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PubMed2000

Effects of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine on the blood-brain barrier permeability in the rat.

Histamine plays a role in the regulation of the blood-brain barrier function. In this study, effects of N, N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine (DPPE), an intracellular histamine binding site antagonist on the cerebrovascular permeability were investigated in control and post-ischemic male Wistar rats. Intravenous administration of DPPE, in a dose of 1 and 5 mg/kg, was not followed by any major clinical change, but 20 mg/kg proved to be toxic. A significantly (P<0.05) increased permeability for sodium fluorescein (MW=376) was seen in hippocampus, striatum, and cerebellum, but not in parietal cortex, of rats 2 h after the injection of 5 mg/kg DPPE, whereas no increase was measured later. There was a more intense (5- to 12-fold) and prolonged elevation in Evan's blue-labeled albumin (MW=67,000) extravasation 2, 4, and 8 h after 5 mg/kg DPPE administration in each brain region. In parietal cortex, a dose-dependent increase in albumin extravasation developed 4 h after intravenous injection of 1, 5, and 20 mg/kg DPPE, but doses applied resulted in no significant change in sodium fluorescein permeability. Cerebral ischemia-reperfusion evoked by four-vessel occlusion caused a significant (P<0.05) increase in the permeability for albumin in each region, but few changes in that of sodium fluorescein. DPPE treatment failed to prevent the ischemia-reperfusion-induced changes in the blood-brain barrier permeability. In conclusion, DPPE induced an increased permeability in the rat, which supports a role for histamine, as an intracellular messenger, in the regulation of the blood-brain barrier characteristics.

Animals↗
PubMed2002

Akt signaling mediates VEGF/VPF vascular permeability in vivo.

VEGF is an endothelial cell cytokine that promotes angiogenesis and enhances microvascular permeability. Recently, it has been shown that the protein kinase Akt functions in a key intercellular signaling pathway downstream of VEGF. Here, we employed adenovirus-mediated gene transfer in conjunction with the Miles assay in hairless albino guinea pigs to assess the role of Akt signaling in vascular permeability. VEGF-induced vascular permeability was blocked by the transduction of a dominant negative mutant of Akt. Conversely, transduction of a constitutively active form of Akt promoted vascular permeability in a manner similar to VEGF protein administration. This Akt-mediated increase in vascular permeability was inhibited by the eNOS inhibitor L-NAME. These data show that Akt signaling is both necessary and sufficient for vascular permeability in an in vivo model.

Animals↗
PubMed1988

The chemotactic peptide N-formyl methionyl-leucyl-phenylalanine increases mucosal permeability in the distal ileum of the rat.

Activation of granulocytes within the lamina propria by luminally derived bacterial products may represent an important mechanism in the pathogenesis of inflammatory bowel disease. The objective of this study was to determine the effects of luminal perfusion with N-formyl methionyl-leucyl-phenylalanine (FMLP), a bacterial product that attracts and activates granulocytes, on mucosal permeability in different regions of the rat small intestine and colon. Mucosal permeability was measured using blood-to-lumen clearance of 51Cr-ethylenediamine-tetraacetate during luminal perfusion with FMLP (10(-3) to 10(-8) M) dissolved in Tyrode's solution. Of the bowel segments studied, mucosal permeability was significantly increased by FMLP only in the distal 10 cm of ileum. The minimal FMLP concentration required to increase mucosal permeability was 10(-6) M. The increased mucosal permeability induced by FMLP could be prevented by depletion of circulating granulocytes with antineutrophil serum. The greater sensitivity of the distal ileum to FMLP did not correlate with a higher tissue myeloperoxidase activity, but it was associated with a higher basal ethylenediaminetetraacetate clearance. These observations indicate that a high basal mucosal permeability to solutes the size of FMLP (5-6 A radius), rather than a greater number of resident granulocytes in the lamina propria, predisposes the terminal ileum to the inflammatory actions of FMLP.

Animals↗
PubMed1993

Mucosal permeability in the immature rat intestine: effects of ischemia-reperfusion, cold stress, hypoxia, and drugs.

Increased mucosal permeability may represent an important factor in the etiology of necrotizing enterocolitis (NEC). In the present study we used an immature rat model to assess the permeability effects of a number of stresses commonly seen in infants with NEC. In 10-day-old rats, mucosal permeability to 51Cr EDTA was measured after subjecting the animals to 10-minute ischemia-reperfusion injury, 30 minutes of hypoxia (14% oxygen), cold stress (4 degree C for 4 minutes), and intraperitoneal indomethacin (0.2 or 2.0 mg/kg) or theophylline (40 or 200 mg/kg). When compared with appropriate controls, mucosal permeability was found to be significantly increased by ischemia-reperfusion injury, hypoxia, and high-dose indomethacin, but not by cold, theophylline, or low-dose indomethacin. Renal clearance studies confirmed that elevated blood levels of 51Cr EDTA were due to increased permeability rather than decreased renal excretion of the probe. These studies confirm that mucosal permeability in the immature rat is increased by a variety of insults, and may represent a "common pathway" in the etiology of NEC.

Animals↗
PubMed1996

Testicular vascular permeability: effects of experimental lesions associated with impaired testis function.

PURPOSE: Pathologies like varicocele and testicular torsion are known to alter testicular blood flow, either acutely or chronically. The present study was undertaken to determine whether or not alterations in testicular vascular permeability accompany these changes in testicular blood flow. MATERIALS AND METHODS: Testicular vascular permeability was examined by determining the appearance of radiolabelled molecules (m.w. = 18 to 70,000) in testicular interstitial fluid after acute infusion into the proximal testicular artery of the rat. These vascular permeability studies were carried out in control animals, in those with 30 day experimental left varicocele (ELV), or in those having experienced a 1 hour, 720 degrees experimental torsion either 1 hour or 24 hours prior to the study. RESULTS: Experimental left varicocele did not alter vascular permeability to the molecules studied, but 1 hour torsion did cause a significant increase in vascular permeability within 24 hours after repair of the torsion. CONCLUSION: Alteration in vascular permeability is one of the family of events contributing to cell death after repair of experimental testicular torsion, but is not a factor in the pathobiology of experimental varicocele.

Animals↗
PubMed1997

Microvascular permeability with sulfonylureas in normal and diabetic hamsters.

The hamster cheek pouch is an experimental model in which quantitative studies of macromolecular permeability can be made by direct observation of extravasated fluorescein isothiocyanate (FITC)-dextran (leaks). The advantage of this model is that simultaneous light and fluorescent-light microscopy observations can be performed with instantaneous correlations between the site of FITC-dextran extravasation and the vessel morphology. The aims of our study were to compare, using the cheek pouch preparation, the effects of two sulfonylureas, gliclazide and glibenclamide, on the macromolecular permeability increase induced by histamine using control (normoglycemic) hamsters. In these studies, FITC-labeled dextran 150,000 daltons was administered intravenously and quantified by UV-light microscopy, and the drugs used were applied topically at therapeutic concentrations. Gliclazide and glibenclamide dose-dependently decreased the macromolecular permeability increase induced by histamine. This effect of gliclazide could be blocked by nifedipine (Ca2+ channel blocker) and not by diazoxide (K+ channel opener), whereas for glibenclamide it could be blocked by diazoxide and not by nifedipine. To better characterize the antioxidant capacity of gliclazide and glibenclamide, their effect on the macromolecular permeability increase induced by ischemia/reperfusion was also compared with the effect of vitamin C in diabetic hamsters (glycemia > 240 mg/dL). Total ischemia of the preparation was obtained with a cuff placed around the neck of the everted pouch. Diabetes was induced by three intraperitoneal injections of streptozotocin 50 mg/kg/d in 3 days. In diabetic hamsters during ischemia/reperfusion, gliclazide was more effective in inhibiting the macromolecular permeability increase than glibenclamide (136.0 +/- 5.8 leaks/cm2 for placebo; 68.0 +/- 2.9 for 1.2 x 10(-6) mol/L gliclazide; 55.3 +/- 3.5 for 1.2 x 10(-5) mol/L gliclazide; 89.2 +/- 5.7 for 8 x 10(-8) mol/L glibenclamide; 107.0 +/- 3.8 for 8 x 10(-7) mol/L glibenclamide; 56.7 +/- 3.4 for 10(-6) mol/L vitamin C; and 20.5 +/- 0.6 for 10(-5) mol/L vitamin C). Our results suggest that (1) the inhibition of the permeability increase induced by histamine elicited by gliclazide may be mediated by Ca2+ channels, while that of glibenclamide may be mediated by K+ channels, and (2) gliclazide appears to have an antioxidant capacity in ischemia/reperfusion injury similar to that of 10(-6) mol/L vitamin C. Improvement in the microcirculation was independent of the hypoglycemic properties of the drug.

Animals↗
PubMed2003

Inhibition of Rho kinase decreases hydraulic and protein microvascular permeability in cat skeletal muscle.

Rho-associated kinases are involved in regulation of actin-myosin contractility and the organization of the actin cytoskeleton in both endothelial and smooth muscle cells. By influencing the contraction of the intraendothelial filaments, Rho kinases may affect the size of the interendothelial gaps and thereby influence microvascular permeability. The aim of the study was therefore to investigate whether Rho kinases influence hydraulic and protein microvascular permeability. The study was performed on the autoperfused cat skeletal muscle. A capillary filtration coefficient (CFC) technique was used to evaluate changes in hydraulic permeability, and protein permeability was evaluated by estimation of the change in the reflection coefficient for albumin. In the first part of each experiment, the effects on CFC of three doses of the Rho kinase inhibitor Y-27632 of about 0.35, 0.70, and 1.05 microg/h per ml plasma flow were determined. There was a reduction in CFC at the lowest dose, and a tendency to further reduction at the higher doses used, reaching a decrease in CFC of 20%. The effects on CFC of the high and the middle dose did not differ. The reflection coefficient for albumin was increased by 31% following infusion of the highest dose of Y-27632. We conclude that hydraulic and protein microvascular permeability increase by Rho kinase activation, and that Rho kinase is involved in regulation of microvascular permeability.

Amides↗
PubMed1996

Increased intestinal permeability in bronchial asthma.

T lymphocytes are a major component of bronchial inflammatory processes in asthma. Because lymphocytes have the ability to migrate from one mucosal site to another, we initiated this prospective study to demonstrate mucosal abnormalities of the digestive barrier in asthma. To establish this we studied intestinal permeability in a group of 37 patients with asthma (21 allergic and 16 nonallergic) by measuring chromium 51-labeled ethylenediaminetetraacetatic acid (CrEDTA) urinary recovery. The results were compared with those obtained in a group of 13 nonasthmatic patients with chronic obstructive pulmonary disease and 26 healthy control subjects. Urinary recovery of CrEDTA was significantly higher in patients with asthma (2.5% +/- 1.95%) than in patients with chronic obstructive pulmonary disease (1.16% +/- 0.48%) and healthy control subjects (1.36% +/- 0.14%). There was no significant difference in intestinal permeability between patients with allergic asthma (2.94% +/- 2.4%) and those with nonallergic asthma (1.92% +/- 0.9%). Intestinal permeability was not correlated with the severity of asthma as measured by FEV1. Similarly, intestinal permeability did not significantly vary according to Aas score or steroid treatment. Serum IgE values and eosinophil blood count were not correlated with intestinal permeability. Intestinal permeability was evaluated sequentially in seven patients with asthma (4 allergic and 3 nonallergic) with a mean interval of 7.6 months (range, 2 to 13 months) and did not significantly change. Our results support the hypothesis that a general defect of the whole mucosal system is present as a cause or a consequence of bronchial asthma.

Adult↗
PubMed1984

Histamine increases lung permeability by an H2-receptor mechanism.

The effect of specific H1 and H2 receptor antagonists on bronchial reactivity and increase in lung epithelial permeability in response to inhaled histamine was measured in 5 non-smoking men (age range 24-36 years). Inhaled histamine produced a short-lived but consistent increase in permeability to 99Tc-diethylenetriamine penta-acetate. An H1-receptor antagonist, terfenadine (60 mg), protected against the bronchoconstrictor effect but had no significant influence on the increase in permeability. The H2-receptor antagonist ranitidine (150 mg) significantly reduced the permeability response without having an effect on bronchial reactivity. These results demonstrate that the bronchoconstrictor effect of histamine is mediated by H1 receptors and permeability increase is mediated by H2 receptors. H2-receptor mediated increase in lung epithelial permeability may be important clinically.

Adult↗
PubMed1982

Decreased endothelial permeability in the iridocorneal endothelial syndrome.

Five patients with the iridocorneal endothelial (ICE) syndrome were examined by fluorophotometry. All patients had typical abnormal corneal endothelium, peripheral anterior synechiae, and distortion of the iris (pupillary irregularity or anterior stromal traction tears) in one eye only. Fluorescein was deposited in the superior cornea of both eyes by iontophoresis, and the cornea and anterior chamber concentrations and total mass of fluorescein were measured hourly over the ensuing eight hours. In all five patients, the endothelial permeability to fluorescein was within normal limits in the normal eye. In four of the five abnormal eyes, endothelial permeability was markedly decreased. In these four patients, the permeability to fluorescein in the normal eye was approximately six times that in the abnormal eye. In the fifth patient, the endothelial permeability was normal in both eyes. The central corneal thicknesses were normal in both eyes of all five patients. These results indicate that in many eyes with the ICE syndrome, corneal endothelial permeability to solutes is markedly decreased. Decreased endothelial permeability to solutes has not been documented previously in any clinical corneal disorder and may be of importance in the pathophysiologic changes that accompany endothelial disease.

Adult↗
PubMed1992

Corneal epithelial permeability of dry eyes before and after treatment with artificial tears.

PURPOSE: The question of whether artificial tears can lead to objective improvement of ocular surface disease in dry eyes is still unanswered. The aim of the current study is to assess the influence of artificial tears on corneal epithelial permeability of dry eyes. Furthermore, the effect of benzalkonium chloride, used as a preservative of artificial tears, on corneal epithelial permeability is investigated. METHODS: The corneal epithelial permeability of 40 dry eye patients (80 eyes) was measured by computerized objective fluorophotometry before and 6 weeks after treatment with artificial tears containing either polyvinyl pyrrolidone 2% without preservative (20 patients) or polyvinyl pyrrolidone 2% preserved with benzalkonium chloride 0.005% (20 patients). RESULTS: Before treatment, the epithelial permeability of the dry eye patients was found to be 2.7 times that of a control group. After treatment, the epithelial permeability of patients treated with unpreserved polyvinyl pyrrolidone 2% had decreased significantly (-37%; P less than 0.001), whereas patients who had been treated with polyvinyl pyrrolidone 2% preserved with benzalkonium chloride 0.005% showed an increase in epithelial permeability (+21%; P = 0.05%). CONCLUSION: These data suggest that, in dry eyes, treatment with unpreserved artificial tears may lead to an objective improvement in corneal surface disease. However, this effect may be counteracted by preservation of tear substitutes with benzalkonium chloride.

Benzalkonium Compounds↗
PubMed1982

The permeability of large arteries to labeled protein.

Using labeled albumin, the permeability index was determined for the aorta and other arteries of the rabbit after different circulation times. The results were reproducible. Different indices of permeability were obtained for different arteries. When the circulation time of the tracer was extended, the increase in the permeability index was greater for the coronary and femoral arteries than for the aorta. 5-hydroxytryptamine, bradykinin and prostaglandin E2 tended to increase the permeability index. There was no relation to the level of blood pressure. The different indices of permeability obtained for the different arteries were not leveled by the mediators. The permeability index is seen to become greater postmortally.

Animals↗
PubMed1999

Glutamine effects on permeability and ATP content of jejunal mucosa in starved rats.

INTRODUCTION: Starvation induces an increase in intestinal permeability that can be of importance to intestinal integrity. Glutamine is the principal energy source for intestinal enterocytes and is considered essential for gut metabolism, structure and function. The aim of this study was to investigate whether glutamine could improve the ATP content of the mucosa of starved rats and attenuate the permeability perturbation during incubation in vitro in Ussing chamber. METHODS: Segments of jejunum from rats starved for 48 h were mounted in Ussing chambers. Glutamine was added to Krebs-buffer at 0.6mM, 3mM, 6mM and 30mM concentrations on the mucosal side. Cr-EDTA permeation, ATP content of the epithelium mucosa and electrophysiology were studied during 180 min of incubation in Ussing chambers. RESULT: These was a negative linear correlation between ATP content and(51)Cr-EDTA permeability in stripped mucosa. ATP content was reduced in all groups during the experiment. When 30 mM glutamine was added on the mucosal side there was an increase in(51)Cr-EDTA permeability (P< 0.001). There was no effect of glutamine on transepithelial resistance but higher concentrations of glutamine (>3mM) significantly increased the short circuit current. CONCLUSION: Supplementing glutamine to the mucosal side in the Ussing chamber led to an increase in ion pump activity and to an increase in paracellular permeability at the 30mM glutamine concentration. Glutamine did not restore the intracellular ATP level. The increase in permeability was inversely correlated to the mucosal ATP content.

Adenosine Triphosphate↗
PubMed2000

Anion permeability and erythrocyte swelling.

Permeability of cell membranes to cations may increase as a result of membrane oxidation or in certain pathologies. We studied the effects of nonselective increases in cell membrane permeability to univalent cations on the volume of erythrocytes incubated in phosphate-buffered saline (PBS) using amphotericin B (5-10 mg/l suspension) or gramicidin D (10-100 microg/l suspension) as the membrane permeabilizing agents. Both antibiotics caused K+ to leak, Na+ to accumulate intracellularly, and cell volume to increase. The interval needed to reach the equilibrium between the intracellular and extracellular ion concentrations ranged from 30 min to several hours, depending on the antibiotic concentration. In spite of a rapid disappearance of cation transmembrane gradients, cell volume increased relatively slow. Even 24 h after the membrane permeability was changed, the volume of most erythrocytes did not increase to the lytic values (about 1.6 times the normal volume). The slow increase in erythrocyte volume was accounted for by slow changes in the transmembrane Cl- gradient. 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), a specific inhibitor of anion transport, while producing no effect on the transmembrane Na+ and K+ fluxes induced by the antibiotics, significantly inhibited the decrease in the transmembrane Cl- gradient and the increase in erythrocyte volume. Analysis of these data by means of mathematical modeling showed that it failed to satisfactorily describe the experimental kinetics of erythrocyte swelling in response to increases in the membrane permeability to univalent cations if its permeability to Cl was set to be constant. The satisfactory description of this kinetics could be achieved by assuming that the membrane permeability to anions decreased with increasing erythrocyte volume. The results obtained demonstrate that transmembrane anion transport may be considered to be a component of the mechanism responsible for the erythrocyte volume stabilization, because a significant decrease in the swelling rate allows the erythrocytes with damaged membranes to activate a relatively slow (metabolic) mechanisms of cell volume stabilization and/or repair their damaged membranes.

Amphotericin B↗
PubMed2000

Suppression of red cell diffusional water permeability by lipophilic solutes.

The inhibitory effect of a series of neutral lipophilic solutes (methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-amylalcohol, n-hexanol, diethylether, nitrobenzene, and pyridine) on the diffusional water permeability (Pd, tot) of bovine erythrocyte membrane at 25 degrees C was studied in comparison to that of p-chloromercuri benzoate (pCMB). Permeability data were obtained by measuring the transmembrane diffusional water exchange time tau(exch) using an 1H-T2 NMR technique. Maximal inhibition by approximately 50% of Pd, tot was produced by 2 mM pCMB which completely blocked the membrane water channels in 20 min, hence suggesting the channel-to-lipid diffusional water permeability ratio of about 1:1. Furthermore, the maximal inhibitory effect of pCMB in combination with the lipophilic solutes was lower than that of pCMB alone. As pCMB does not interfere with the lipid bilayer, and provided that it blocks the water channels in solute presence as well, this confirms that the solutes induce an increase in the lipid-mediated background water permeability contribution (Pd, lipid) by the formation of aqueous leaks in the membrane hydrophobic barrier. However, faster but less efficient in permeability inhibition than pCMB (either alone or combined with solutes) were the lipophilic solutes alone. Taken together, the results indicate that the lipophilic solutes suppress the membrane total permeability Pd, tot by two opposing effects: a reduction of its channel-mediated part (Pd, channel) to the extent exceeding that of a simultaneous Pd, lipid increase. The inhibitory potency of the solutes tested appears to be correlated with their solubility in the membrane medium.

Alcohols↗
PubMed2001

High resolution imaging of the distribution and permeability of methyl viologen dication in bovine articular cartilage using scanning electrochemical microscopy.

Scanning electrochemical microscopy (SECM) has been used in the induced transfer (SECMIT) mode to image the permeability of a probe cation, methyl viologen (MV(2+)), in samples of articular cartilage. An ultramicroelectrode (UME), scanned just above the surface of a sample, is used to amperometrically detect the probe solute. The resulting depletion of MV(2+) in solution induces the transfer of this cation from the sample into the solution for detection at the UME. The current provides quantitative information on local permeability, provided that the sample-UME distance is known. It is shown that the necessary topographical information can be obtained using the amperometric response for the oxidation of Ru(CN)(4-)(6), which does not permeate into the cartilage matrix. This procedure was validated by marking samples in situ, after electrochemical imaging, with subsequent examination by ex situ interferometry and optical microscopy. Wide variations in the permeability of MV(2+) have been detected by SECMIT. These observations represent the first demonstration of the inhomogeneous permeability of a cation in cartilage on a micrometre scale. The permeability maps show similar features to the proteoglycan distribution, identified by toluidine blue staining, and it is likely that proteoglycans are the main determinant of MV(2+) permeability in articular cartilage.

Animals↗
PubMed2001

Permeability of lipophilic compounds in drug discovery using in-vitro human absorption model, Caco-2.

Highly lipophilic compounds are often encountered in the early stages of drug discovery. The apparent permeability (Papp) of these compounds in Caco-2 cell could be underestimated because of considerable retention by the Caco-2 monolayer and non-specific binding to transwell surface. We have utilized a general approach for the determination of permeability of these compounds, which includes the addition of 1-5% DMSO in the apical (AP) and 4% bovine serum albumin (BSA) in the basolateral (BA) side. Two highly lipophilic and highly protein bound Schering compounds, SCH-A and SCH-B, exhibited poor recovery and low Papp in the conventional Caco-2 system that included 1% DMSO in the AP and BA sides. In contrast, both compounds were well absorbed in cynomolgus monkeys. Inclusion of BSA (up to 4%) in the BA side provided necessary absorptive driving force similar to in vivo sink conditions improving both recovery and Papp of these compounds as well as progesterone, a model highly lipophilic and highly protein bound compound. Whereas, the recovery and Papp of mannitol (high recovery, low permeability) and propranolol (high recovery, high permeability) remained unaffected. The presence of 4% BSA increased Papp of SCH-A, SCH-B, and progesterone by five-, four-, and three-fold, respectively. We also compared this approach with a second, based on the disappearance of the compound from the AP side, which resulted in a reasonable estimate of the permeability (23.3x10(-6) cm/s) for SCH-A. The results demonstrated that the reliable estimates of permeability of highly lipophilic compounds that are subjected to considerable retention by the cell monolayer and exhibit non-specific binding are obtained by the addition of BSA to the BA side.

Caco-2 Cells↗
PubMed2000

The effects of changing middle ear pressure and gas partial pressure on mucosal blood flow and vascular permeability in the chinchilla.

OBJECTIVE: To determine if middle ear (ME) gas composition and/or total pressure regulates local mucosal blood flow (MBF) and vascular permeability. The hypotheses tested are: (1) relatively high local CO2 tensions and/or low O2 tensions increase the ME MBF and vascular permeability; and (2) sub-atmospheric total ME pressure provokes similar effects. METHODS: The responses of ME MBF and vascular permeability parameters were measured during 60 min exposures of chinchilla MEs to one of two test gas mixtures (16.3% O2, 5.1% CO2, balance N2, or 5.3% O2, 15.6% CO2, balance N2) applied at different levels of underpressure (ref. ambient). In the first set of experiments (n = 19), mucosal perfusion parameters were recorded using a Laser Doppler Flowmeter for 60 min before and 60 min after exposure to the experimental conditions. In the second set of experiments (n = 19 chinchillas, 38 ears), the MEs were exposed to the gas mixtures and then maintained for 60 min at ambient pressure or at negative pressures of -200, -400, -600 mmH2O. Fifty minutes into the experiment, the animals were injected intravenously with 60 mg/kg of horseradish peroxidase (HRP). The animals were killed and existing effusion was aspirated, its volume recorded and then analyzed for total protein. From surface preparations of the ME mucosa, vascular leakage sites were measured as percent total surface area using an image analysis program with the threshold window set to discriminate HRP stain. RESULTS: Throughout the 120 min in the first set of experiments, the measured MBF parameters decreased in all exposure groups. Comparisons among groups for the absolute magnitude of the change from baseline showed that high local CO2 partial pressures decreased MBF and ME underpressures increased MBF, but the effects did not achieve statistical significance. The results of the second set of experiments demonstrated no effect of gas composition on any of the measured parameters of vascular permeability. All measures of permeability were linearly related to the magnitude of the underpressure. CONCLUSION: These data support a role for total ME pressure, but not CO2 partial pressure in regulating ME MBF and vascular permeability.

Animals↗