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PubMed2003

Anti-inflammatory activity of 3-benzoyl-1-methyl-4-phenyl-4-piperidinol hydrochloride.

In our study, the effects of the compound 3-benzoyl-1-methyl-4-phenyl-4-piperidinol hydrochloride (C1) and also an anti-inflammatory drug, indomethacin, tested by carrageenan-induced paw edema and cotton pellet granuloma tests, for their effects on acute and chronic phases of inflammation, respectively. Their effects on vascular permeability were also tested by hyaluronidase-induced capillary permeability. C1 decreased the carrageenan-induced paw edema 61.98, 80.84, and 90.32% at 50, 100, and 200mgkg(-1) doses, respectively, while this decrease was 89.93% by indomethacin at 20mgkg(-1) dose. Antiproliferative effects of C1 at 100mgkg(-1) and indomethacinin at 20mgkg(-1) doses were 46.1 and 43.1%, respectively, in cotton pellet test. C1 and indomethacin both significantly inhibited the hyaluronidase-induced increase in capillary permeability.

Analysis of Variance↗
PubMed1986

MR evaluation of pulmonary interstitial and intravascular fluids.

Serial dilutions of sheep plasma and red blood cells were made yielding blood samples of various hematocrits (Hcts). These samples were studied at bore temperature (34 degrees C) in a 0.25 T pulsed NMR analyzer for differences in T1 and T2. An inverse relationship between Hct and T1 was demonstrated (P less than .001); no change was detected in T2 with Hcts from 0% to 88%. Plasma and lung lymph samples were also obtained from chronically instrumented, unanesthetized sheep to determine the effects on T1 and T2 of increasing hydrostatic pressure and altering capillary permeability in the lungs. Normal baseline lung lymph T1 was longer than the concurrent plasma T1. T1 of lung lymph was inversely proportional to the lymph/plasma protein ratio. Edema induced by elevation of hydrostatic pressure lengthens T1, whereas increased capillary permeability shortens T1. T2s were unchanged in plasma and lymph in the baseline state with hydrostatic edema, and with increased capillary permeability.

Animals↗
PubMed1988

Ovarian hyperstimulation syndrome. A case history and review.

For the past two decades, significant advances have been made in the treatment of anovulation. The use of therapeutic agents for induction of ovulation, however, has given rise to several adverse reactions, the most important and serious of such complications being the ovarian hyperstimulation syndrome (OHSS), which can be fatal. It is characterized by gross ovarian enlargement, ascites, pleural effusion, hemoconcentration and thromboembolic disorder, which are potentially lethal conditions. The main pathogenic mechanism is considered to be increased capillary permeability, especially of the ovarian vessels, causing acute body fluid shift from the intravascular compartment to the peritoneal and pleural cavities. An experimental model of OHSS suggests that prostaglandins mediate this increased capillary permeability and transudation. Management is based on the concept of the pathogenic mechanism and includes maintenance of intravascular volume by plasma volume expanders, reduction of capillary permeability and prevention of thromboembolic complications. Surgical intervention is indicated only in cases of ovarian torsion or rupture and should be as conservative as possible.

Adult↗
PubMed1999

Randomized trial of hydroxyethyl starch versus gelatine for trauma resuscitation.

BACKGROUND: Previous studies have demonstrated the rapid increase in systemic capillary permeability after blunt trauma and its association with poor outcome. There are theoretical advantages in resuscitation with colloid fluids, which are well retained in the vascular compartment during times of capillary leak. The aim of this study was to compare the effects of posttrauma resuscitation with hydroxyethyl starch (HES) (molecular mass, 250 kDa) or gelatine (molecular mass, 30 kDa), the hypothesis being that HES would reduce capillary leak. METHODS: Forty-five patients suffering blunt trauma were randomized on admission to receive either gelatine (Gelofusine) (n = 21) or HES (Pentaspan) (n = 24) for the first 24 hours, after which the choice of fluid was at the discretion of the clinician. The mean Injury Severity Score for the HES and gelatine groups were 20.0 (range, 9-41) and 18.1 (range, 9-32), respectively (p = 0.43). Capillary permeability was assessed by urine albumin excretion rate for the first 24 hours. For 5 days the daily mean P(O2)/F(IO2) ratio, serum C-reactive protein, hemoglobin, white cell and platelet counts, prothrombin, and activated partial thromboplastin time were recorded. RESULTS: Capillary permeability was lower in HES-treated patients during the first 24 hours. Log mean (95% confidence interval) albumin excretion rate for gelatine and HES groups at 6 hours were 117.5 (84.9) and 46.8 (24.3) microg/min (p = 0.011), at 12 hours were 54.9 (30.0) and 17.2 (7.6) microg/min (p = 0.001), and at 24 hours were 50.5 (23.4) and 23.6 (16.3) microg/min (p = 0.030), respectively. The mean (95% confidence interval) P(O2)/F(IO2) ratio for the HES and gelatine groups 48 hours after admission were 324 (44) and 267 (43) mm Hg, respectively (p = 0.03). The mean (95% confidence interval) serum C-reactive protein in the HES and gelatine groups 24 hours after admission were 72.4 (19.2) and 105.7 (30.1) mg/L, respectively (p = 0.03). There were no significant differences in any of the hematologic parameters during the first 48 hours. CONCLUSION: The results suggest that compared with gelatine, resuscitation with HES reduces posttrauma capillary leak.

Adolescent↗
PubMedDate not supplied

Therapy for microcirculatory disorders in severe acute pancreatitis: effectiveness of platelet-activating factor receptor blockade vs. endothelin receptor blockade.

Many of the complications of severe acute pancreatitis are the result of the amplifying effects of microcirculatory disruption. The factors causing microcirculatory disorders in acute pancreatitis involve vasoactive mediators such as platelet-activating factor (PAF) and endothelin-1 (ET) activated during the inflammatory response to pancreatic injury. To further evaluate the potential therapeutic role of specific receptor antagonists (RA) to these mediators, the present study compares the effect of PAF and ET receptor blockade on microcirculation and organ function in a well-established rodent model of severe acute pancreatitis. Six hours after acute pancreatitis induction, rats were randomized to therapy with ET-RA (50 mg/kg LU-135252), PAF-RA (82 microg/kg WEB-2170), or NaCl 0.9% (volume equivalent). After 18 hours of fluid resuscitation, animals were relaparotomized for intravital microscopic determination of capillary blood flow, leukocyte rolling, and capillary permeability in the pancreas and colon. Other measurements included cardiorespiratory parameters, hematocrit, pleural effusions, ascites, urine production, and survival. Compared to saline treatment both ET-RA and PAF-RA significantly improved capillary blood flow in the pancreas and colon, reduced leukocyte rolling, and stabilized capillary permeability. The beneficial effects of receptor antagonist treatment on microcirculation were associated with decreased fluid loss into the third space, improved renal and respiratory function, and survival. Although both receptor antagonists likewise improved capillary blood flow, ET-RA was significantly more effective in counteracting leukocyte rolling and capillary leakage, thereby further reducing fluid sequestration. The present study confirms the beneficial effects of PAf and ET receptor blockade on microcirculation inside and outside the pancreas, organ function, and survival when given at the early stage of severe pancreatitis. Because ET-RA was more effective in stabilizing capillary permeability and avoiding subsequent fluid loss into the third space, we propose that ET-RA should be tested in a clinical trial (either in comparison or in addition to PAF-RA).

Animals↗
PubMed1995

Advances in understanding permeability in fetal capillaries of the human placenta: a review of organization of the endothelial paracellular clefts and their junctional complexes.

A review is presented of the evidence that the capillaries of the fetal-placental circulations of man and the guinea-pig are typical members of class of continuous non-brain capillaries. Their permeability is similar to that of muscle capillaries, and there is much evidence that the main permeation route for hydrophilic solutes in capillaries of this class is through the paracellular clefts of the endothelium. The properties of this paracellular route are based on discontinuous tight junctions which may serve to restrict the fraction of the paracellular cleft available to solutes, and on a molecular sieve which may be based on arrays of adhesion molecules in the zonula adhaerens of the junctional complex. The characteristics of this paracellular route and of overall microvascular permeability in these types of placenta make it clear that fetal capillaries form a significant component of the total transplacental permeability restriction.

Animals↗
PubMed1978

Pulmonary capillary and permeability during hemorrhagic shock.

In previous experiments from this laboratory horseradish peroxidase was used to study the structural and functional characteristics of the normal canine pulmonary capillary membrane. The present study used the same technique to try to determine if any change occurred in the pulmonary capillary as a result of hemorrhagic shock. We found that hemorrhagic shock caused a fall (5 expt) or no change (2 expt) in estimated pulmonary transcapillary pressure based on Starling's equation. However, lymphatic flow from the lungs increased. Estimated of filtration coefficients showed a highly significant increase (P less than 0.01) during the hypotensive period. Pulmonary lymphatic protein concentrations were not altered, indicating that water and protein continued to traverse the membrane in the same proportions as under normotensive conditions. These data are consistent with recent observations of minimal changes in the intercellular junctions of the capillary endothelium following hemorrhagic shock made independently on lung tissue from these experiments.

Animals↗
PubMed1997

[Double isotope albumin flux measurement: diagnosis and therapeutic monitoring of acute lung injury].

PURPOSE: Acute Lung Injury (ALI) is a clinical condition which is associated with a high lethality. It is characterized by an increased pulmonary capillary permeability and non-cardiogenic pulmonary edema. This study was designed to answer the question whether double isotope albumin-flux measurement is a useful tool both for diagnosis of increased pulmonary capillary permeability and for monitoring therapeutic interventions (nitric oxide (NO) inhalation). METHOD: In 12 patients with clinical signs of ALI, transvascular albumin-flux was measured by a double radioisotope technique before, during and after NO inhalation. 99mTc labeled albumin and 51Cr labeled autologous erythrocytes were used as tracer. The radioactivity of both radiopharmaceuticals was measured externally over the right lung by a radiation probe and simultaneously in arterial blood. For quantification of transvascular albumin-flux Normalized Index (NI) and Normalized Slope Index (NSI) were calculated. Furthermore, pulmonal vascular pressures and other physiological parameters were recorded. RESULTS: All 12 patients showed markedly increased NSI before inhalation of NO. NSI decreased from 0.0074 +/- 0.0046 min-1 without nitric oxide to -0.0051 +/- 0.0041 min-1 during nitric oxide and increased to 0.0046 +/- 0.0111 min-1 after nitric oxide. The decrease of the NSI correlated well with decrease of venous pulmonary resistance during inhalation of NO. CONCLUSION: Inhalation of NO reduces transvascular albumin-flux in patients with ALI. Double isotope albumin-flux measurement enables diagnosis of increased capillary permeability as well as monitoring therapeutic interventions.

Adult↗
PubMed1986

Unexplained acute membrane pulmonary oedema related to anaesthesia.

Five patients developed severe pulmonary oedema in relationship to elective anaesthesia and surgery. The oedema was due to increased capillary permeability in four patients and probably due to increased capillary permeability in the other. No cause could be found in any patient.

Acute Disease↗
PubMed1995

Platelet-activating factor increases vascular resistance in rat hindquarters by thromboxane A2.

The effects of platelet-activating factor (PAF) on vascular resistance and capillary permeability were studied in the isolated rat hindquarter. Six groups were studied (n = 30): control; PAF alone (1.4 microM); and PAF (1.4 microM) pretreated with ibuprofen (30 mg/kg), thromboxane A2 (TxA2)-receptor antagonist (BM-13505, 2 mg/kg), PAF-receptor antagonist (WEB-2086, 5 mg/kg), or dexamethasone (5 mg/kg). The vascular resistance was calculated, and the reflection coefficient (sigma) was determined as an index of capillary permeability. Exogenous PAF caused a threefold increase in vascular resistance peaking at 5 min and a 2.5-fold increase in capillary permeability. The increased vascular resistance caused by PAF alone was significantly attenuated by ibuprofen, BM-13505, and dexamethasone. The PAF-induced permeability was neither attenuated by ibuprofen nor BM-13505. However, both the increased vascular resistance and permeability were blocked and attenuated by WEB-2086 and dexamethasone, respectively. We conclude that TxA2 mediates the PAF-induced increased vascular resistance; however, the increased vascular permeability is independent of the formation of TxA2 in the isolated hindquarter.

Animals↗
PubMed1987

Selective availability of protein bound estrogen and estrogen conjugates to the rat kidney.

Estrogen glucuronides are selectively cleared by the kidney as compared to estrogen sulfates. The selective trafficking of circulating serum estrogen conjugates to kidney and urine may arise from differential transport properties of the various estrogen conjugates in the renal microcirculation. In the present study, the effects of glomerular and peritubular permeability barriers, and plasma protein binding on the influx of unconjugated and conjugated estrogens into rat kidney were studied. Experiments were carried out utilizing an in vivo double isotope, single injection, timed tissue sampling technique. The extractions of these steroids by the renal cortex were examined utilizing inulin as the reference substance, as it is freely permeable through the glomerular and tubular capillary permeability barriers, but not extracted by tubular epithelial cells. The method was validated by studying the extraction of para-amino hippuric acid (PAH) before and after probenecid treatment. In the absence of plasma proteins, all the estrogens and estrogen conjugates readily diffused through both the glomerular and peritubular capillary permeability barriers and were extracted by tubular epithelia. The addition of 4% albumin to the injection solution led to significant inhibitions of extraction of estradiol (E2) and estrone sulphate (E1-S) only. The extraction of E1-S was reduced to a value less than that of inulin; the extraction of E2 was less than that of control value but significantly more than that of inulin. The addition to the injection solution of human pregnancy sera containing sex hormone binding globulin and albumin was associated with a reduction in the extraction of all estrogens and estrogen conjugates except estriol and E1-S to values approximating that of inulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Low-power Helium-Neon laser irradiation enhances the expression of VEGF in murine myocardium.

BACKGROUND: Low-power helium-neon (He-Ne) lasers have been increasingly widely applied in the treatment of cardiovascular diseases, and its vasodilation effect has been proven. The aim of this study was to determine the effects of low-power He-Ne laser irradiation directed at the precardial region of Wistar rats on capillary permeability in the myocardium and the expression of myocardial vascular endothelial growth factor (VEGF). METHODS: Sixteen rats were divided randomly into control and irradiated groups (n = 8, each). A He-Ne laser (632.8 nm) was applied to the irradiated group with a dose of 60.5 J/cm(2). Ferritin was perfused into the left femoral vein and capillary permeability was examined under an electron microscope. VEGF expression in the myocardium was investigated by immunohistochemical methods, RT-PCR, and image analysis. RESULTS: The ultrastructures of the myocardial capillaries were examined. Compared to the control group, more high-density granules (ferritin), which were present within the capillary endothelium and the mitochondrions of myocardial cells in the internal layer of the myocardium, were observed in the irradiated group. VEGF staining of the myocardium was stronger in the irradiated group than that in the control group. The optic density of the irradiated group (0.246 +/- 0.015) was significantly higher than that of the control group (0.218 +/- 0.012, P < 0.05). Finally, the levels of RT-PCR products of VEGF165 mRNA were 2.79 times higher in irradiated rats than in the control rats. CONCLUSIONS: Our study demonstrates that He-Ne laser irradiation (in doses of 60.5 J/cm(2)) increases myocardial capillary permeability and the production of VEGF in myocardial microvessels and in myocardium. Our study provides experimental morphological evidence that myocardial microcirculation can be improved using He-Ne laser irradiation.

Animals↗
PubMed1990

Lung microvascular transport properties measured by multiple indicator dilution methods in patients with adult respiratory distress syndrome. A comparison between patients reversing respiratory failure and those failing to reverse.

We conducted indicator dilution studies on the lungs of patients in the early phases of adult respiratory distress syndrome (ARDS) to test the hypothesis that capillary permeability was increased in patients with respiratory failure. Indicator dilution studies were performed using 51Cr-erythrocytes, 125I-albumin, 14C-urea, and 3H-water as tracers. The injectate was infused as a bolus into a central venous line. Peripheral arterial blood was collected and counted for radioactivity. Mathematical analysis of the indicator curves yielded cardiac output, measures of the product of capillary permeability and surface area for urea (PS and D1/2S), the intravascular lung volume (Vv), and the extravascular lung water volume (Ve). Permeability was separated from surface area by normalizing PS and D1/2S to Vv. Patients could be divided into 16 in whom blood gas determinations and radiologic criteria for ARDS were reversed and 23 in whom they were not. We examined indicator dilution and other measures of lung function in the two groups to determine whether significant differences in microvascular function existed. PS and PS/Vv were significantly higher in the nonreversal patients. Ve was above normal, but not different between groups. Linear regression analysis showed significant correlations for all of the following in the nonreversal group: Ve and all measures of permeability, pulmonary vascular resistance (PVR), and the inverse of permeability-surface area measures and AaDO2 and PVR. Only measures of Ve and PS correlated in the reversal group. These results support the hypothesis that capillary permeability is increased in patients with early ARDS and continuing respiratory failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗
PubMed1996

[Antioxidant action of Foy in an experimental model of hypergeneration of oxygen free radicals].

BACKGROUND: Several trials have just demonstrated the therapeutic efficacy of gabexate mesylate (Foy). For this drug numerous mechanisms of action have been postulated; protease inhibition, direct or indirect lysosomal membrane stabilization, etc. The aim of this study has been to verify if Foy would express antioxidant properties against free radical overgeneration, responsible for the increase in microvascular permeability which represents one of the most important pathogenetic phenomenon of any condition of shock. A mixture of hypoxanthine-xanthine oxidase has been used to obtain a generation of oxygen free radicals in vivo. METHODS: Experiments were performed on the mesocecum of male Wistar rats; fluorescent labelled bovine albumin has been injected intra-arterially to evaluate the capillary permeability and the mesocecum microcirculation has been observed by fluorescent microscopy. The control group received saline i.v., the second group received topically applied on the mesocecum a mixture of 0.96 mM hypoxanthine and 0.05 UI/ml xanthine oxidase; the third and the fourth groups were pretreated respectively with a topical application and continuous infusion of a Foy 1% solution (50 ml/kg/min). To evaluate capillary permeability and to quantify the degree of extravasation by counting the number of leaky sites, labelled bovine albumin was injected i.a. and mesocecum was observed with fluorescent microscopy for 2 hours. RESULTS AND CONCLUSION: Gabexate mesilate (Foy) exerts its efficacy preventing the increase in capillary permeability provoked by an overgeneration of free radicals; it could express antioxidant properties.

Animals↗
PubMed1969

Intestinal capillaries. I. Permeability to peroxidase and ferritin.

Horseradish peroxidase (mol. diam. approximately 50 A) and ferritin (mol. diam. approximately 110 A) were used as probe molecules for the small and large pore system, respectively, in blood capillaries of the intestinal mucosa of the mouse. Peroxidase distribution was followed in time, after intravenous injection, by applying the Graham-Karnovsky histochemical procedure to aldehyde-fixed specimens. The tracer was found to leave the plasma rapidly and to reach the pericapillary spaces 1 min post injection. Between 1 min and 1 min 30 sec, gradients of peroxidase reaction product could be demonstrated regularly around the capillaries; their highs were located opposite the fenestrated parts of the endothelium. These gradients were replaced by even distribution past 1 min 30 sec. Ferritin, followed directly by electron microscopy, appeared in the pericapillary spaces 3-4 min after i.v. injection. Like peroxidase, it initially produced transient gradients with highs opposite the fenestrated parts of the endothelium. For both tracers, there was no evidence of movement through intercellular junctions, and transport by plasmalemmal vesicles appeared less efficient than outflow through fenestrae. It is concluded that, in the blood capillaries of the inintestinal mucosa, the diaphragms of the endothelial fenestrae contain the structural equivalents of the small pore system. The large pore system seems to be restricted to a fraction of the fenestral population which presumably consists of diaphragm-free or diaphragm-deficient units.

Animals↗
PubMedDate not supplied

Assessment of pulmonary vascular injury.

The assessment of pulmonary injury in experimental and clinical situations remains a challenge. A method of quantifying pulmonary vascular aberrations in animal models and human clinical situations is described. A multiple-indicator dilution technique is employed to assess changes in lung capillary permeability--surface area product, extravascular lung water, and cardiac output. A mixture of 51Cr-RBC, 125I-albumin, tritiated water, and [14C]urea is injected into a central vein. Samples of the subject's blood are collected at timed intervals and counted for beta and gamma activity. Time concentration curves for each isotope are constructed. The capillary permeability--surface area product is calculated from the extraction pattern for [14C]urea. Extravascular lung water is calculated from the extraction pattern of tritiated water and cardiac output is calculated from the inverse of the area under the 51Cr curve. Normal reference curves are constructed for all subject groups. Significant changes occurred in capillary-permeability surface area product and extravascular lung water in various experimental models producing injury, in the patient population manifesting adult respiratory distress syndrome, and in those patients who have received cardiopulmonary transplants. The multiple-indicator dilution technique represents a sensitive tool for evaluating pulmonary vascular changes.

Animals↗