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INTRODUCTION Although the beneficial effects of inducible nitric oxide synthase (iNOS) inhibition in acute lung injury secondary to cutaneous burn and smoke inhalation were previously demonstrated, the mechanistic aspects are not completely understood. The objective of the present study is to describe the mechanism(s) underlying these favourable effects. We(More)
The formation of oxidative stress in the lung and activation of neutrophils are major determinants in the development of respiratory failure after acute lung injury and sepsis. However, the time changes of these pathogenic factors have not been sufficiently described. Twenty-four chronically instrumented sheep were subjected to cotton smoke inhalation(More)
OBJECTIVE Patients with acute lung injury after smoke inhalation often develop pneumonia subsequently complicated by sepsis. This often is a fatal complication. The aim of this study was to develop a standardized and reproducible model of hyperdynamic sepsis after smoke inhalation in sheep. DESIGN Prospective, experimental study in sheep. SETTINGS(More)
Thermal injury results in reduced plasma levels of arginine (Arg). With reduced Arg availability, NOS produces superoxide instead of NO. We hypothesized that Arg supplementation after burn and smoke inhalation (B + S) injury would attenuate the acute insult to the lungs and, thus, protect pulmonary function. Seventeen Suffolk ewes (n = 17) were randomly(More)
In a recent study, we have shown a rapid inflammatory cell influx across the glandular epithelium and strong proinflammatory cytokine expression at 4 hours after inhalation injury. Studies have demonstrated a significant role of nuclear factor kappa B in proinflammatory cytokine gene transcription. This study examines the acute airway inflammatory response(More)
INTRODUCTION Endothelial dysfunction is a hallmark of sepsis, associated with lung transvascular fluid flux and pulmonary dysfunction in septic patients. We tested the hypothesis that methicillin-resistant Staphylococcus aureus (MRSA) sepsis following smoke inhalation increases pulmonary transvascular fluid flux via excessive nitric oxide (NO) production.(More)
Methicillin-resistant Staphylococcus aureus (MRSA)-related pneumonia and/or sepsis are a frequent serious menace. The aim of the study was to establish a standardized and reproducible model of MRSA-induced septic pneumonia to evaluate new therapies. Sheep were operatively prepared for chronic study. After 5 days' recovery, tracheostomy was performed under(More)
In this study we examined the role of inducible nitric oxide synthase (iNOS) in acute respiratory distress syndrome (ARDS) in sheep with severe combined burn and smoke inhalation injury. BBS-2, a potent and highly selective iNOS dimerization inhibitor, was used to exclude effects on the endothelial and neuronal NOS isoforms. Seven days after surgical(More)
Evidence suggests that lung structure and function are partly maintained by a balance between the competing arginine-metabolizing enzymes arginase and nitric oxide (NO) synthase. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. It is metabolized by dimethylarginine dimethylaminohydrolase 2 (DDAH-2), which is oxidant-sensitive.(More)
INTRODUCTION Different isoforms of nitric oxide synthases (NOS) and determinants of oxidative/nitrosative stress play important roles in the pathophysiology of pulmonary dysfunction induced by acute lung injury (ALI) and sepsis. However, the time changes of these pathogenic factors are largely undetermined. METHODS Twenty-four chronically instrumented(More)