Metabolic dependence of photoreceptors on the choroid in the normal and detached retina.
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PURPOSE: This article assesses the hypothesis that the high blood flow rate and low O(2) extraction associated with the choroidal circulation are metabolically necessary and explores the implications of the spatial relationship between the choroid and the photoreceptors for metabolism in the normal and detached retina. METHODS: The O(2) distribution across the retinal layers was previously measured with O(2)-sensitive microelectrodes in cat. Profiles were fitted to a diffusion model to obtain parameters characterizing photoreceptor O(2) demand. This was a study of simulations based on those parameters. RESULTS: Photoreceptor inner segments have a high O(2) demand (QO(2)), and they are far (20 to 30 microm) from the choroid. These unusual conditions require a large O(2) flux to the inner segments, which in turn requires high choroidal oxygen tension (PO(2)), high choroidal venous saturation (ScvO(2)), low choroidal O(2) oxygen extraction per unit volume of blood, and a choroidal blood flow (ChBF) of at least 500 ml/100 g-min. Movement of the inner segments further from the choroid, which occurs in a retinal detachment, severely reduces the ability of the inner segments to obtain O(2), even for detachment heights as small as 100 microm. Depending on detachment height and assumptions about choroidal and inner retinal PO(2) during elevation of inspired O(2) (hyperoxia), hyperoxia is predicted to partially or fully restore photoreceptor QO(2) during a detachment. CONCLUSIONS: The choroid is not overperfused, but requires a high flow rate to satisfy the normal metabolic demand of the retina. Because the oxygenation of the photoreceptors is barely adequate under normal conditions, detachment has serious metabolic consequences. Hyperoxia is predicted to have clinical benefit during detachment. (+info)
Subset-specific regulation of the lymphatic exit of recirculating lymphocytes in vivo.
(50/863)
The blood-to-lymph recirculation of lymphocytes is required for the maintenance of immune surveillance and the dissemination of memory. Although the ability of lymph-borne cells to recirculate has been well documented, relatively less is known about the migration capacity of PBLs. We have found a clear preference for PBLs to recirculate through s.c. rather than intestinal lymph nodes. This preference could be directly attributed to the migratory characteristics of gammadelta-T cells. gammadelta-T cells were found to express significantly higher levels of L-selectin than other subsets, suggesting that at least some of this preferential migration could be attributed to their interaction with ligands on vascular endothelium. More detailed experiments showed that gammadelta-T cells migrated through lymph nodes with greater efficiency than alphabeta T cells or B cells, which clearly indicated an enhanced ability of gammadelta-T cells to exit lymph nodes in the efferent lymph independent of entry from the blood. This hypothesis was supported by histological examination, where gammadelta-T cells were found almost exclusively in the interfollicular traffic areas within lymph nodes. These data indicate that gammadelta-T cells are the most active recirculating lymphocyte subset in ruminants and suggest new mechanisms to regulate the traffic of lymphocyte subsets through normal lymph nodes. (+info)
Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease.
(51/863)
OBJECTIVES: The purpose of this study was to determine whether lowering homocysteine levels with folic acid, with or without antioxidants, will improve endothelial dysfunction in patients with coronary artery disease (CAD). BACKGROUND: Elevated plasma homocysteine levels are a risk factor for atherosclerosis. Homocysteine may promote atherogenesis through endothelial dysfunction and oxidative stress. METHODS: In a double-blind, placebo-controlled, randomized trial, we used vascular ultrasound to assess the effect of folic acid alone or with antioxidants on brachial artery endothelium-dependent flow-mediated dilation (FMD). Seventy-five patients with CAD (screening homocysteine level > or =9 micromol/liter) were randomized equally to one of three groups: placebo, folic acid alone or folic acid plus antioxidant vitamins C and E. Patients were treated for four months. Plasma folate, homocysteine, FMD and nitroglycerin-mediated dilation were measured before and after four months of treatment. RESULTS: Plasma folate, homocysteine and FMD were unchanged in the placebo group. Compared with placebo, folic acid alone increased plasma folate by 475% (p < 0.001), reduced plasma homocysteine by 11% (p = 0.23) and significantly improved FMD from 3.2 +/- 3.6% to 5.2 +/- 3.9% (p = 0.04). The improvement in FMD correlated with the reduction in homocysteine (r = 0.5, p = 0.01). Folic acid plus antioxidants increased plasma folate by 438% (p < 0.001), reduced plasma homocysteine by 9% (p = 0.56) and insignificantly improved FMD from 2.6 +/- 2.4% to 4.0 +/- 3.7% (p = 0.45), as compared with placebo. Nitroglycerin-mediated dilation did not change significantly in any group. CONCLUSIONS: Folic acid supplementation significantly improved endothelial dysfunction in patients with coronary atherosclerosis. Further clinical trials are required to determine whether folic acid supplementation may reduce cardiovascular events. (+info)
Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure.
(52/863)
OBJECTIVES: To determine the acute effects of type 5 phosphodiesterase inhibition with sildenafil on flow-mediated vasodilation in the brachial artery of patients with chronic heart failure. BACKGROUND: Impaired endothelium-dependent, flow-mediated vasodilation in patients with heart failure is partly attributable to hyporesponsiveness of cyclic guanosine monophosphate (cGMP) mediated vasorelaxation effector mechanisms in vascular smooth muscle. The effect of inhibition of cGMP degradation with sildenafil, a specific type 5 cGMP phosphodiesterase inhibitor, on flow-mediated dilation in heart failure is unknown. METHODS: Flow-mediated vasodilation after release of 1, 3 and 5 min of transient arterial occlusion was measured in the brachial artery with high resolution two-dimensional ultrasound imaging in 48 patients with chronic heart failure before and 1 h after randomized, double-blind assignment to a single oral dose of sildenafil 12.5, 25 or 50 mg or matching placebo. RESULTS: In response to oral administration of a single dose of study drug, the change in flow-mediated vasodilation after release of 1, 3 and 5 min of arterial occlusion was significantly greater in patients receiving sildenafil 25 mg (3.3 +/- 1.9, 3.8 +/- 1.8 and 4.0 +/- 1.8%, respectively, p < 0.05) and patients receiving sildenafil 50 mg (3.7 +/- 1.3, 4.1 +/- 1.1, 3.9 +/- 1.3%, respectively, p < 0.05) than that of patients receiving placebo (0.7 +/- 1.1, 0.2 +/- 1.2, 0.6 +/- 0.8%, respectively). CONCLUSIONS: Acute type 5 phosphodiesterase inhibition with sildenafil 25 and 50 mg increases endothelium-dependent, flow-mediated vasodilation in patients with chronic heart failure when compared with placebo. (+info)
Structure and mechanical properties of resistance arteries in hypertension: role of adhesion molecules and extracellular matrix determinants.
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Abnormalities of resistance arteries may play a role in the pathogenesis and pathophysiology of hypertension in experimental animals and humans. Vessels that, when relaxed, measure <400 microm in lumen diameter act as the major site of vascular resistance and include a network of small arteries (lumen approximately 100 to 400 microm) and arterioles (<100 microm). Because increased peripheral resistance is generated by a narrowed lumen diameter, significant effort has been focused on determining the mechanisms that reduce lumen size. Three important vascular components are clearly involved, including alterations of vascular structure, mechanics (stiffness), and function. Structural abnormalities comprise a reduced lumen diameter and thickening of the vascular media, resulting in an increased media-lumen ratio. Changes in the mechanical properties of an artery, particularly increased stiffness, may also result in a reduced lumen diameter. These vascular abnormalities may be caused or influenced by the expression and/or topographic localization of extracellular matrix components, such as collagen and elastin, and by changes in cell-extracellular fibrillar attachment sites, such as adhesion molecules like integrins. This article discusses the abnormalities of resistance arteries in hypertension and reviews the evidence suggesting an important role for adhesive and extracellular matrix determinants. (+info)
Continuous positive airway pressure and pulmonary and circulatory function after cardiac surgery in infants less than three months of age.
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Continuous positive airway pressure (CPAP) was used to support the ventilation of infants less than 3 months of age who had undergone thoractomy for cardiovascular surgery. The functional residual capacity, which was approximately 30 per cent of predicted at zero CPAP, increased 35 per cent in cyanotic and 33 per cent in acyanotic infants with the application of 5 mm Hg pressure. Increasing airway pressure from zero to 5 mm Hg increased PaO2 4 per cent in cyanotic and 13 per cent in acyanotic infants. There was no change in heart rate, respiratory rate, mean arterial pressure, pH or PaC02 under similar circumstances, but central venous pressure increased 1.5 mm Hg in cyanotic and 0.8 mm Hg in acyanotic infants. (+info)
Changes in venous return parameters associated with univentricular Fontan circulations.
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To clarify the physiology of venous return (Q(vr)) in Fontan circulations, venous return conductance (G(vr)) and mean circulatory filling pressure (P(mcf)) were determined in pentobarbital sodium-anesthetized pigs. Relationships between Q(vr) and right (biventricular, n = 8) or left (Fontan, n = 8) filling pressures are described by straight lines with significant correlation coefficients. Estimated P(mcf) values were correlated with observed P(mcf) values in either circulations (P +info)
Hypersensitivity of circulating progenitor cells to megakaryocyte growth and development factor (PEG-rHu MGDF) in essential thrombocythemia.
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Hematopoietic progenitor cells in 2 myeloproliferative disorders, juvenile chronic myelomonocytic leukemia and polycythemia vera, are known to be hypersensitive to cytokines that control normal progenitor cell proliferation, differentiation, and survival in their respective granulocyte/macrophage and erythroid lineages. Because thrombopoietin controls these functions in the normal megakaryocytic lineage, we asked the question: Are megakaryocytic progenitor cells in the myeloproliferative disorder essential thrombocythemia (ET) hypersensitive to thrombopoietin? Peripheral blood mononuclear cells from patients with ET, or secondary (reactive) thrombocytosis (2 degrees T), or healthy volunteers were grown in strictly serum-free agarose culture containing interleukin 3 (IL-3) and all-trans-retinoic acid, with various concentrations of PEG-rHu megakaryocyte growth and development factor (MGDF). The concentration of cytokine at half-maximum colony number served as a measure of progenitor cell sensitivity. Hypersensitivity to PEG-rHu MGDF was found in circulating progenitors from 18 of 20 (90%) informative patients with presumptive diagnosis ET, 1 of 8 (12.5%) 2 degrees T patients, and none of the 22 healthy volunteers. Median MGDF sensitivity ratio in ET patients was approximately 53 times greater than in the controls. This hypersensitivity, which was also directed to rHu thrombopoietin, was highly specific with respect to cytokine, disease, and cell lineage. We propose that, despite their single pluripotential cell origin, the different clinicopathologic phenotypes in different chronic myeloproliferative disorders are determined by lineage-restricted hypersensitivities of hematopoietic progenitor cells to endogenous cytokines. This work emphasizes the importance of stringent serum-free conditions for revealing true sensitivities to cytokines. The findings also offer a basis for evolving a positive test for ET, a diagnosis now made essentially by exclusion. (+info)