American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Mar 2001
Comparative StudyThe relationship between craniofacial morphology and obstructive sleep apnea in whites and in African-Americans.
Previous studies of craniofacial risk factors for obstructive sleep apnea (OSA) have been based predominantly on cephalometry. However, differences in head form (measured by the cranial index [CI]) and facial form (measured by the facial index [FI]) are considered by anthropologists to provide a basis for structural variation in craniofacial anatomy. We assessed the association of head and facial form with the apnea hypopnea index (AHI) in 364 white individuals and 165 African-Americans. ⋯ CI and FI did not differ in OSA versus non-OSA groups of African-Americans. In subjects with OSA, the CI in whites was again greater and the FI smaller than those in African-Americans (p = 0.007 and p = 0.004, for CI and FI.) We conclude that brachycephaly is associated with an increased AHI in whites but not in African-Americans. The CI may useful in phenotyping and identifying population subsets with OSA.
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Am. J. Respir. Crit. Care Med. · Mar 2001
Protective role of heme oxygenases against endotoxin-induced diaphragmatic dysfunction in rats.
Reactive oxygen species are strongly implicated in diaphragmatic dysfunction during sepsis. We investigated whether the heme oxygenase (HO) pathway, which is a powerful protective cellular system, protects the diaphragm against oxidative stress and contractile failure during sepsis. A basal expression of both the inducible and constitutive HO protein isoforms (HO-1 and HO-2, respectively) was found in the diaphragm. ⋯ By contrast, increased levels of HO-1 expression obtained by pretreatment of rats with hemin, a powerful inducer of HO-1, completely prevented LPS-mediated diaphragmatic oxidative stress and contractile failure. This protective effect was reversed by ZnPP-IX. These results show an important protective role for the HO pathway against sepsis-induced diaphragmatic dysfunction, which could be related to its antioxidant properties.
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Am. J. Respir. Crit. Care Med. · Mar 2001
CommentVentilation-induced chemokine and cytokine release is associated with activation of nuclear factor-kappaB and is blocked by steroids.
Recent clinical trials have shown that the survival of patients with acute respiratory distress syndrome (ARDS) is improved by ventilation with reduced volumes. These studies suggested that overinflation of the lungs causes overactivation of the immune system. The present study investigated the hypothesis that ventilation with increased tidal volumes results in early responses similar to those caused by stimulation with one of the major risk factors for ARDS: bacterial lipopolysaccharide (LPS). ⋯ We conclude that OV evokes early inflammatory responses similar to those evoked by LPS (i.e., NF-kappaB translocation and release of proinflammatory mediators). The NF-kappaB translocation elicited by OV appears to be independent of Toll-like receptor 4 and not due to LPS contamination introduced by the ventilator. Our data further suggest that steroids might be considered as a subsidiary treatment during artificial mechanical ventilation.
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Am. J. Respir. Crit. Care Med. · Mar 2001
Comparative StudyLipopolysaccharide-induced diaphragmatic contractile dysfunction and sarcolemmal injury in mice lacking the neuronal nitric oxide synthase.
In this study we evaluated the role of the neuronal nitric oxide synthase (nNOS) in lipopolysaccharide (LPS)-induced diaphragmatic contractile dysfunction and sarcolemmal injury. Wild-type (WT) mice or mice deficient in the nNOS gene (nNOS(-/-)) were injected with either saline (control) or Escherichia coli LPS (LPS groups) and sacrificed 12 h later. The diaphragm was then examined for NOS expression, NOS activity, and in-vitro contractility. ⋯ In addition, muscle NOS activity and iNOS protein level in nNOS(-/-) mice injected with LPS reached about 10% and 60% of that of WT animals, respectively (p < 0.05 compared with WT animals). Protein level of endothelial NOS isoform in the diaphragm was not altered by LPS injection in either WT or nNOS(-/-) animals. We conclude that nNOS plays a protective role in attenuating the negative influence of sepsis on diaphragmatic contractility but is not involved in the pathogenesis of sepsis-induced sarcolemmal injury.
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Am. J. Respir. Crit. Care Med. · Mar 2001
Role of nitric oxide in vascular permeability after combined burns and smoke inhalation injury.
Patients with severe burn and/or smoke inhalation injury suffer both systemic and pulmonary vascular hyperpermeability. We hypothesized that nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) plays a role in the changes in microvascular permeability seen with this injury. To test the hypothesis, we administered mercaptoethylguanidine (MEG), a selective iNOS inhibitor, to conscious sheep subjected to a combined smoke inhalation and third-degree burn injury to 40% of total body surface area. ⋯ Changes in pulmonary microvascular permeability were significantly suppressed by inhibition of iNOS. However, there was no significant difference between the two study groups in the microvascular permeability of burned tissue. These data suggest that NO produced by iNOS plays an important role in the changes in systemic and pulmonary microvascular permeability in combined smoke inhalation/third-degree burn injury, but does not affect the vascular permeability of third-degree-burned tissue in this type of injury.