American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2004
Comparative StudyBosentan inhibits transient receptor potential channel expression in pulmonary vascular myocytes.
Bosentan, a dual endothelin receptor blocker, has been used clinically to treat idiopathic pulmonary arterial hypertension (IPAH). However, the mechanism of its antiproliferative effect on pulmonary artery smooth muscle cells (PASMCs) remains unclear. A rise in cytoplasmic Ca2+ stimulates PASMC proliferation and the canonical transient receptor potential (TRPC) channels are an important pathway for Ca2+ entry during PASMC proliferation. ⋯ Furthermore, TRPC6 expression in PASMCs from patients with IPAH was greater than in normal PASMCs, and the antiproliferative effect of bosentan was significantly enhanced in IPAH-PASMCs in comparison with normal PASMCs. These observations demonstrate that the antiproliferative effect of bosentan on PASMCs involves the downregulation of TRPC6 channels via a mechanism possibly independent of endothelin receptor blockade. The greater effect of bosentan on IPAH-PASMCs than on normal PASMCs suggests that increased TRPC6 expression and function may be involved in the overgrowth of PASMCs in patients with IPAH.
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Am. J. Respir. Crit. Care Med. · Nov 2004
Editorial Comment Comparative StudyOptimizing lung aeration in positive end-expiratory pressure.
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Am. J. Respir. Crit. Care Med. · Nov 2004
Comparative StudyInfluence of ambient and ventilator output temperatures on performance of heated-wire humidifiers.
Although heated humidifiers are considered the most efficient humidification devices for mechanical ventilation, endotracheal tube occlusion caused by dry secretions has been reported with heated-wire humidifiers. We tested the hypothesis that inlet chamber temperature, influenced by ambient air and ventilator output temperatures, may affect humidifier performance, as assessed by hygrometry. Hygrometry was measured with three different humidifiers under several conditions, varying ambient air temperatures (high, 28-30 degrees C; and normal, 22-24 degrees C), ventilators with different gas temperatures, and two VE levels. ⋯ Hygrometry could be evaluated from condensation on the wall chamber only when ambient air temperature was normal but not with high air temperature. An increase in inlet chamber temperature induced by high ambient temperature markedly reduces the performance of heated-wire humidifiers, leading to a risk of endotracheal tube occlusion. Such systems should be avoided in these conditions unless automatic compensation algorithms are used.
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Am. J. Respir. Crit. Care Med. · Nov 2004
Comparative StudyTomographic study of the inflection points of the pressure-volume curve in acute lung injury.
The inflection points of the pressure-volume curve have been used for setting mechanical ventilation in patients with acute lung injury. However, the lung status at these points has never been specifically addressed. In 12 patients with early lung injury we traced both limbs of the pressure-volume curve by means of a stepwise change in airway pressure, and a computed tomography (CT) scan slice was obtained for every pressure level. ⋯ Aeration at the inflection points was similar in lung injury from pulmonary or extrapulmonary origin. There were no significant changes in hyperinflated lung tissue. These results support the use of the deflation limb of the pressure-volume curve for positive end-expiratory pressure setting in patients with acute lung injury.
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Am. J. Respir. Crit. Care Med. · Nov 2004
Comparative StudyAcute effects of ozone on mortality from the "air pollution and health: a European approach" project.
In the Air Pollution and Health: A European Approach (APHEA2) project, the effects of ambient ozone concentrations on mortality were investigated. Data were collected on daily ozone concentrations, the daily number of deaths, confounders, and potential effect modifiers from 23 cities/areas for at least 3 years since 1990. Effect estimates were obtained for each city with city-specific models and were combined using second-stage regression models. ⋯ The associations with total mortality were independent of SO2 and particulate matter with aerodynamic diameter less than 10 mum (PM10) but were somewhat confounded by NO2 and CO. Individual city estimates were heterogeneous for total (a higher standardized mortality rate was associated with larger effects) and cardiovascular mortality (larger effects were observed in southern cities). The dose-response curve of ozone effects on total mortality during the summer did not deviate significantly from linearity.