Effects of Foam Microbubbles on Electrical Resistivity and Capillary Pressure of Partially Saturated Porous Media.

Laboratory measurements of capillary pressure (Pc) and the electrical resistivity index (RI) of reservoir rocks are used to calibrate well logging tools and to determine reservoir fluid distribution. Significant studies on the methods and factors affecting these measurements in rocks containing oil, gas, and water are adequately reported in the literature. However, with the advent of chemical enhanced oil recovery (EOR) methods, surfactants are mixed with injection fluids to generate foam to enhance the gas injection process. Foam is a complex and non-Newtonian fluid whose behavior in porous media is different from conventional reservoir fluids. As a result, the effect of foam on Pc and the reliability of using known rock models such as the Archie equation to fit experimental resistivity data in rocks containing foam are yet to be ascertained. In this study, we investigated the effect of foam on the behavior of both Pc and RI curves in sandstone and carbonate rocks using both porous plate and two-pole resistivity methods at ambient temperature. Our results consistently showed that for a given water saturation (Sw), the RI of a rock increases in the presence of foam than without foam. We found that, below a critical Sw, the resistivity of a rock containing foam continues to rise rapidly. We argue, based on knowledge of foam behavior in porous media, that this critical Sw represents the regime where the foam texture begins to become finer, and it is dependent on the properties of the rock and the foam. Nonetheless, the Archie model fits the experimental data of the rocks but with resulting saturation exponents that are higher than conventional gas-water rock systems. The degree of variation in the saturation exponents between the two fluid systems also depends on the rock and fluid properties. A theory is presented to explain this phenomenon. We also found that foam affects the saturation exponent in a similar way as oil-wet rocks in the sense that they decrease the cross-sectional area of water available in the pores for current flow. Foam appears to have competing and opposite effects caused by the presence of clay, micropores, and conducting minerals, which tend to lower the saturation exponent at low Sw. Finally, the Pc curve is consistently lower in foam than without foam for the same Sw.

Chronic exposure to tumor necrosis factor alpha induces retinal pigment epithelium cell dedifferentiation.

BACKGROUND: The retinal pigment epithelium (RPE) is a monolayer of pigmented cells with important barrier and immuno-suppressive functions in the eye. We have previously shown that acute stimulation of RPE cells by tumor necrosis factor alpha (TNFα) downregulates the expression of OTX2 (Orthodenticle homeobox 2) and dependent RPE genes. We here investigated the long-term effects of TNFα on RPE cell morphology and key functions in vitro. METHODS: Primary porcine RPE cells were exposed to TNFα (at 0.8, 4, or 20 ng/ml per day) for 10 days. RPE cell morphology, phagocytosis, barrier- and immunosuppressive-functions were assessed. RESULTS: Chronic (10 days) exposure of primary RPE cells to TNFα increases RPE cell size and polynucleation, decreases visual cycle gene expression, impedes RPE tight-junction organization and transepithelial resistance, and decreases the immunosuppressive capacities of the RPE. TNFα-induced morphological- and transepithelial-resistance changes were prevented by concomitant Transforming Growth Factor ß inhibition. CONCLUSIONS: Our results indicate that chronic TNFα-exposure is sufficient to alter RPE morphology and impede cardinal features that define the differentiated state of RPE cells with striking similarities to the alterations that are observed with age in neurodegenerative diseases such as age-related macular degeneration.

Black tea protects against hypertension-associated endothelial dysfunction through alleviation of endoplasmic reticulum stress.

Hypertensive patients have been found to be associated with elevated levels of homocysteine, known as hyperhomocysteinemia. Homocysteine (Hcy) can induce endoplasmic reticulum (ER) stress in endothelial cells. This study aims to investigate whether black tea (BT) protects against hypertension-associated endothelial dysfunction through alleviation of ER stress. Rat aortae and cultured rat aortic endothelial cells were treated with Hcy, BT extract, and theaflavin-3,3'-digallate (TF3). Male Sprague Dawley rats were infused with angiotensin II (Ang II) to induce hypertension and orally administrated with BT extract at 15 mg/kg/day for 2 weeks. Hcy impaired endothelium-dependent relaxations of rat aortae and led to ER stress in endothelial cells, which were ameliorated by co-incubation of BT extract and TF3. The blood pressure of Ang II-infused rats and plasma Hcy level were normalized by BT consumption. Impaired endothelium-dependent relaxations in renal arteries, carotid arteries and aortae, and flow-mediated dilatations in third-order mesenteric resistance arteries were improved. Elevations of ER stress markers and ROS level, plus down-regulation of Hcy metabolic enzymes in aortae from Ang II-infused rats were prevented by BT treatment. Our data reveal the novel cardiovascular benefits of BT in ameliorating vascular dysfunctions, providing insight into developing BT into beneficial dietary supplements in hypertensive patients.

Aminaphtone in the treatment of pseudophakic cystoid macular edema: a case report.

PURPOSE: Cystoid macular edema (CME) following cataract surgery has been recognized for over 50 years as an important cause of suboptimal post-operative vision. The incidence of CME varies widely, but is likely in the range of 1-2% using modern cataract extraction techniques. We report the case of resolution of post-operative CME after treatment with aminaphtone 75 mg three time a day for one month. METHODS: A 74-year-old causasian woman presented with reduced vision in the left eye after one month from uneventful cataract phacoemulsification. She underwent a complete ophthalmological examination comprehensive of spectral domain optical coherence tomography (SD-OCT) which showed CME and a central foveal thickness (CFT) of 703 micron. The patient was treated with aminaphtone for one month. RESULTS: CME disappeared, the CFT was within normal limits when aminaphtone was ceased, and best corrected visual acuity was 20/20 at the end of the treatment. CONCLUSION: Aminaphtone is a novel proposal in the treatment of pseudophakic cystoid macular edema.

Pharmacological treatment of primary chronic venous disease: rationale, results and unanswered questions.

AIM: The aim of this article was first to review the complex pathophysiological mechanisms responsible for symptoms and signs of primary chronic venous disease (CVD) that allow the identification of targets for pharmacological treatment. The results of CVD treatment with venoactive drugs (VADs) were emphasised and presented in the form of recommendations. The last section raises key questions to be answered to improve protocols for good clinical trials and to draw up future guidelines on these agents. METHODS: The literature has been reviewed here using PubMed and Embase. RESULTS: Venous hypertension appears to underlie all clinical manifestations of primary CVD. Inflammation is key in wall remodelling, valve failure and subsequent venous hypertension. Changes in the haemodynamics of veins are transmitted to the microcirculation, resulting in capillary alteration leading to oedema, skin changes and eventually venous ulceration. Venous symptoms may be the result of interplays between pro-inflammatory mediators and nerve fibres located in the venous wall. Therefore, venous inflammation constitutes a promising therapeutic target for pharmacological intervention, and some available VADs could attenuate various elements of venous inflammation. Based on recent studies, reviews and guidelines, tentative recommendations for the use of VADs were proposed and strong recommendations were given to two of them (micronised purified flavonoid fraction and oxerutins). CONCLUSION: VADs should be accorded a better role in the management of CVD. However, larger and more definitive clinical trials are needed to improve the existing recommendations.

Biomechanics and vasoreactivity of female intramural coronaries in angiotensin II induced hypertension.

Hypertension causes small vessel remodeling, vasomotor alterations. We investigated diameter, tone and mechanics of intramural small coronaries of female rats that received chronic angiotensin treatment to induce hypertension.Angiotensin II infusion (AII, 100 ng/bwkg/min, sc.) was used to establish hypertension in 10 female rats. Other 10 rats served as controls. Following 4 weeks of treatment, side branches of the left anterior descendant coronary (diameter approximately 200 microm) were isolated, cannulated and pressure-diameter curves were registered between 2-90 mmHg. Changes in vessel diameter were measured in Krebs solution, in the presence of thromboxane A2 receptor agonist (U46619, 10(-6) M), bradykinin (BK, 10(-6) M), and finally at complete relaxation (in Ca2+-free solution). Chronic AII treatment raised the mean arterial pressure (130+/-5 mmHg vs. 96+/-2 mmHg, average +/-SEM) significantly. Wall thickness of the AII group was significantly greater (40.2+/-4.2 microm vs. 31.4+/-2.7 microm at 50 mmHg in Ca2+ -free solution), but cross-section of the vessel wall did not differ. Tangentional wall stress and elastic modulus decreased significantly in hypertensive animals. Constrictions in the presence of U46619 were greater in the AII group (24.4+/- 5.6% vs. 14.5+/-3.3% at 50 mmHg). In hypertension, intramural small coronaries showed inward eutrophic remodeling, as a morphological adaptation following AII treatment enhanced thromboxane A2-induced tone.

Drag reducing polymers improve coronary flow reserve through modulation of capillary resistance.

We have shown that drag-reducing polymers (DRP) reduce microvascular resistance and improve myocardial perfusion during coronary stenosis. We used myocardial contrast echocardiography (MCE) and mathematical modeling to define the DRP microvascular effects. A non-flow-limiting left anterior descending (LAD) stenosis was created in 8 dogs. Intramyocardial blood volume, RBC velocity and flow in the LAD and circumflex (CX) beds were obtained from MCE at baseline, and in hyperemia, stenosis, hyperemia + stenosis, and hyperemia + stenosis + DRP. Microvascular resistances were calculated from a lumped-parameter model. During stenosis + hyperemia, LAD bed microvascular resistance increased (p<0.015), and capillary volume (p<0.002) and red cell velocity (p<0.0004) decreased relative to baseline. With DRP, during stenosis and hyperemia, LAD bed microvascular resistance decreased (p<0.04); there was an increase in capillary volume (p<0.007), RBC velocity (p<0.006), and flow (p<0.05). Decreased model-computed capillary resistance accounted for the reduction in LAD bed resistance after DRP. We conclude that DRP improve flow reserve during coronary stenosis by modulating capillary resistance. Primary modification of the rheological properties of blood to affect capillary resistance is a novel approach for the treatment of acute coronary syndromes.

Arterial elasticity and plasma levels of adiponectin and leptin in type 2 diabetic patients treated with thiazolidinediones.

BACKGROUND: Thiazolidinediones (TZDs) improve peripheral insulin sensitivity, but the effect on arterial stiffness is less clear. The aim of the present study was to assess the differential effect of pioglitazone or rosiglitazone on arterial stiffness and plasma levels of adiponectin and leptin in patients with type 2 diabetes mellitus. METHODS: Thirty-five type 2 diabetic subjects were randomly assigned to receive pioglitazone (30 mg/day; n = 14), rosiglitazone (4 mg/day; n = 11), or placebo (medical nutrition therapy; n = 10) for 12 weeks. Changes in plasma glucose, glycosylated hemoglobin, insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, adiponectin, and leptin were evaluated at baseline and after 12 weeks. In parallel, large arterial compliance (C1) and small arterial compliance (C2) were measured at baseline and at the end of treatment period. RESULTS: At 12 weeks, the rosiglitazone (P = 0.026) and pioglitazone (P = 0.004) groups had a significant increase from baseline in adiponectin that was not seen in the medical nutrition therapy group. No significant changes in plasma leptin and in C1 and C2 elasticity indexes were observed over the entire study period in any of the treatment groups. CONCLUSIONS: In this study of patients with type 2 diabetes, treatment with TZDs was associated with a significant improvement in adiponectin levels, although no significant effects were seen on leptin levels and arterial elasticity.

Intracoronary streptokinase after primary percutaneous coronary intervention.

BACKGROUND: Microvascular perfusion is often impaired after primary percutaneous coronary intervention (PCI). We proposed that in situ thrombosis might contribute to poor myocardial perfusion in this setting. To test this hypothesis, we evaluated the effect of low-dose intracoronary streptokinase administered immediately after primary PCI. METHODS: Forty-one patients undergoing primary PCI were randomly assigned to receive intracoronary streptokinase (250 kU) or no additional therapy. Two days later, cardiac catheterization was repeated, and coronary hemodynamic end points were measured with the use of a guidewire tipped with pressure and temperature sensors. In patients with anterior myocardial infarction, the deceleration time of coronary diastolic flow was measured with transthoracic echocardiography. At 6 months, angiography, echocardiography, and technetium-99m single-photon-emission computed tomography were performed. RESULTS: Two days after PCI, all measures of microvascular function (means +/-SD) were significantly better in the streptokinase group than in the control group, including coronary flow reserve (2.01+/-0.57 vs. 1.39+/-0.31), the index of microvascular resistance (16.29+/-5.06 U vs. 32.49+/-11.04 U), the collateral-flow index (0.08+/-0.05 vs. 0.17+/-0.07), mean coronary wedge pressure (10.81+/-5.46 mm Hg vs. 17.20+/-7.93 mm Hg), systolic coronary wedge pressure (18.24+/-6.07 mm Hg vs. 33.80+/-11.00 mm Hg), and diastolic deceleration time (828+/-258 msec vs. 360+/-292 msec). The administration of intracoronary streptokinase was also associated with a significantly lower corrected Thrombolysis in Myocardial Infarction frame count (the number of cine frames required for dye to travel from the ostium of a coronary artery to a standardized distal coronary landmark) at 2 days. At 6 months, however, there was no evidence of a difference between the two study groups in left ventricular size or function. CONCLUSIONS: In our pilot trial, the administration of low-dose intracoronary streptokinase immediately after primary PCI improved myocardial reperfusion but not long-term left ventricular size or function. These findings require clarification in a larger trial. (ClinicalTrials.gov number, NCT00302419.)

Pulsatile hemodynamic effects of candesartan in patients with chronic heart failure: the CHARM Program.

BACKGROUND: Abnormal large artery function and increased pulsatile load are exacerbated by excess angiotensin-II acting through the AT1 receptor and contribute to the pathogenesis and progression of chronic heart failure (CHF). AIMS: To evaluate effects of the AT1 receptor blocker candesartan (N = 30) or placebo (N = 34) on pulsatile hemodynamics in participants with CHF in the CHARM program. METHODS AND RESULTS: Noninvasive hemodynamics were assessed following 6 and 14 months of treatment and averaged. Using calibrated tonometry and aortic outflow Doppler, characteristic impedance was calculated as the ratio of the change in carotid pressure and aortic flow in early systole. Total arterial compliance was calculated by the diastolic area method. Brachial blood pressure, cardiac output and peripheral resistance did not differ between groups. Lower central pulse pressure in the candesartan group (57+/-20 vs. 67+/-17 mmHg, P = 0.043) was accompanied by lower characteristic impedance (200+/-78 vs. 240+/-74 dyne s/cm5, P = 0.039) and higher total arterial compliance (1.87+/-0.70 vs. 1.47+/-0.48 ml/mmHg, P = 0.008). Similar favorable differences were seen when analyses were stratified for ejection fraction (< or = 0.40 vs. >0.40) and baseline angiotensin converting enzyme inhibitor use. CONCLUSIONS: Candesartan has a favorable effect on large artery function in patients with chronic heart failure.

Inhibition of prostaglandin synthesis does not alter the decrease in pre-capillary resistance in the human calf in response to small cumulative increases in venous congestion.

The decrease in pre-capillary resistance in the human calf during gradual cumulative increases in venous congestion pressure has been proposed to represent vasodilator signalling between the venous and arterial microcirculations. The present study investigated whether prostaglandins are involved in this local flow regulation by measuring calf blood flow and microvascular filtration capacity using strain gauge plethysmography in young male subjects before (baseline) and after taking either ibuprofen, an inhibitor of prostaglandin synthesis (1600 mg over 2 days), or placebo. At baseline, inflation of a thigh cuff to 50 mmHg in steps of 10 mmHg, each held for 5 min, did not decrease arterial inflow, confirming a reduction of pre-capillary resistance. Ibuprofen reduced resting calf blood flow by 35% (P<0.001), but flow at a Pcuff (cuff pressure) of 50 mmHg was 97% of this value, i.e. pre-capillary resistance had decreased to the same extent as before inhibition of prostaglandin synthesis. Ibuprofen also reduced microvascular filtration capacity (2.98+/-1.20 compared with 3.71+/-0.89 ml.min-1.100 ml-1.mmHg-1x10(-3); P<0.05), probably due to a combination of reduced arterial inflow and lower venous pressure (8.5+/-5.2 compared with 12.6+/-2.8 mmHg; P<0.05) that moderated capillary hydrostatic pressure to override direct effects of inhibition of prostaglandin synthesis on permeability. Placebo was without effect on any measurement. It is unlikely therefore that prostaglandin-mediated vasodilator signals, which have been demonstrated between paired veins and arteries, are important in local vasodilation in response to venous congestion.

Investigation of vascular responses in endothelial nitric oxide synthase/cyclooxygenase-1 double-knockout mice: key role for endothelium-derived hyperpolarizing factor in the regulation of blood pressure in vivo.

BACKGROUND: Endothelium-dependent dilatation is mediated by 3 principal vasodilators: nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF). To determine the relative contribution of these factors in endothelium-dependent relaxation, we have generated mice in which the enzymes required for endothelial NO and PGI2 production, endothelial NO synthase (eNOS) and cyclooxygenase-1 (COX-1), respectively, have been disrupted (eNOS-/- and COX-1-/- mice). METHODS AND RESULTS: In female mice, the absence of eNOS and COX-1 had no effect on mean arterial blood pressure (BP), whereas BP was significantly elevated in eNOS-/-/COX-1-/- males compared with wild-type controls. Additionally, endothelium-dependent relaxation remained intact in the resistance vessels of female mice and was associated with vascular smooth muscle hyperpolarization; however, these responses were profoundly suppressed in arteries of male eNOS-/-/COX-1-/- animals. Similarly, the endothelium-dependent vasodilator bradykinin produced dose-dependent hypotension in female eNOS-/-/COX-1-/- animals in vivo but had no effect on BP in male mice. CONCLUSIONS: These studies indicate that EDHF is the predominant endothelium-derived relaxing factor in female mice, whereas NO and PGI2 are the predominant mediators in male mice. Moreover, the gender-specific prevalence of EDHF appears to underlie the protection of female eNOS-/-/COX-1-/- mice against hypertension.

Analysis of myogenic mechanisms in renal autoregulation.

To examine whether local myogenic mechanisms account for autoregulation of renal blood flow, a theoretical analysis was undertaken on a model of the pre-glomerular vascular tree consisting of a main and a short, narrow juxtaglomerular segment. At atmospheric extravascular pressure in vitro data are consistent with a relationship r=r0(1 + k - pk) between radius (r) and transmural pressure (p) at p > 60 mmHg, where k can be estimated from in vitro data and r=r0 at complete autoregulatory vasodilation. After introducing r=r(0)(1 + k - pk), Poiseuille's formula was integrated along the main segment, Deltax long, between arterial pressure P(1) and P(2) at the end of the main segment. At the lowest autoregulatory pressure P(1)=65 mmHg pre-glomerular blood flow is F=5Kr(0)(4)/Deltax. At P(1)=140 mmHg a pressure drop of only 17 mmHg to P2=123 mmHg is sufficient to fulfil the criterion for complete autoregulation: F=5Kr(0)(4)/Deltax. Thus, 80% of the total pre-glomerular vascular resistance is localized to the juxtaglomerular segment. Loop diuretics may abolish juxtaglomerular contractility. Calculated flow/pressure relationships after eliminating juxtaglomerular contractility are similar to those obtained after administering ethacrynic acid. If a constant tension hypothesis (r=60r(0)/p) rather than the transmural pressure hypothesis [r=r(0)(1 + k - pk)] applies, complete autoregulation is maintained to P(2)=89 mmHg, but the effect of loop diuretics is not mimicked. In conclusion, high juxtaglomerular contractility may be attributed to a myogenic mechanism only if extravascular pressure in the juxtaglomerular segment is subatmospheric.

Heparin and the nonanticoagulant N-acetyl heparin attenuate capillary no-reflow after normothermic ischemia of the lung.

BACKGROUND: Ischemia-reperfusion injury of the lung frequently occurs after cardiopulmonary bypass, after pulmonary thromboendarterectomy, and especially after lung transplantation. Heparin is known to be protective in ischemia-reperfusion injury, but the risk for bleeding disorders may restrict its use in a variety of diseased conditions. Therefore, we tested the efficiency of nonanticoagulant N-acetyl (NA) heparin to protect from postischemic reperfusion injury of the lung. METHODS: Pentobarbital-anesthetized, mechanically ventilated Lewis rats were heparinized (100 IU/kg) before insertion of catheters. Additionally, animals received either heparin (200 IU/kg; n = 7), NA heparin (1.1 mg/kg; n = 7), or saline (control, n = 7) before ischemia. After normothermic ischemia for 50 minutes, the left lung was reperfused for 120 minutes, or until the death of the animal. The nonischemic right lung was excluded after 10 minutes of reperfusion. RESULTS: Survival rate at 120 minutes of reperfusion was 7 of 7 and 6 of 7 in the heparin and the NA-heparin group, but 0 in 7 in the control group (p < 0.01). At 30 minutes of reperfusion, PaO2, blood flow through the ascending aorta and mean systemic blood pressure were also significantly higher in the heparin and the NA-heparin group when compared with the control group (p < 0.05). Pulmonary vascular resistance was significantly lower in the heparin and the NA-heparin groups, and histologic examination of the lungs from these groups confirmed reperfusion of nutritive alveolar capillaries by the presence of red blood cells. Lack of red blood cells in the alveolar capillaries of lung specimens from the control group indicated failure of capillary reperfusion. CONCLUSIONS: Heparin and NA heparin exert similar protection against capillary no-reflow after normothermic ischemia of the lung. This implies that the protective effect of heparin is mediated by properties different from its anticoagulant activity. Thus the nonanticoagulant N-acetyl heparin may pose a safe new therapeutic approach in lung ischemia-reperfusion injury without increasing the risk of hemorrhagic complications.

Effect of procyanidolic oligomers on the permeability of the blood-brain barrier.

Blood-brain barrier (BBB) is the site of regulatory mechanisms which control the exchange of substances between the brain and the blood through the wall of 'true' brain capillaries with tight junctions between endothelial cells. In some pathological situations the permeability of the BBB is increased because of a partial proteolytic degradation of some constituents of the capillary basement lamina. In such cases it is important to restore normal permeability. The effect of procyanidolic oligomers (PCO) on the BBB was investigated in vivo with quantitative morphologic procedures. We also investigated the action of this drug on collagen and basement lamina constituents (Matrigel) in vitro. Collagenase injected in lateral brain ventricles was shown to increase BBB permeability. Per os administration of PCO to rats greatly increased the resistance of brain capillaries to bacterial collagenase, as shown by the inhibition of the diffusion of fluorescein-isothiocyanate-marked dextran particles from the blood-stream into the brain tissues. Calf skin collagen pretreated in vitro with PCO became more resistant to the hydrolytic action of collagenase. Similar, even more intense protective effect was seen when basal lamina constituents containing type IV collagen was incubated with PCO before exposure to pronase. These in vitro effects may partly explain the in vivo protective effect of PCO against the alteration of brain capillaries by i.v. injected bacterial collagenase.

[Drugs for veno-lymphatic insufficiency]. / Médicaments de l'insuffisance veinolymphatique.

Treatment of venous and lymphatic insufficiency of the lower limbs is based on 3 components: elastic support, venotonic drugs and radical treatments (surgery or sclerotherapy) of insufficient veins. Venotonic drugs have specific indications limited to functional impairment: heavy feeling in the legs, pain and impatience in the evening. There are different categories of venolymphatic drugs. Flavonoids have various pharmacological actions, most notably an increase in venous tone, reduction of capillary permeability and increase of capillary resistance. Choice of a venotonic drug is funded on knowledge of pharmacodynamics and pharmacokinetics of the molecule, critical evaluation of clinical studies, physician's personal experience and drug cost. Venotonic drugs are useful when venous insufficiency leads to functional manifestations. They are especially the treatment of heavy leg syndromes during warm seasons when elastic support is uncomfortable.

Influence of arteriovenular pairing on PAF-induced capillary filtration.

The purpose of this study was to determine the basic mechanism by which leukocyte-endothelial cell adhesion mediates platelet-activating factor (PAF)-induced increases in capillary fluid filtration rate. A modified Landis technique was used to observe fluid filtration from capillaries in the rat mesentery. Hypothetical mechanisms of increased filtration that were tested included 1) a direct action of leukocytes on endothelial cells during transit through the capillaries; 2) an upstream propagated response (via gap junction communication by adjacent endothelial cells) originating at sites of venular leukocyte adhesion; and 3) venule-to-arteriole communication, where mediators produced at the site of venular leukocyte adhesion reach a nearby paired arteriole that delivers the mediators to branching capillaries. Evidence was obtained in opposition to the first two hypotheses. However, in support of the third hypothesis, a significant correlation was found between the extent of arteriolar pairing to venules and the PAF-induced increase in capillary fluid filtration rate. These findings suggest that venule-to-arteriole communication might modify capillary filtration rate during acute inflammation.

Angiotensin-converting enzyme inhibition restores the diffusing capacity for carbon monoxide in patients with chronic heart failure by improving the molecular diffusion across the alveolar capillary membrane.

Conductance of alveolar capillary membrane (DM) and capillary blood volume (VC) are the subcomponents of the pulmonary diffusing capacity for carbon monoxide (DLCO). In chronic heart failure, stress failure of the membrane provides a mechanism for reduced DM and subsequent impairment of DLCO. Angiotensin-converting enzyme inhibition improves DLCO in patients with chronic heart failure. This study was aimed at investigating which of the two subcomponents of DLCO is affected by angiotensin-converting enzyme inhibitors. Twenty-seven patients with NYHA class II to III chronic heart failure (group 1) and 13 age- and sex-matched normal subjects underwent pulmonary function testing with determination of DM and VC, while receiving placebo and 48 h and 1 and 2 months after starting enalapril treatment (10 mg twice daily). Nine similar patients (group 2) received isosorbide dinitrate (40 mg thrice daily) for a month then enalapril for another month, and underwent pulmonary function testing at 48 h and 1 month after starting treatments. Effects of angiotensin-converting enzyme inhibition in normal controls were not significant in the short- or mid-term. In group 1 patients, the only change observed at 48 h was a reduction in VC (probably due to a decrease in capillary pulmonary pressure). There was a marked increase in DM to a similar extent at 1 and 2 months, resulting in a significant improvement in DLCO despite a decrease in VC. In group 2 patients, nitrates failed to improve DLCO and DM, whereas enalapril was as effective as in group 1. These observations suggest a modulatory effect of angiotensin-converting enzyme inhibition on the membrane function which emerges gradually and persists over time and is probably dissociated from changes in pulmonary capillary pressure and VC. Chronic heart failure disturbs the alveolar capillary interface and increases gas diffusion resistance; angiotensin-converting enzyme inhibition restores the diffusive properties of the membrane and gas transfer, and protects the lung when the heart is failing.

Hydrocortisone reinforces the blood-brain properties in a serum free cell culture system.

The increasing number of newly developed drugs demands for functional in vitro models of the blood-brain barrier to determine their brain uptake. Cultured cerebral capillary endothelial cells are considered to be such a model, however in serum containing media they exhibit low electrical resistances and high permeabilities compared to the in vivo situation. Here we report the establishment of a serum-free cell culture model. Withdrawal of serum already caused a twofold increase of transendothelial resistance (TER), which in presence of serum is about 100-150 Omega x cm2. We tested several supplements and found that hydrocortisone is a potent stimulator for the formation of barrier properties. TERs up to 1000 Omega x cm2 were measured in the presence of physiological relevant hydrocortisone concentrations. In correspondence to the TER increase hydrocortisone decreased cell monolayer permeability for sucrose down to 5x10(-7) cm/s, which is close to the in vivo value of 1.2x10(-7) cm/s and by a factor of five lower compared to cultures without hydrocortisone and in presence of serum.