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[The alterations of serum colloid osmotic pressure, serum protein and water balance during prolonged anesthesia].

The changes of serum colloid osmotic pressure (COPm), serum protein and water balance were examined in 9 patients during and for 2 weeks after operation which required prolonged anesthesia. The values of serum total protein (TP), serum albumin (Alb) and COPm decreased by about 17% three hours after the start of anesthesia and by 15%, 20% and 24%, respectively, after 18 hours. These values returned to each preoperative value about one week after the operation. The correlation coefficients (the values in parentheses were calculated using data obtained during anesthesia) comparing COPm to TP, Alb and calculated colloid osmotic pressure (Landis' equation) were 0.661 (0.710), 0.480 (0.649) and 0.666 (0.727). There was no correlation between COPm and water balance. When COPm was 17.5mmHg or lower, calculated colloid osmotic pressure value was higher than COPm as the Alb/TP ratio decreased. Decreases in the values of COPm and serum protein during operation were considered to have been caused mainly by increased capillary permeability.

Anesthesia↗

Extravascular circulation of plasma proteins.

The escape of radioiodinated serum albumin (RISA) from the circulation and lymphatic albumin transport was investigated in anaesthetized rabbits. The fraction of RISA escaping each hour from the circulation was 0.0932 +/- 0.0075, lymphatic albumin transport in the thoracic duct was 0.0389 +/- 0.0026 in the hepatic lymph trunk 0.0115 +/- 0.016, in the intestinal trunk 0.0122 +/- 0.0037 and in the renal lymphatics 0.0185 +/- 0.0021. About 78% of the lymph and 91% of albumin transported by the thoracic duct originated from the abdominal and renal lymphatics. The ratio of albumin escape from the circulation versus lymphatic return was 2.36. From the first slopes of the lymphatic RISA activity curves the albumin escape rates were calculated and found to be 1.89 in the liver, 2.32 in the kidney, 0.69 in the intestine and 0.20 g h-1 kg-1 tissue weight in the leg (skin). The lymph vessels returned 17% of the escaped albumin, from the liver about 12% from the intestines and almost all from the kidneys. A very strong correlation (r = 0.996) was found between lymph to plasma albumin concentration ratios and the first slopes of the RISA equilibration curves, proving that protein concentration in the lymph is determined by the rate of protein escape from the capillaries and that the rates obtained from the first slopes of the RISA cpm/g albumin in lymph per RISA cpm/g albumin in plasma equilibration curves are a measure of capillary permeability to protein.

Animals↗

[Dynamic pulmonary scintigraphy with Tc99m radioaerosol for the evaluation of the permeability of the alveolo-capillary barrier].

Pulmonary clearance of small droplet 99mTc-DTPA radioaerosol was studied in 100 patients (12 normal subjects, N; 10 asymptomatic healthy smokers, FA; 31 patients with interstitial lung diseases, IP; 47 patients with chronic obstructive lung disease, BPCO). The first seven minutes of clearance were described with the function At = Ao*exp (-K*t) and the time constant K was considered representative of the 99mTc-DTPA clearance rate and hence of the alveolar-capillary barrier permeability. Groups FA, IP and BPCO showed a significant (p less than 0.05) or a highly significant (p less than 0.01) increase in permeability when compared to group N. No correlation was found between permeability and bronchial obstruction tests. The following conclusions were drawn: --99mTc-DTPA dynamic lung scanning is an easy, non-invasive method to assess derangements of alveolar-capillary barrier permeability secondary to epithelial damage; --permeability increase is a very early effect of cigarette smoke damage to the epithelium; --other mechanisms of epithelial injury are present in diffuse lung disease; --while the clinical role of this new pathophysiological test is not yet clear, it is likely that it may become a very early marker of pulmonary epithelial damage in diffuse lung disease.

Adult↗

Blood-tissue transport of substrates in the heart: studies by single circulation tracer dilution.

Passive capillary permeability is usually not the rate limiting step to movement of small lipid-insoluble molecules from plasma into the heart. At physiological concentrations the rate of carrier-mediated transport and or receptor binding of blood-borne substrates is often measurable in a single circulation through the coronary bed. Here I review some studies on uptake measured by the single-circulation multiple tracer dilution technique. The method consists of a sudden intra-arterial injection of a mixture of tracers followed by sequential rapid sampling of the venous outflow. Generally the tracers include a molecule confined to the intravascular space (e.g. albumin), another confined to the extracellular space and a third test tracer. The data analysis can give information about: a) capillary permeability-surface product (PS), b) endothelial cell membrane transport, c) the size of the interstitial space, d) transport across the sarcolemma, e) uptake by nerve endings, f) binding to receptors, g) rapid metabolic transformations. Studies were performed in the isolated perfused heart (dog and rabbit). Early observations on rapid tissue uptake of potassium and ouabain have recently been extended. Kinetics of unidirectional trans-sarcolemmal influx of lactate, a metabolic substrate for the myocardium and the neuronal uptake of amines, were investigated as well as the myocardium and the neuronal uptake of amines, were investigated as well as the effects of specific inhibitors for these transport mechanisms. Uptake was also measured for glucose, the amino acids L-phenylalanine, L-alanine and taurine; and for acetate and palmitate. Recent literature which proposes an important role for uptake and metabolism of adenosine by the endothelium is discussed. These studies are of interest for clinical applications such as positron emission tomography (PET) which makes use of short-life isotopes.

Amines↗

The use of PFC exchange transfused rats in studies of lung microvascular permeability.

The fluorocarbon exchange transfused rat was used to examine the effect of varying concentrations of circulating proteins on the permeability of pulmonary endothelium to inject ferritin. There is a significant inverse relationship between protein concentration and the relative number of vesicles containing ferritin as well as the amount of ferritin in the basement membrane. A hysteresis effect of the amount of circulating protein on the permeability of endothelium to ferritin was noted. In repletion experiments almost 2.5 times more protein was required to maintain capillary permeability at normal levels than during depletion experiments.

Animals↗

Distribution of myocardial blood flow and capillary diffusion capacity across the canine heart wall.

Myocardial capillary permeability was determined in 20 dogs by applying a new method which resembles the tissue-uptake technique. The method consisted of a bolus injection of 51Cr-EDTA into the left atrium, determination of the average arterial tracer concentration and subsequent assay of myocardial tissue activity 10, 20 and 30 s after injection. Under the fundamental assumption of no back-diffusion of tracer to capillary blood, uptake of 51Cr-EDTA into myocardium allowed calculation of the transfer constant, Kin, independent of blood flow. Regional plasma flow, fpl, was simultaneously determined from tissue content and average arterial concentration of radioactive microspheres and haematocrit. From estimates of Kin and fpl the fractional extraction, E, of 51Cr-EDTA was calculated as E = Kin/fpl. The capillary permeability-surface area product, PS, was calculated as PS = -fpl X k X 1n (1 - E). Constant fractional extraction of 51Cr-EDTA indicates that the method can be employed 10 to 20 s after injection without risk of back-diffusion. From tissue samples taken from subendocardial and subepicardial layers of the left and right ventricular walls and from left and right side parts of the septal region we measured similar PS values. Letting capillary surface area, S, equal 500 cm2 X -1 the permeability coefficient for 51Cr-EDTA was 1.39 X 10(-5) cm X s-1.

Animals↗

Blood-brain exchange routes and distribution of 65Zn in rat brain.

Zinc is essential for normal development and function of the CNS although much is to be learned about brain Zn homeostasis. In these experiments adult male Wistar rats within the weight range 500-600 g were used. Ventriculo-cisternal perfusion was performed to allow the measurement of 65Zn fluxes between blood and csf across the choroid plexuses. Blood-brain or blood-cerebrospinal fluid barrier permeability to 65Zn has been determined by graphical analysis in experiments that lasted between 5 and 180 minutes. Cerebral capillary permeability to 65Zn was found to be low with a K(in) of about 5 x 10(-4)ml/min/g. Choroid plexus permeability to 65Zn was about 12 fold greater, although Zn influx to brain via this route was less than 5% that across cerebral capillaries. The autoradiographic distribution of 65Zn in brain showed regional variation with lowest levels in white matter and high levels in the dentate gyrus and hippocampus.

Animals↗

Effect of phalloidin on structure and permeability of rete capillaries in the normal and hypoxic state.

The effects of 10(-6) M phalloidin on reperfusion-injured blood capillary structure and permeability were studied in the countercurrent perfused rete mirabile of the eel swim bladder. In the normal rete, the addition of phalloidin to the perfusion medium did not induce morphological or functional changes. When flow was arrested for 30 minutes, during which time the capillaries were exposed to inhibitors of ATP generation, and flow was then resumed with an oxygenated medium, cell membrane blebs and vacuolization, mitochondrial swelling, pericyte shrinkage, and interstitial space edema were observed. The permeability coefficients for labeled albumin, sucrose, and sodium increased to three to four times baseline values, whereas the permeability to water was not significantly modified. When the same protocol was repeated with phalloidin present in the medium throughout the experiment, the structural integrity of the endothelial cells was completely preserved and pericyte shrinkage was abolished, but interstitial space edema still occurred. The permeability to albumin, sucrose, and sodium increased only to 1.5 times baseline values, a significantly decreased increment in comparison with the experiments performed without phalloidin. We concluded that although phalloidin does not improve the capillary barrier of the normal rete, it provides protection against the structural and functional damage induced by hypoxia and reperfusion.

Air Sacs↗

[Resuscitation and extravascular lung fluid in cardiac surgery].

Cardiovascular arrest may be followed by severe respiratory insufficiency due to an increase in the pressure in the pulmonary vascular system, an alteration in capillary permeability, or both. Extracorporeal circulation (ECC), on the other hand, can lead to a change in capillary integrity ('capillary leakage') caused by the unphysiologic perfusion patterns and/or activation of various mediator systems. Pulmonary hyperhydration (increased extravascular lung water [EVLW]) seems to be the most important factor limiting pulmonary function in this situation. This retrospective study was designed to investigate the influence of resuscitation in the period before ECC on pulmonary EVLW thereafter. Eight coronary surgery patients who had to be resuscitated in the period before the start of ECC due to cardiocirculatory arrest were compared to 8 patients without resuscitation selected randomly (control group). There were no differences between the two groups with regard to age, catheterization data, and ECC conditions. All patients underwent identical monitoring, including estimation of EVLW. Lung water measurement was performed by the thermal dye technique with indocyanine green (= non-diffusible indicator) dissolved in ice-cold dextrose (= diffusible indicator) and a bedside microprocessor before resusciation and after ECC (15 min, 45 min, 5h). Simultaneously, hemodynamics and parameters of pulmonary gas exchange were monitored. Baseline values of EVLW were comparable in both groups. After ECC a transient increase in EVLW could be demonstrated in the controls, indicating an altered fluid flux even in 'uncomplicated' courses; 5 h after ECC lung water content had again reached baseline values. In contrast, there was a significant increase in EVLW in the 'complicated group' immediately after ECC (+2.60 ml/kg) and 5 h after ECC (+1.38 ml/kg); in consequence, the paO2 was significantly decreased (-180 mmHg) while Qs/Qt was increased (+6.79%). It is concluded that the combination of two factors that potentially damage pulmonary tissue and increase lung water content (reanimation due to circulatory arrest and extracorporeal circulation) lead to a significant increase in extravascular lung water combined with a deterioration of pulmonary function, resulting in severe respiratory failure.

Capillary Permeability↗

A comparison of two catalase preparations used to examine vascular permeability.

Beef liver catalase has been used as a tracer in cytochemical studies of vascular permeability. The use of Sigma catalase C-40 and C-100 preparations in capillary permeability studies of the ileojejunum and choriocapillaris was examined. Catalase C-40 is restricted by the fenestrated capillaries of the ileojejunum in contrast to their permeability to C-100. The choriocapillaris restricts both catalase preparations. Sephadex G-200 chromatography of plasma samples incubated with catalase C-40, or from C-40-injected animals, demonstrated an increase in the molecular weight of the tracer. No increase in molecular weight was evident for catalase C-100. The isoelectric point of both preparations was 5.4-5.7. These findings indicate that Sigma catalase C-100 is the preferred preparation for use in vascular permeability studies.

Animals↗

Evaluation of lung clearance of inhaled pertechnegas.

Pertechnegas is a new ventilation agent produced by modifying the atmosphere of combustion of Technegas. Due to its rapid disappearance from the lungs, Pertechnegas has been suggested as useful in measuring pulmonary epithelial permeability. This study aimed to assess the reliability of ventilation scans with Pertechnegas to evaluate alveolar-capillary permeability. Six non-smokers with no evidence of pulmonary disease were investigated. Scintigraphic data were used to evaluate the site of Pertechnegas deposition (by assessing the Penetration Index [PI] of the gas), its clearance rate (by calculating the time to half-clearance [T1/2]) and its lung distribution (by means of a pixel-by-pixel analysis. PI measurements produced a mean value of 88.8 +/- 13.3% (range 69-117%). Time activity curves showed a fast clearance in all cases (mean T1/2 = 10.7 +/- 2.1 min, range 8.1-14.3 min). Comparison of statistical indices of uniform deposition (skewness and kurtosis) indicated satisfactory homogeneity of Pertechnegas distribution throughout the lungs. These data show that after inhalation Pertechnegas has a peripheral deposition and a homogeneous distribution in the lungs and is rapidly cleared through the alveolar-capillary barrier. In conclusion Pertechnegas can be recommended as a potential radiopharmaceutical for studying the pulmonary epithelial barrier.

Capillary Permeability↗

Inhibition by various substances of oedema formation in the bind-paw of the rat induced by 5-hydroxytryptamine, histamine, dextran, egg-white and compound 48/80.

Of the substances studied for their inhibitory action of the oedema formation in the hind-paw of the rat, the most active was a new derivative of phenothiazine, related to chlorpromazine. It is methotrimeprazine {10-(3-dimethylamino-2-methylpropyl)-2-methoxyphenothiazine; 7044 RP}. This substance possesses potent antihistamine and anti-5-hydroxytryptamine properties, and doses of 0.25 mg./kg. inhibited the blueing and swelling of the foot after injections of histamine, 5-hydroxytryptamine, eggwhite, dextran or compound 48/80 into the feet of rats with sulphan blue (Evan's blue) dye in their circulation. The results indicate that both histamine and 5-hydroxytryptamine play rôles in increasing capillary permeability in the rat.

Animals↗

Gallium-transferrin as a macromolecular tracer of vascular permeability.

Labeling of plasma transferrin with gallium was investigated to determine whether the gallium-transferrin complex could be effectively used as a macromolecular tracer in studies of capillary permeability using Positron Emission Tomography (PET). Three gallium-plasma preparations were tested and 2 h biodistribution studies were performed in rats. The three preparations gave similar blood clearance and tissue distribution data, but the methods used for evaluating gallium-transferrin binding were found to be suboptimal. Gallium clearance from blood was biexpoential with both components faster than that of 125I-albumin. Gallium distribution spaces in all tissues including intracerebral Walker-256 tumors were larger than those of albumin. These results indicate a relative instability of the gallium-transferrin complex in vivo, which appears to preclude its use as an acceptable radiolabeled protein for vascular permeability studies using PET.

Animals↗

Diffusion permeability of an isolated rete mirabile.

The rete mirabile of the swimbladder of the eeel is a countercurrent exchange organ composed of alternately disposed and venous capillaries. A countercurrent perfusion of these was set up by isolating arterial input and outflow, and venous input and outflow, and perfusing each set of capillaries with oxygenated albumin-containing Krebs-Ringer bicarbonate buffer. Constant arterial infusions containing tracer albumin, inulin, 3-O-methylglucose, urea, and water were begun and tracer concentrations at the outlets of arterial and venous beds were determined. Capillary permeabilities were determined from the resulting steady state values. The method of calculation of permeability values from the data acquired in the rete involves no approximations and appears to yield unequivocal values. For the solutes, the values appear compatible with transcapillary passage by free diffusion. No evidence of increasing restriction (in comparison to the diffuse coefficients) was found over the range of molecular sizes explored. The permeability for labeled water, in relation to the solutes, was too high, and this augmentation was attributed to the larger surface available for its exchange. Despite this larger value, labeled water did not undergo flow-limited exchange. A significant barrier to its distribution is present in this capillary system.

Air Sacs↗

Respiratory failure following anti-lung serum: study on mechanisms associated with surfactant system damage.

Within 2 minutes intravenous anti-lung serum (ALS) into guinea pig induces a respiratory failure that is fatal within 30 min. The relationship between surfactant, alveolar-capillary permeability and respiratory failure was studied. Within two minutes ALS induced a leak in the alveolar-capillary barrier. Within 30 minutes 28.3% (controls, given normal rabbit serum: 0.7%) of iv 131I-albumin, and 0.5% (controls 0.02%) of iv surfactant phospholipid tracer were recovered in bronchoalveolar lavage. Furthermore, 57% (controls 32%) of the endotracheally administered surfactant phospholipid became associated with lung tissue and only less than 0.5% left the lung. The distribution of proteins and phospholipids between the in vivo small volume bronchoalveolar lavages and the ex vivo bronchoalveolar lavages were dissimilar: 84% (controls 20%) of intravenously injected, lavageable 131I-albumin and 23% (controls 18%) of total lavageable phospholipid were recovered in the in vivo small volume bronchoalveolar lavages. ALS also decreased lavageable surfactant phospholipid by 41%. After ALS the minimum surface tension increased. The supernatant of the lavage increased the minimum surface tension of normal surfactant. In addition, the sediment fraction of the lavage had slow surface adsorption, and a marked reduction in 35,000 and 10,000 MW peptides. Exogenous surfactant ameliorated the ALS-induced respiratory failure. We propose that inhibition, altered intrapulmonary distribution, and dissociation of protein and phospholipid components of surfactant are important in early pathogenesis of acute respiratory failure.

Animals↗