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PubMed1992

Microcirculation in systemic hypertension.

In 40 patients with idiopathic systemic hypertension, skin blood flow was evaluated with laser-Doppler flowmetry, transcutaneous measurements of partial pressure of oxygen (PO2) and partial pressure of carbon dioxide (PCO2), and determination of capillary permeability before and after treatment with nifedipine (10 mg tid for four weeks). Also 35 normal subjects matched for age and sex distribution were studied. Before treatment, microcirculatory studies showed a significant decrease in skin flow and venoarteriolar response in hypertensive patients in comparison with normal subjects. Moreover, PO2, PCO2, and capillary permeability were significantly lower in hypertensives. All these microcirculatory parameters significantly increased after nifedipine treatment while both systolic and diastolic pressures decreased. In conclusion, laser-Doppler flowmetry used with other microcirculatory techniques was able to discriminate between normal subjects and hypertensive patients, and it was able to show the improvement in the microcirculation after nifedipine treatment.

Adult↗
PubMed2005

Cancer growth and spread are saltatory and phase-locked to the reproductive cycle through mediators of angiogenesis.

The frequency of breast cancer metastatic spread is affected by the menstrual cycle phase of its resection. Breast cancer growth, post-resection spread, and cure frequency are each modulated by the estrous cycle in C(3)HeB/FeJ mice. Tumor metastases are 2- to 3-fold more frequent when the resection is done during diestrus as compared with estrus. Tumor angiogenesis is essential for both cancer growth and lethal metastatic cancer spread. The balance between vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) modulates new blood vessel formation and blood vessel permeability. Sex hormones modulate the expression of these key angiogenesis regulators in the endometrium and uterus. We, therefore, asked whether the estrous cycle modulates the density of CD31-positive vessels within the tumor, the permeability of tumor blood vessels, levels of VEGF and bFGF immunoreactive protein in normal breast and breast cancer, and whether expression of these genes are modulated by the estrous cycle stage in C(3)HeB/FeJ mice. We find that tumor blood vessel density and blood volume do not vary throughout the cycle; however, tumor capillary permeability is regulated by the estrous cycle being highest in diestrus, the cycle stage associated with the highest cancer growth rate and the highest frequency of post-resection cancer metastasis. VEGF protein levels in breast cancer are >100-fold higher than in normal breast. VEGF protein in this mammary tumor varies with the estrus cycle with highest levels in proestrus. In a non-breast tumor, methylcholantrenene A sarcoma, from CD(2)F(1) mice, tumor VEGF protein also varies with the estrus cycle with highest levels in proestrus and diestrus. VEGF gene expression in the mammary tumor does not change significantly across the cycle, but is modulated by the cycle in normal breast tissue. bFGF protein concentration is 6-fold higher in normal breast than in breast cancer. bFGF protein pattern in both tumor and breast are similar, opposite to VEGF, and affected by oophorectomy. bFGF message is modulated by the cycle in both breast cancer and normal breast. The changes in breast cancer capillary permeability, VEGF, and bFGF that occur during each fertility cycle, in breast tissue and breast cancer, putatively in response to cyclical changes in sex hormones, might contribute, at least in part, to both the modulation of cancer growth and post-resection breast cancer spread by the fertility cycle. These fertility cycle-induced effects on tumor biology also seem to extend to non-breast cancer biology.

Animals↗
PubMedDate not supplied

[Disorders of microcirculation in diffuse toxic goiter and their correction in the early postoperative period].

A study was made of microcirculation in 45 patients suffering from diffuse toxic goiter at the early postoperative period with the aid of microphotography of the bulbar conjunctiva vessels, and investigation of the rate of the isotope elimination from the intradermal depot and the capillary permeability by V. P. Kaznacheev's method. The data obtained permitted to draw a conclusion that on admission to the clinic patients with toxic goiter were suffering from arteriolar spasm, had poor vascular pattern in the bulbar conjunctiva, the sledge phenomenon in small venules, an acceleration of the isotope elimination from the intradermal depot and an increase of the capillary permeability. Preoperative preparation improved the microcirculation indices, without completely normalizing them, however. Microcirculatory disturbances reached their maximum the first two days after the operation and declined by the 3rd-5th day. Recommendations on correction of the microcirculatory disturbances are given.

Adolescent↗
PubMed1957

A comparative study of kinin, kallidin, and bradykinin.

Partially purified kinin, a polypeptide in wasp venom, has been found to be a potent smooth-muscle stimulating and hypotensive agent. Such a preparation was 10 to 100 times more effective than histamine in enhancing capillary permeability on intradermal injection, and 10 times more effective than acetylcholine in evoking pain on a cutaneous blister base. Some differences between the actions of salivary kallikrein and trypsin in releasing kallidin or bradykinin have been observed, and some modifications of previous methods of preparing crude kallidin and bradykinin are suggested. Kallidin and bradykinin are effective enhancers of capillary permeability in the guinea-pig and rabbit. Chemical and pharmacological tests failed to differentiate between kallidin and bradykinin which must be, therefore, closely similar compounds. The possible role of kallidin and bradykinin in physiological or pathological conditions is discussed.

Acetylcholine↗
PubMed1979

Relationship of burn size to vascular permeability changes in rats.

Studies to determine the relationship between increased vascular permeability, water content and protein leakage, and burn size were performed on rats. Partial thickness scald burn covering 10, 20, 30 and 40 per cent of the rats' body surface area were induced in four groups of rats. A fifth group of rats served as the controls. Following the burn, all rats received intravenously fluid resuscitation. Burn edema was maximal at three hours postburn for the 30 and 40 per cent groups. The edema persisted throughout the 24 hour study period. No significant change in water content of unburned skin was demonstrated. Albumin leakage into injuried tissues was maximal at 30 minutes and disappeared by 12 hours postinjury. The size of the burn had no effect on 131Risa leakage into injuried tissues. Albumin leakage into noninjured tissues occurred only in the 30 and 40 per cent burn groups was mild compared with that in burned tissues and also disappeared by 12 hours postburn. Extravasation of albumin in lung, liver, spleen, kidney and muscle was mild and seen only in the 30 and 40 per cent burn groups. Except for a mild increase in water content of lung tissue in the 30 and 40 per cent groups only, no consistent increase in the water content of other organs was observed. While the size of the burn appears to have some influence on capillary permeability, burns up to 40 per cent of the body surface have only a mild and transient effect upon capillaries distant to the site of injury. This observation supports the concept of a humoral mediator for capillary permeability and suggests that more pronounced changes can occur with larger burns. Nonetheless, extravasation of albumin appears to be short-lived.

Animals↗
PubMed1978

[Muscle blood flow and capillary diffusion capacity in patients with rheumatoid arthritis (author's transl)].

Capillary blood flow (Xenon-133) and diffusion capacity for Chrom-51-EDTA (PS-Product of Renkin) of striated muscle tissue were examined by double isotope method in patients with rheumatoid arthritis. Xenon-Clearance and PS-Product were studied under normal conditions and following hyperemisation. There existed no significant difference between rheumatoid patients and normal subjects and there was no evidence of increased capillary permeability. Apparently, derangement of muscle capillaries is rare in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed2006

Passing on the legacy: teaching capillary filtration and developing presentation skills using classic papers.

Capillary filtration is a key area in the understanding of cardiovascular function and has both physiological and pathophysiological relevance in nearly every organ system. This article describes how classic papers in the Legacy collection of American Physiological Society publications can be used in a teaching symposium exploring the evidence supporting current concepts of capillary fluid exchange. Individual students are given papers to read, edit, and present to the class. The appropriate selection and sequencing of these papers allows the development of important physiological concepts to be tracked. A series of papers concerned with capillary filtration is suggested, and the contribution of each to the developing story is outlined. This approach allows students to develop critical and presentation skills and provides them with a case study of the scientific method as it is applied to physiology as well as establishing an appropriate knowledge base concerning the role of hydrostatic and oncotic forces in capillary fluid exchange. Relevant teaching points are explored further using questions based on a figure from one of the three classic papers used: "Microinjection studies of capillary permeability: II. The relationship between capillary pressure and the rate at which fluid passes through the walls of single capillaries," by E. M. Landis (Am J Physiol 82: 217-238, 1927).

Capillary Permeability↗
PubMed1989

Chest wall restriction limits high airway pressure-induced lung injury in young rabbits.

High peak inspiratory pressures (PIP) during mechanical ventilation can induce lung injury. In the present study we compare the respective roles of high tidal volume with high PIP in intact immature rabbits to determine whether the increase in capillary permeability is the result of overdistension of the lung or direct pressure effects. New Zealand White rabbits were assigned to one of three protocols, which produced different degrees of inspiratory volume limitation: intact closed-chest animals (CC), closed-chest animals with a full-body plaster cast (C), and isolated excised lungs (IL). The intact animals were ventilated at 15, 30, or 45 cmH2O PIP for 1 h, and the lungs of the CC and C groups were placed in an isolated lung perfusion system. Microvascular permeability was evaluated using the capillary filtration coefficient (Kfc). Base-line Kfc for isolated lungs before ventilation was 0.33 +/- 0.31 ml.min-1.cmH2O-1.100g-1 and was not different from the Kfc in the CC group ventilated with 15 cmH2O PIP. Kfc increased by 850% after ventilation with only 15 cmH2O PIP in the unrestricted IL group, and in the CC group Kfc increased by 31% after 30 cmH2O PIP and 430% after 45 cmH2O PIP. Inspiratory volume limitation by the plaster cast in the C group prevented any significant increase in Kfc at the PIP values used. These data indicate that volume distension of the lung rather than high PIP per se produces microvascular damage in the immature rabbit lung.

Animals↗
PubMed2003

The pharmacokinetics of the interstitial space in humans.

BACKGROUND: The pharmacokinetics of extracellular solutes is determined by the blood-tissue exchange kinetics and the volume of distribution in the interstitial space in the different organs. This information can be used to develop a general physiologically based pharmacokinetic (PBPK) model applicable to most extracellular solutes. METHODS: The human pharmacokinetic literature was surveyed to tabulate the steady state and equilibrium volume of distribution of the solutes mannitol, EDTA, morphine-6-glucuronide, morphine-3-glucuronide, inulin and beta-lactam antibiotics with a range of protein binding (amoxicillin, piperacillin, cefatrizine, ceforanide, flucloxacillin, dicloxacillin). A PBPK data set was developed for extracellular solutes based on the literature for interstitial organ volumes. The program PKQuest was used to generate the PBPK model predictions. The pharmacokinetics of the protein (albumin) bound beta-lactam antibiotics were characterized by two parameters: 1) the free fraction of the solute in plasma; 2) the interstitial albumin concentration. A new approach to estimating the capillary permeability is described, based on the pharmacokinetics of the highly protein bound antibiotics. RESULTS: About 42% of the total body water is extracellular. There is a large variation in the organ distribution of this water - varying from about 13% of total tissue water for skeletal muscle, up to 70% for skin and connective tissue. The weakly bound antibiotics have flow limited capillary-tissue exchange kinetics. The highly protein bound antibiotics have a significant capillary permeability limitation. The experimental pharmacokinetics of the 11 solutes is well described using the new PBPK data set and PKQuest. CONCLUSIONS: Only one adjustable parameter (systemic clearance) is required to completely characterize the PBPK for these extracellular solutes. Knowledge of just this systemic clearance allows one to predict the complete time course of the absolute drug concentrations in the major organs. PKQuest is freely available http://www.pkquest.com.

Animals↗
PubMed1993

Effect of alpha 1-acidglycoprotein on myocardial uptake and pharmacodynamics of quinidine in perfused rat heart.

The myocardial uptake and pharmacodynamics of quinidine were examined in the isolated perfused rat heart preparation under conditions of varying concentrations of bovine alpha 1-acidglycoprotein (AAG) in the perfusate. Three hearts were perfused for five consecutive 35 min phases with buffer containing quinidine and AAG in concentrations of 0, 0.1, 0.5, 1.5 and 0 g/L, in that order, with a 55 min washout period between each phase. The equilibration rate constant for the quinidine output concentration increased with increasing AAG concentration, but not as much as predicted by the conventional pharmacokinetic uptake model, which assumes constant capillary permeability among the phases. Estimates of the permeability surface product for the two zero AAG phases (17.7 +/- 1.91 and 19.1 +/- 0.82 mL/min/g) were significantly greater than those for the three AAG phases (8.94 +/- 0.99, 8.70 +/- 0.26, 9.01 +/- 0.26 mL/min/g; P < 0.05). This effect of AAG is the same as that observed previously by us with bovine serum albumin in this same experimental preparation. This suggests that the mechanism of reduced capillary permeability is the same for both proteins, i.e., the formation of a steric barrier to paracellular transport rather than an electrostatic barrier. There was a direct, linear relationship between lengthening of the QT interval of the electrocardiogram and total and unbound quinidine concentrations, but the relationship for unbound concentration was independent of quinidine unbound fraction. Therefore, the electrocardiogram effect of quinidine was directly related to the circulating unbound rather than total drug concentration.

Animals↗
PubMed1988

Pulmonary effects of crystalloid and colloid resuscitation from hemorrhagic shock in the presence of oleic acid-induced pulmonary capillary injury in the dog.

The effects of resuscitation with crystalloid and colloid solutions in the presence of increased pulmonary capillary permeability were studied. Twenty-four hours after oleic acid administration, dogs were anesthetized and bled to produce hemorrhagic shock. One hour later, resuscitation was performed with saline, 5% albumin, or 6% hydroxyethyl starch solution to restore and then maintain cardiac output at pre-oleic acid values for 6 h. Dogs were recovered and, 24 h later, were reanesthetized for final measurements. Oleic acid administration resulted in increases in pulmonary artery pressure, pulmonary vascular resistance, and extravascular lung water (EVLW). Resuscitation from hemorrhagic shock restored pulmonary hemodynamics to pre-hemorrhage levels and did not affect EVLW, PaO2, shunt fraction, dead-space-to-tidal-volume ratio, or pulmonary compliance. There were no differences in these parameters related to the choice of resuscitation fluid. Saline resuscitation markedly reduced plasma oncotic pressure and the plasma oncotic-pulmonary artery occlusion pressure gradient. Values for these two variables were markedly lower with saline than with colloid resuscitation. The authors conclude that the pulmonary effects of crystalloid and colloid solutions are similar in the presence of moderate increases in pulmonary capillary permeability.

Animals↗
PubMed2000

Effect of hypothermic pulmonary artery flushing on capillary filtration coefficient.

BACKGROUND: We previously demonstrated that surfactant dilution and inhibition occur immediately after pulmonary artery flushing with hypothermic modified Euro-Collins solution. Consequently, we speculated that increased capillary permeability contributed to these surfactant changes. To test this hypothesis, we evaluated the effects of hypothermic pulmonary artery flushing on the pulmonary capillary filtration coefficient (Kfc), and additionally performed a biochemical analysis of surfactant. METHODS: We used a murine isolated, perfused lung model to measure the pulmonary capillary filtration coefficient and hemodynamic parameters, to determine the wet to dry weight ratio, and to evaluate surfactant by biochemical analysis of lung lavage fluid. We defined three study groups. In group I (controls), we harvested lungs without hypothermic pulmonary artery flushing, and measured Kfc immediately. In group II (in situ flush), we harvested lungs after hypothermic pulmonary artery flushing with modified Euro-Collins solution, and then measured Kfc. Experiments in groups I and II were designed to evaluate persistent changes in Kfc after pulmonary artery flushing. In group III (ex vivo flush), we flushed lungs ex vivo to evaluate transient changes in Kfc during hypothermic pulmonary artery flushing. RESULTS: Groups I and II did not differ significantly in capillary filtration coefficient and hemodynamics. Group II showed significant alterations on biochemical surfactant analysis and a significant increase in wet-to-dry weight ratio, when compared with group I. In group III, we observed a significant transient increase in capillary filtration coefficient during pulmonary artery flushing. CONCLUSIONS: Hypothermic pulmonary artery flushing transiently increases the capillary filtration coefficient, leads to an increase in the wet to dry weight ratio, and induces biochemical surfactant changes. These findings could be explained by the effects of hypothermic modified Euro-Collins solution on pulmonary capillary permeability.

Airway Resistance↗
PubMed1988

A new rhinitis model using chemical mediators in rats.

No good experimental model for studying rhinitis, has been hitherto available. In the present study, development of a new rhinitis model using chemical mediators was attempted, especially to establish an index of nasal congestion. Male Wistar rats were anesthetized with pentobarbital-Na. Nasal cavities were ventilated between both cannulae inserted into the nasopharynx and bilateral nostrils, with an artificial respirator. Intranasal resistance was recorded with a modification of a Konzett-Rössler apparatus as a change in ventilation overflow (VO). To provoke rhinitis, some mediators were inhaled into the nasal cavities with an ultrasonic nebulizer for 5 min. To assess the capillary permeability of the nasal mucosa, exudation of Evans blue was determined by injecting the dye before inhalations of mediators. Inhalation of histamine (0.01, 0.1, 0.3%), bradykinin (0.01, 0.1%) and ACh (0.3%) markedly increased VO, while inhalation of serotonin (0.01, 0.1, 0.3%) did not increase VO. Histamine, bradykinin and high concentration of ACh significantly increased the dye exudation in the nasal cavities, although serotonin did not. From the above results, it is concluded that 1) a new rhinitis model in which symptoms of nasal blockage and increased capillary permeability in nasal mucosa are quantitatively determined, was established, and 2) histamine- and bradykinin-inhalations can cause rhinitis-like symptoms, although serotonin-inhalation can not.

Airway Resistance↗
PubMed1996

Leg oedema protection from a buckwheat herb tea in patients with chronic venous insufficiency: a single-centre, randomised, double-blind, placebo-controlled clinical trial.

OBJECTIVES: The efficacy of a buckwheat herb tea was determined in patients with chronic venous insufficiency (CVI) in a single-centre, randomised, double-blind, placebo-controlled clinical trial. METHODS: Sixty-seven male and female patients (22-74 years) with CVI were randomly divided into two groups after a 2-week run-in period. They received either buckwheat herb tea (Fagopyrum esculentum) or a placebo tea for a period of 3 months. The main outcome measure was the lower leg volume determined by ultrasound. Subjective symptoms were assessed by a clinical symptom score system. The femoral vein diameters were measured by B-scan sonography. In a subgroup of patients capillary permeability was determined by cutaneous fluorescence angiography. RESULTS: Although the mean partial leg volume did not change in the treatment group (from 2041 to 2073 ml), it increased in the placebo group by 110 ml (from 1972 to 2082 ml) according to intent to treat. The difference between the groups was significant. The subjective clinical symptoms were significantly reduced in both groups. The mean diameters of the femoral veins were reduced and capillary permeability was improved, but neither change was statistically significant. No drug-related adverse effects were observed. CONCLUSION: CVI is a very placebo-sensitive condition. The treatment with buckwheat herb tea is safe and could have a favourable influence on patients with CVI such that further oedema development is prevented.

Adult↗
PubMed1983

Further evidence for hyaluronidase activity of Treponema pallidum.

The presence of hyaluronidase in preparations of Treponema pallidum was previously shown using acidified bovine serum albumin reactions and Ouchterlony immunodiffusion. To expand on these preliminary findings more sensitive techniques of viscometry, additional immunologic reactions, and altered capillary permeability were used to characterize treponemal-associated hyaluronidase. The pathogens T. pallidum and T. pertenue degraded hyaluronic acid, whereas the nonpathogens T. denticola and T. vincentii did not. As syphilitic infection progressed, hyaluronidase activity decreased; organisms harvested from 14-day testicular infections degraded hyaluronic acid less rapidly than organisms from 4-day infections. Uninfected rabbit testicular extract also exhibited significant enzyme activity. The neutralizing activity of immune sera was decreased by prior adsorption with bovine hyaluronidase, suggesting that some of the neutralizing factors are associated with this enzyme. Radioimmunoassay was used to quantitate antibodies to hyaluronidase in immune sera. Antihyaluronidase sera were isolated from rabbits immunized with bovine hyaluronidase. Treponema pallidum, as well as uninfected rabbit testicular extract, cross-reacted with these antisera. Immunofluorescence indicated that the hyaluronidase was uniformly distributed along the treponemal surface. As a final indicator of hyaluronidase activity, alterations in capillary permeability were detected 1 h after intradermal injection of T. pallidum.

Animals↗
PubMed1990

Contrast-enhanced magnetic resonance imaging of tumor-bearing mice treated with human recombinant tumor necrosis factor alpha.

Pharmacological effects of recombinant human tumor necrosis factor alpha (TNF) were studied in a mouse fibrosarcoma model using magnetic resonance imaging enhanced with a macromolecular contrast agent, albumin(gadolinium-diethylenetriamine pentaacetic acid)35. TNF was administered i.v. in a dose of 150 micrograms/kg, 60 to 80 min prior to imaging. Contrast-enhanced and nonenhanced magnetic resonance images of TNF-treated (n = 10) and untreated (n = 8) Meth A fibrosarcomas were obtained at 2.0 Tesla using T1-weighted spin-echo pulse sequences. Serial images spanning an interval of 60 to 120 min after TNF administration showed that the TNF-treated tumors enhanced significantly more overall than did untreated tumors (43% versus 31%). The most marked differential tumor enhancement was observed in the tumor rim (59% versus 40%). Nontumorous tissue, including muscle and brain, revealed no significant enhancement differences between TNF-treated animals and controls. The observed tumor enhancement corresponded strongly with Evans blue staining; the TNF-treated tumors stained deep blue, while untreated tumors and normal tissues observed did not stain. The different enhancement and Evans blue staining patterns between TNF-treated tumors and untreated tumors are attributed to TNF-induced changes in tumor capillary integrity. The data indicate that TNF effects on tumors include an increased capillary permeability for macromolecules at early times after administration. The ability to detect changes in capillary permeability in vivo using contrast-enhanced magnetic resonance imaging may prove to be clinically useful to monitor tumor response to TNF.

Animals↗