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PubMed1975

Permeability limitation in estimation of local brain blood flow with [14C]antipyrine.

Influence of capillary permeability on local cerebral blood flow (LCBF) estimated by the autoradiograhpic diffusible-indicator method was analyzed by computer simulation. Its influence increases with increasing flow. With normal perfusion rates in gray matter, capillary permeability coefficient x surface area (PS value) must exceed 0.12 cm3-s(-1)-g(-1) for estimated LCBF to attain 95% of true values in all structures. In white matter, with its lower perfusion rates, the PS value must exceed 0.035 cm3-s(-1)-g(-1) for equivalent accuracy. [14C]antipyrine, widely used in the LCBF technique, has a PS value below these values and leads to undersestimation of LCBF. Experimental studies in cats in which LCBF was measured with either [14C]antipyrine or the freely diffusible, radioactive gas, [131I]trifluoroiodomethane, demonstrated consistently lower estimates of LCBF with [14C]antipyrine than with the gas; the deviations in the various cerebral structures approximated those predicted by the theoretical analyses. These results suggest that the uptake of [14C]antipyrine by cerebral tissues is diffusion limited as well as flow limited, and it therefore is not an ideal tracer for the autoradiographic LCBF technique.

Animals↗
PubMed1994

Does the reamer type influence the degree of lung dysfunction after femoral nailing following severe trauma? An animal study.

In multiple trauma patients with lung contusion, pulmonary complications have been reported that were attributed to intramedullary stabilization of the femur. The reaming procedure of the medullary canal is thought to play a major role. We investigated whether different types of reamers might exert different amounts of fat mobilization into the vascular system and different degrees of pulmonary dysfunction. Adult female Merino sheep were submitted to hemorrhagic shock (2 h, 50 mm Hg) and a unilateral lung contusion; in addition, a lung lymph fistula was created. Pulmonary capillary permeability, central venous triglyceride levels, 11-dehydro-thromboxane B2 (dh-TXB2) levels, and pulmonary artery pressure were determined. After recovery, animals were randomly assigned to intramedullary femoral nailing using several types of reamers: group A, AO reamer (n = 8); group B, Biomet reamer (n = 7); group H, Howmedica reamer (n = 6); group C, controls, no reaming (n = 4). Intramedullary reaming caused a significant (p < 0.05) increase in pulmonary artery pressure in groups A and B; dh-TXB2 levels increased in all groups. Statistically significant (p < 0.05) pulmonary capillary permeability damage was measured in group A only. Intramedullary femoral nailing can cause transient pulmonary hemodynamic and mediator effects as well as increased pulmonary capillary permeability. In the present study, this effect was evident in group A reamer systems only, which may be due to reamer construction.

Animals↗
PubMed1986

Effect of dexamethasone on vascular function in RIF-1 tumors.

The present series of experiments was conducted to determine the effect of dexamethasone on vascular function and cell proliferation in s.c. RIF-1 tumors. 125I-BSA, 51Cr-EDTA dilution techniques were used to evaluate dexamethasone induced changes in tumor plasma water, capillary permeability, and extracellular water volumes, while 59Fe and 51Cr labeled erythrocyte techniques were used to assess changes in tumor exchangeable erythrocyte volumes. 86RbCl distribution studies were also conducted to evaluate vascular perfusion in RIF-1 tumors after dexamethasone treatment. In this corticosteroid receptor containing tumor model, dexamethasone had profound effects on all of the measured parameters of vascular function. Reduced tumor cell proliferation after dexamethasone treatments was accompanied by reduced capillary permeability, reduced interstitial water volumes, increased plasma volumes, and reduced vascular perfusion. Serial studies after dexamethasone treatments indicated that increases in vascular perfusion preceded proliferative recovery. Intervals of maximal [3H]thymidine labeling after dexamethasone were characterized by transient increases in capillary permeability, interstitial water volumes, and tumor erythrocyte exchange with the general circulation. At intervals of maximal cell proliferation (36-48 h after dex) 86RbCl distribution in tumors was about 3 times that seen in untreated controls. The results seem to indicate that, as in edematous normal tissues, dexamethasone can have profound effects on vascular function and water compartmentalization in RIF-1 tumors.

Animals↗
PubMed1997

Reduced ischemia-reperfusion injury with isoproterenol in non-heart-beating donor lungs.

Transplantation of lungs retrieved from non-heart-beating donors could expand the donor pool. Recent studies suggest that the ischemia-reperfusion injury (IRI) to the lung can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, as measured by Kfc, in lungs retrieved from non-heart-beating donors and reperfused with or without isoproterenol (iso). Using an in situ isolated perfused lung model, lungs were retrieved from non-heart-beating donor rats ventilated with O2 or not at varying intervals after death. The lungs were reperfused with or without iso (10 microM). Kfc, lung viability, and pulmonary hemodynamics were measured, and tissue levels of adenine nucleotides and cAMP were measured by HPLC. Iso-reperfusion decreased Kfc significantly (P < 0.05) compared to non-iso-reperfused groups at all postmortem ischemic times, irrespective of preharvest ventilation status. Pulmonary arterial pressures and resistances increased and venous resistances decreased with iso-reperfusion. Total adenine nucleotide (TAN) levels correlated with Kfc in non-iso-reperfused (r = 0.65) and iso-perfused (r = 0.84) lungs. cAMP levels increased significantly with iso-reperfusion. cAMP levels correlated with Kfc (r = 0.87) in iso-reperfused lungs. Iso-reperfusion of lungs retrieved from non-heart-beating donor rats results in decreased capillary permeability and increased lung tissue cAMP levels. Pharmacologic augmentation of tissue TAN and cAMP levels may further ameliorate the increased capillary permeability seen in lungs retrieved from non-heart-beating donors.

Adenine Nucleotides↗
PubMed1999

Dose-dependent increase of transcapillary diffusion of sodium fluorescein after histamine microinjections.

BACKGROUND: To study the dose-dependent effects of histamine on capillary permeability in human skin, using the microinjection technique. PATIENTS AND METHODS: Eight healthy volunteers (2 w, 6 m; mean age 33 years) were included in the study. On two separate occasions, glass microcannulas with a tip diameter of 7 to 9 microns were inserted into the subepidermal layer of the skin at the distal medial tibia surface of each lower limb with a micromanipulator. In each subject, 0.5 microliter of 3 different concentrations of histamine solution (0.1/1000, 0.01/1000 and 0.001/1000) were injected and compared to the solvent (0.9% NaCl). Transcapillary diffusion of intravenously administered Na-fluorescein was assessed simultaneously using two fluorescence videomicroscopy systems. Off-line video densitometry was performed in an area of 0.56 mm2 around the injection sites and fluorescence light intensities were measured in arbitrary units (AU) at 10, 30, 60, 120 and 600 s after dye appearance. RESULTS: Compared to the solvent histamine microinjections resulted in a dose-dependent increase of mean fluorescence light intensities (FLI). Whereas mean FLI for the 0.001/1000 histamine injection was only significantly elevated 10 min after dye appearance (p < 0.05) an increase of mean FLI was already observed 10 s after dye appearance following the 0.1/1000 histamine injection (p < 0.05), which was more pronounced at later time points (p < 0.001). Mean FLI's for the 0.01/1000 histamine solution were in between and resulted in significantly elevated values 1 min to 10 min after dye appearance (p < 0.05). CONCLUSIONS: We conclude that the microinjection technique together with fluorescence videomicroscopy described previously [6] is able to document a dose-dependent effect of histamine microinjections on skin capillary permeability. The technique may facilitate to determine appropriate dosages not only of histamine in order to test the effect of antagonists on human skin capillary permeability.

Adult↗
PubMed1994

Regional myocardial flow and capillary permeability-surface area products are nearly proportional.

Analyses of data on the transcapillary exchange and cellular uptake in the normal heart have generally been based on the assumption that local membrane conductances and volumes of distribution are everywhere the same. The question is whether such an assumption is justified in view of the marked (sixfold) heterogeneity of local blood flows per gram tissue. The method was to estimate both flow and capillary membrane permeability-surface area products (PS) locally in the heart. For each of five dogs running on a sloped treadmill, the deposition of tracer microspheres and of [131I]iodophenylpentadecanoic acid (IPPA), after left atrial injection, was determined in 256 pieces of left ventricular myocardium by killing the animals at approximately 100 s after radiotracer injection. A hydraulic occluder stopped the flow to a portion of the myocardium supplied by the left circumflex coronary artery 30 s before tracer injection. Regional flows ranged from 0.1 to 7.0 ml.g-1.min-1. IPPA extractions ranged from 20 to 49%. Using the known flows, we assumed the applicability of an axially distributed blood-tissue exchange model to estimate the PS for the capillary (PSc) and the parenchymal cell. It was impossible to explain the data if the PSc values for membrane transport were uniform throughout the organ. Rather, the only reasonable descriptors of the data required that local PSc values increase with local flow, almost in proportion. Current methods of analysis using data based on deposition methods need to be revised to take into account the near proportionality of PS to flow for at least some substrates.

Animals↗
PubMed1976

Pathogenesis of ascites in mice with peritoneal carcinomatosis.

For clarification of the mechanisms underlying formation of malignant ascites, alterations in lymphatic transport from the peritoneal cavity and in peritoneal capillary permeability to protein were studied sequentially in mice inoculated ip with Ehrlich-Lettre ascites tumor cells. All animals developed detectable ascites within 5-7 days of the injection. Diaphragmatic and retrosternal lymph vessels became radiopaque within 30 hours of the ip injection of radiopaque contrast material in control animals without ascites and in 12 experimental mice receiving contrast material 1-3 days after injection of tumor cells. No lymph vessels were opacified in 3 of 4 animals when contrast material was injected on day 5 or in any animal receiving contrast material on or after day 7 following the tumor cell injection. We determined alterations in peritoneal capillary permeability in the second group by measuring the concentration of iv injected Evans blue dye in eluates of sections of peritoneum and contiguous underlying tissue removed 3 hours after injection of dye. Permeability averaged 1.5 times normal (P = 0.02) by day 3 after tumor cell injection, 2 times normal by day 5, and 3 times normal by day 7; it remained at the final level. Although lymph drainage became impaired within 24 hours of the detection of ascites, a progressive increase in capillary permeability began 2 days earlier and was probably the predominant alteration in pathogenesis of the effusion.

Animals↗
PubMed2004

The albumin controversy.

There are relatively few studies of albumin use in neonates and children, with most showing no consistent benefit compared with the use of crystalloid solutions. Certainly, albumin treatment is not indicated for treatment of hypoalbuminemia alone. Studies also show that albumin is not indicated in neonates for the initial treatment of hypotension, respiratory distress, or partial exchange transfusions. In adults, albumin is not considered to be the initial therapy for hypovolemia, burn injury, or nutritional supplementation. Based on the evidence, albumin should be used rarely in the neonatal ICU. Albumin may be indicated in the treatment of hypovolemia only after crystalloid infusion has failed. In patients with acute hemorrhagic shock, albumin may be used with crystalloids when blood products are not available immediately. Inpatients with acute or continuing losses of albumin and normal capillary permeability and lymphatic function, such as during persistent thoracostomy tube or surgical site drainage, albumin supplementation will prevent the development of hypoalbuminemia, and possibly edema formation. This has not been studied systematically, however. In patients with hypoalbuminemia and increased capillary permeability, albumin supplementation often leads to greater albumin leakage across the capillary membrane, contributing to edema formation without improvement in outcome. As the disease process improves and capillary permeability normalizes, albumin supplementation may accelerate recovery, but long-term benefits of albumin treatment usually cannot be demonstrated. These patients will recover whether or not albumin is administered.

Albumins↗
PubMed1984

Effect of endotoxin on lung fluid balance in unanesthetized sheep.

We used a gravimetric technique to test for increased pulmonary capillary permeability after Escherichia coli endotoxin infusion in unanesthetized sheep. The sheep were chronically prepared with cannulas placed into the left atrium and pulmonary artery 1-2 wk before the experiments. We estimated pulmonary capillary pressure (Pc) as the average of pulmonary arterial and left atrial pressures, and used the modified method of Pierce to estimate the ratio of extravascular fluid weight (EVF) to blood-free dry weight. In 15 sheep we inflated a left atrial balloon to raise Pc to -10.7, 5, 10, or 15 mmHg above plasma oncotic pressure (IIc) for 3 h, then measured EVF. EVF averaged 4.0 +/- 0.2 (base line), 4.3 +/- 0.1, 4.5 +/- 0.1, and 5.1 +/- 0.5 (SD), respectively, for the four levels of Pc - IIc. We gave seven additional sheep 1 microgram/kg of E. coli endotoxin (0127:B8) and measured EVF after 3 h of stable Pc. Endotoxin increased Pc in each sheep. EVF was higher than control for the endotoxin sheep with Pc - IIc greater than -1. This finding is consistent with an increase in pulmonary capillary permeability caused by endotoxin. However, EVF was not elevated in the endotoxin sheep with Pc - IIc less than 1 mmHg. This shows that the increased permeability was insufficient to cause edema unless Pc was elevated. Thus endotoxin may cause edema by two mechanisms, 1) an increase in capillary permeability, and 2) an increase in Pc.

Animals↗
PubMedDate not supplied

Anti-allergic effects of ketanserin on animal models of allergic reactions.

The aim of the present study is to investigate the effect of ketanserin, a potent and selective S2-serotonergic antagonist, on some anaphylactic reactions in mice, rats and guinea-pigs. Ketanserin (1 and 5 mg/kg) inhibited both IgE antibody-mediated 48 hr homologous passive cutaneous anaphylaxis and IgG antibody-mediated 1.5 hr homologous passive cutaneous anaphylaxis in mice. In histamine-, serotonin- and LTC4-induced skin reactions in mice, ketanserin inhibited an increase of capillary permeability caused by each mediator. Cyproheptadine, at doses of 0.1 and 0.5 mg/kg, inhibits 48 hr and 1.5 hr homologous passive cutaneous anaphylaxis and histamine-induced capillary permeability increase in mice ear. The inhibitory activity of cyproheptadine on these reactions is more potent than that of ketanserin. However, ketanserin showed a more potent inhibition than cyproheptadine for serotonin-induced capillary permeability. In rat passive peritoneal anaphylaxis, ketanserin had little effect on the release of histamine from peritoneal mast cells. Ketanserin inhibited an antigen-induced contraction of the sensitized guinea-pig trachea at an early period (within 5 min after treatment with antigen) but not at a late period (between 5 to 15 min). Cyproheptadine had little effect on this antigen-induced contraction of sensitized guinea-pig trachea. Moreover, ketanserin inhibited both histamine- and serotonin-induced contractions of the guinea-pig trachea, but not the contraction caused by carbachol and LTC4. When Forssman antibody was injected into the guinea-pigs, a biphasic increase of airway resistance was observed. Ketanserin inhibited an increase of airway resistance at late phases. These results suggest that ketanserin inhibited some anaphylactic reactions in mice and guinea-pigs probably due to the antagonistic action of histamine and serotonin.

Airway Resistance↗
PubMedDate not supplied

Osmotic pressure of the serum proteins.

The osmotic pressure of the serum proteins (colloid osmotic pressure [COP] or "oncotic" pressure) is only one of the four Starling forces (plus the capillary permeability coefficient) which affect the net filtration of fluid from the capillaries. The COP will vary with the concentration of total serum proteins, but more so with the specific pattern or composition of the protein components, especially albumin. The use of formulas utilizing total protein (or albumin/globulin) to calculate COP is not warranted. COP should be determined; this is easy at the present time with the advent of a compact commercial instrument. Generalized or localized edema (e.g., pulmonary edema or ascites) has been associated with low serum albumin and low COP values. This is not always so since cases of analbuminemia do not necessarily exhibit edema. The study of COP is warranted but precautions are necessary in proper interpretation of the causes of "edema,"--the Starling forces and hemodynamic factors, capillary permeability, lymphatic return, etc., are all involved in the phenomenon.

Ascites↗
PubMed1987

Production of 5-lipoxygenase pathway metabolites by peripheral leucocytes in capillary leak syndrome (Clarkson disease).

Periodic systemic capillary leak syndrome (Clarkson disease) is characterized by unexplained attacks of a marked increase in capillary permeability. As leukotrienes, derived from arachidonic acid via the 5-lipoxygenase pathway, enhance capillary permeability, we studied arachidonate metabolism in leucocytes of a patient with capillary leak syndrome. Leucocyte-platelet suspensions, prepared from blood collected from the patient during asymptomatic periods (n = 11) produced greater amounts of 5-hydroxyeicosatetraenoic acid (5-HETE) than control suspensions (P less than 0.05). Peripheral leucocytes, collected during attacks (n = 3) and studied without addition of A23187 released LTB4 in vitro but not sulphidopeptides leukotrienes. This result was never observed with leucocytes from control subjects or from the patient out of a crisis. These results suggest that in the patient, peripheral leucocytes could be stimulated by an unknown, as yet to be determined, endogenous factor to produce more 5-HETE and LTB4. Whether LTB4 plays a pathogenic role in the capillary leakage remains to be determined.

Adult↗
PubMed2002

A dynamic shift of VEGF isoforms with a transient and selective progesterone-induced expression of VEGF189 regulates angiogenesis and vascular permeability in human uterus.

A key mechanism underlying physiological angiogenesis of the human endometrium is its ability to regenerate the vascular capillary network and to perform vascular remodeling (i.e., development of spiral arteries). Vascular endothelial growth factor (VEGF) is associated with angiogenesis and capillary permeability in this tissue. VEGF is expressed as several spliced variants, its main human isoforms contain 121 and 165 aa; 17beta-estradiol (E(2)) increases endometrial VEGF, possibly in all isoforms. Here we show that progesterone (P) selectively increases the expression of the VEGF(189) (V(189)) isoform in the human uterus. V(189) is identified in the conditioned medium of stromal cells treated with E(2) + P; its presence in this in vitro model of decidual stromal cells is detected after 6-8 days, using ELISA, and after 8-10 days, using Western blot analysis with different antibodies, including one specific for V(189). The secretion pattern of V(189) parallels that of the decidual protein IGFBP-1. V(189) is secreted as a native isoform, as compared with the migration of recombinant V(189) by SDS/PAGE. In situ hybridization and immunocytochemistry(,) performed on the same biopsies, suggest that decidual cells express V(189) during the mid-late secretory phase of the menstrual cycle and early gestation. Finally, using an in vivo permeability assay, we show that native V(189) increases capillary permeability. These observations demonstrate that P regulates V(189) expression in decidual cells, which could have important implications for understanding uterine vascular remodeling and implantation, and may be relevant in a range of disease states such as edema and irregular bleeding.

Capillary Permeability↗
PubMed1997

Acute pancreatitis in rats: effects of sodium taurocholate, CCK-8, and Sec on pancreatic microcirculation.

With use of in vivo microscopy, pancreatic duct permeability, red blood cell (RBC) velocities, functional capillary density (FCD), and overall changes in capillary blood flow (perfusion index) were estimated after intraductal infusion of sodium taurocholate (0.8 ml, 4%) alone or in combination with systemic administration of cholecystokinin (CCK, 0.3 microg/100 g body wt) or secretin (Sec, 10 microg/100 g body wt). Sodium taurocholate mediated a significant increase in pancreatic duct and capillary permeability within 105 +/- 26 s followed by a transient decrease in RBC velocities and a sustained decrease in FCD, which were paralleled by dramatic flow heterogeneity. Therefore, a significant reduction in overall capillary blood flow was calculated. CCK stimulation aggravated the microcirculatory failure due to a decrease in RBC velocities, which was accompanied by an increase in acinar cellular necrosis. Sec stimulation attenuated microcirculatory failure due to a more moderate reduction of FCD. The enhanced pancreatic duct and capillary permeability, which enables free diffusion of pancreatic digestive enzymes into the parenchyma, is the initiating event in acute biliary pancreatitis, causing microcirculatory failure and tissue damage. The microcirculatory changes are secondary and a propagating factor for the development of acini necrosis. Stimulation with CCK worsened the course of acute biliary pancreatitis.

Acute Disease↗
PubMed2001

Glomerular permeability after surgical trauma in children: relationship between microalbuminuria and surgical stress score.

OBJECTIVES: To determine whether there is an increase of urinary albumin during and after surgical trauma and investigate a possible relationship between microalbuminuria and the severity of surgical stress. DESIGN: Prospective study. SETTING: University hospital pediatric intensive care unit. PATIENTS: Forty consecutive children scheduled for elective surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Microalbuminuria/urinary creatinine ratio (MACR) was measured before, during, and after elective moderate or major surgical procedures. The Oxford Surgical Stress Score (SSS) was determined for each patient at the end of the operation, and its relationship with maximum deviation of MACR from baseline values was investigated. MACR showed a progressive increase during surgery and a decrease afterward, reaching preoperative values in most cases within 24 hrs after the end of surgery. There was a significant correlation between the increase in MACR and severity of the surgical trauma as measured by SSS. Two patients showed a rise in MACR after the initial postoperative normalization before clinical appearance of a surgical complication and one patient showed a persistent rise in MACR before clinical appearance of a septic complication. None of the other patients showed any rise in MACR after postoperative normalization, and they all had an uneventful recovery. CONCLUSIONS: MACR rises during and after major or moderate elective surgery in children. There is a significant positive correlation between severity of surgical trauma and capillary permeability in pediatric patients. Microalbuminuria, as an index of capillary permeability, may be an early sign of incipient complications and assist in the identification of those patients whose condition will deteriorate. The test is a cheap, blood-sparing, easy-to-perform bedside procedure that may have a useful role in clinical practice for evaluating the effect of surgical trauma on capillary permeability in children.

Albuminuria↗