American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 1998
Comparative StudyEffects of dipyridamole and inhaled nitric oxide in pediatric patients with pulmonary hypertension.
Inhaled nitric oxide (iNO) causes selective pulmonary vasodilation by increasing pulmonary vascular levels of cyclic guanosine monophosphate (cGMP). Dipyridamole, a drug with several putative vasodilator mechanisms, is an inhibitor of cGMP-specific phosphodiesterases (PDE5); it therefore has the potential to increase pulmonary vascular cGMP levels, lower pulmonary vascular resistance, augment iNO-induced pulmonary vasodilation, and attenuate excessive pulmonary vasoreactivity. To test dipyridamole in the pulmonary circulation, we studied pediatric patients undergoing cardiac catheterization who had severe resting pulmonary hypertension (Group 1; n = 11) or exaggerated acute hypoxia-induced pulmonary vasoconstriction (Group 2; n = 4). ⋯ In Group 2, Ppa and the pulmonary-to-systemic resistance ratio (Rp/Rs) increased to suprasystemic levels during acute hypoxia. Pretreatment with dipyridamole blunted the increase in Ppa and Rp/Rs during repeat hypoxia, keeping Ppa at a subsystemic level and Rp/Rs < 1. We conclude that: (1) dipyridamole nonselectively reduces PVRI, primarily through an increase in CI; (2) in combination with iNO, dipyridamole augments the decrease in PVRI in some patients; and (3) dipyridamole blunts the severity of acute hypoxic pulmonary vasoconstriction in children with exaggerated hypoxic pressor responses.
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Am. J. Respir. Crit. Care Med. · Nov 1998
ReviewCellular and molecular mechanisms regulating airway smooth muscle proliferation and cell adhesion molecule expression.
Asthma as well as bronchiolitis obliterans and chronic bronchitis are chronic lung diseases characterized by airflow obstruction and airway inflammation. Although asthma typically induces reversible airflow obstruction, in some patients airflow obstruction becomes irreversible. The irreversible airway remodeling that occurs in asthma has been attributed in part to increased smooth muscle mass. ⋯ In addition, new evidence reveals that direct cell- cell interaction between immunocytes and airway smooth muscle may also modulate airway smooth muscle cell function. Studies have shown that activated T lymphocytes can adhere to cultured airway smooth muscle, and the functional consequence of this adherence is the upregulation of cell adhesion molecules and the stimulation of DNA synthesis in human airway smooth muscle cells. The identification of the critical regulatory sites that mediate airway smooth muscle cell proliferation or modulate cell adhesion molecule expression in these cells may improve our understanding of the mechanisms that regulate airway inflammation and possibly provide new therapeutic approaches to alter airway remodeling seen in patients with chronic airflow obstruction.
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Am. J. Respir. Crit. Care Med. · Nov 1998
Comparative StudyA computed tomography scan assessment of regional lung volume in acute lung injury. The CT Scan ARDS Study Group.
The lobar and cephalocaudal distribution of aerated and nonaerated lung and of PEEP-induced alveolar recruitment is unknown in acute lung injury (ALI). Dimensions of the lungs and volumes of aerated and nonaerated parts of each pulmonary lobe were measured using a computerized tomographic quantitative analysis and compared between 21 patients with ALI and 10 healthy volunteers. Distribution of PEEP-induced alveolar recruitment along the anteroposterior and cephalocaudal axis and influence of the resting volume of nonaerated lower lobes were also assessed. ⋯ In ALI, loss of lung volume involves predominantly lower lobes. The thorax shortens along its cephalocaudal axis. PEEP-induced alveolar recruitment predominates in nondependent and cephalad lung regions and is inversely correlated with the resting volume of nonaerated lung.
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Am. J. Respir. Crit. Care Med. · Nov 1998
Positive end-expiratory pressure improves gas exchange and pulmonary mechanics during partial liquid ventilation.
Partial liquid ventilation (PLV) with perflubron (PFB) has been proposed as an adjunct to the current therapies for the acute respiratory distress syndrome (ARDS). Because PFB has been also referred to as "liquid PEEP," distributing to the most gravity-dependent regions of the lung, less attention has been paid to the amount of applied positive end-expiratory pressure (PEEP). We hypothesized that higher PEEP levels than currently applied are needed to optimize gas exchange, and that the lower inflection point (LIP) of the pressure-volume curve could be used to estimate the amount of PEEP needed when the lung is filled with PFB. ⋯ Pulmonary shunt, and ratio of dead space volume to tidal volume (VD/VT) decreased, and static lung compliance increased with PEEP at LIP +1 cm H2O (p < 0.05). No changes were observed in hemodynamics. We conclude that increasing the dose of PFB shifts the LIP to the left, and that setting PEEP at LIP +1 cm H2O improves gas exchange at moderate to high doses of PFB.
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Am. J. Respir. Crit. Care Med. · Nov 1998
Prostaglandins E2 and F2alpha reduce exhaled nitric oxide in normal and asthmatic subjects irrespective of airway caliber changes.
Cyclooxygenase products modulate the expression of nitric oxide synthase (NOS) in certain cell types. We determined the effect of prostaglandins (PG) E2 and F2alpha on exhaled nitric oxide (NO) concentrations measured by chemiluminescence. Inhaled PGE2 and PGF2alpha significantly reduced exhaled NO. ⋯ Although the prostaglandins did not change FEV1 in normal subjects, PGE2 caused an increase in asthmatics (from 3.6 +/- 0.3 L to 3.8 +/- 0.4 L, p < 0.05) and PGF2alpha caused a transient reduction in FEV1 from 4.0 +/- 0.2 L to 3.5 +/- 0.2 L (p < 0.05). To further determine the relationship between bronchoconstriction and exhaled NO levels, we examined the effect of inhaled methacholine which did not change exhaled NO concentrations in normal and asthmatic subjects despite a greater than 20% fall in FEV1 in asthmatics. Therefore, PGE2 and PGF2alpha reduce exhaled NO, an effect not related to airway caliber changes but which may result from an inhibition of nitric oxide synthase (NOS), particularly inducible NOS (iNOS).