma on capillary solute permeability.
We tested the hypothesis that albumin regulates the solute permeability coefficients (Ps) of individually perfused exchange microvessels of the frog mesentery by mechanisms similar to those described for hydraulic conductivity. Using unbound Evans blue dye (T-1824, mol wt 960, 1.3 nm radius) as a test solute, we demonstrated a hysteresis of PT-1824s on luminal albumin content as perfusate albumin concentration was first reduced in three steps from 1 mg/ml to zero and then returned to 1 mg/ml. PT-1824 s did not return to initial control values. The same result was found with tetramethylrhodamine isothiocyanate-alpha-lactalbumin (mol wt 14,176; 2.0 nm radius) even when the perfusate albumin concentration was increased by 10-fold to 10 mg/ml. In contrast, frog plasma at the same total protein concentration restored P alpha-lactalbumin s to values below those measured with control albumin perfusates before Ringer perfusion. Our results conform to the hypothesis that a plasma factor (possibly orosomucoid) that modifies the charge selectivity of the microvessel wall is removed from the microvessel membrane during protein-free Ringer perfusion and is not restored by reperfusion with albumin alone.
Animals↗
Effects of inhaled NO and inhibition of endogenous NO synthesis in oxidant-induced acute lung injury.
Inhaled nitric oxide (NO) decreases pulmonary arterial pressure (Ppa) and improves oxygenation in the adult respiratory distress syndrome. Endogenous NO can modulate the development of acute tissue injury. We investigated the effects of inhaled NO and of inhibition of endogenous NO synthase in oxidant-induced acute lung injury in the isolated buffer-perfused rabbit lung. A rapid (45 min) and a more gradual (3 h) model of oxidant-induced acute lung injury were developed using the production of superoxide free radicals from the reaction of purine with low and high doses of xanthine oxidase, respectively. The effects of rapid injury included increases in Ppa, precapillary pulmonary vascular resistance, capillary filtration coefficient (Kfc), and lung weight. In the gradual-injury model, only lung weight and Kfc increased. Pretreatment with inhaled NO (90-120 ppm) prevented the rise in Ppa and precapillary pulmonary vascular resistance in the rapid-injury model and prevented elevation of Kfc in the gradual-injury model. Pretreatment with an inhibitor of endogenous NO synthase (NG-nitro-L-arginine methyl ester) resulted in increased pulmonary capillary pressure and postcapillary pulmonary vascular resistance in the rapid-injury model and increased peak Ppa, pulmonary capillary pressure, and pulmonary vascular resistance in the gradual-injury model. These data suggest that in oxidant-induced acute lung injury 1) inhaled NO may attenuate increases in capillary permeability and 2) endogenous NO may function as a modulator of pulmonary vascular tone without affecting capillary permeability.
Administration, Inhalation↗
Studies on Vaccinium myrtillus anthocyanosides. I. Vasoprotective and antiinflammatory activity.
A Vaccinium myrtillus anthocyanosides preparation (equivalent to 25% of anthocyanidins) demonstrated significant vasoprotective and antioedema properties in exerimental animals. In rabbits, the skin capillary permeability increase, due to chloroform, was reduced both after i.p. (25--100 mg/kg) and oral administration (200--400 mg/kg) of anthocyanosides. Their activity was more lasting in comparison to rutin or mepyramine and this did not seem to be due to a specific antagonism towards inflammatory process mediators such as histamine or bradykinin. Experiments carried out in rats demonstrated that Vacinium myrtillus anthocyanosides were effective both in skin capillary permeability test as well as on vascular resistance of rats fed a P factor deficient diet. In the former test effective doses were in the range of 25--100 mg/kg (by oral route). In both the animal species investigated, anthocyanosides were two-fold more active when compared to the flavonoid rutin. Vaccinium myrtillus anthocyanosides by oral route inhibited carrageein paw oedema in rats showing a dose-response relationship. An antioedema activity was detected also after i.v. or topical application.
Animals↗
Serum factors other than albumin are needed for the maintenance of normal capillary permselectivity in rat hindlimb muscle.
To investigate the effects of different perfusates on capillary permeability, we determined the capillary filtration coefficient (CFC), the capillary diffusion capacity (PS) for Cr-EDTA and clearance of albumin during isogravimetric conditions and maximal vasodilatation in the isolated, perfused rat hindquarter preparation. Experiments were conducted in 30 rats with different perfusates. We were able to confirm the classical 'protein effect'. Absence of proteins, using pure dextran solution as perfusate, induced a 45% increase in CFC and a three-fold increase in albumin clearance. However, we also found evidence for a 'serum effect'. Hence, the clearance of albumin was normal when the serum content exceeded 5% (v/v) in perfusates otherwise composed of albumin in Tyrode, but increased three-fold from 0.0305 to 0.0912 ml (min X 100 g)-1 when the rats were perfused with albumin in Tyrode with no serum present, without any change in CFC, PS for Cr-EDTA or vascular resistance to flow. Thus, certain non-dialysable serum factors, other than albumin, seem to be needed for the maintenance of normal capillary permselectivity in rat hindquarters. These factors are probably needed for the capillary membrane to maintain its character of a negatively charged barrier.
Animals↗
Evaluation of the 'stretched pore phenomenon' in isolated rat hindquarters.
In order to study the changes in capillary permeability occurring upon marked elevations in microvascular pressure, capillary filtration coefficient (CFC) and diffusion capacity (PS) for Cr-EDTA were repeatedly measured 'on-line' before and after brief periods (3 min) of large venous pressure (PV) elevations in maximally vasodilated perfused rat hindquarters. First at PV's greater than or equal to 55 mmHg, increases in CFC and Ps-Cr-EDTA were observed immediately after the pressure elevations. While the CFC increases were then always pronounced (up to 4-to 5-fold), the concomitant increases in Ps-Cr-EDTA were small (at most 30-40%). For PV greater than or equal to 55 mmHg there was a rough proportionality between PV and CFC. While PS for Cr-EDTA showed little reversibility with time upon PV normalization, CFC was usually almost completely reversed after 10-20 min. The mentioned CFC and PS increases at PV's greater than or equal to 55 mmHg were quantitatively similar to those induced by histamine-type mediators in the same preparation. It is concluded that capillary hydraulic conductivity can increase markedly but reversibly upon large PV elevations, and that this is mainly due to forceful opening of ordinarily closed 'large pores' in the microvascular membrane, rather than being caused by lesional rifts in the endothelium.
Animals↗
Permeability of single capillaries.
The development and use of electrophysiological methods in the study of the permeability of single capillaries are described. On the whole, the values obtained with single vessels correspond satisfactorily to those obtained from whole organs by use of tracer techniques. The findings support the contention that whole organ techniques allow assessment of capillary permeability with a reasonable accuracy. There is a large range of small solute permeabilities among different 'continuous' capillaries spanning from 7 x 10(-4) cm sec-1 in the mesentery to 3 x 10(-7) cm sec-1 in the brain. The finding of different permeabilities between capillaries in various organs can be rationalised in terms of the pore theory. Thus the results comply with a physical membrane having pore densities ranging from 10 per micron2 (mesentery) to 0.01 per micron2 (brain). Since-in all likelihood-ion permeation primarily takes place via the junctional zones between endothelial cells these differences probably refer to subtle differences in the nature and complexity of junctional contacts.
Animals↗