Biomedical subjects

Jean-Francois Pittet

Publications and source records attributed to Jean-Francois Pittet.

4 recordsLinked to original sources

PubMed2003

High tidal volume ventilation induces NOS2 and impairs cAMP- dependent air space fluid clearance.

Tidal volume reduction during mechanical ventilation reduces mortality in patients with acute lung injury and the acute respiratory distress syndrome. To determine the mechanisms underlying the protective effect of low tidal volume ventilation, we studied the time course and reversibility of ventilator-induced changes in permeability and distal air space edema fluid clearance in a rat model of ventilator-induced lung injury. Anesthetized rats were ventilated with a high tidal volume (30 ml/kg) or with a high tidal volume followed by ventilation with a low tidal volume of 6 ml/kg. Endothelial and epithelial protein permeability were significantly increased after high tidal volume ventilation but returned to baseline levels when tidal volume was reduced. The basal distal air space fluid clearance (AFC) rate decreased by 43% (P < 0.05) after 1 h of high tidal volume but returned to the preventilation rate 2 h after tidal volume was reduced. Not all of the effects of high tidal volume ventilation were reversible. The cAMP-dependent AFC rate after 1 h of 30 ml/kg ventilation was significantly reduced and was not restored when tidal volume was reduced. High tidal volume ventilation also increased lung inducible nitric oxide synthase (NOS2) expression and air space total nitrite at 3 h. Inhibition of NOS2 activity preserved cAMP-dependent AFC. Because air space edema fluid inactivates surfactant and reduces ventilated lung volume, the reduction of cAMP-dependent AFC by reactive nitrogen species may be an important mechanism of clinical ventilator-associated lung injury.

Acute Disease↗

PubMed2003

The development of acute lung injury is associated with worse neurologic outcome in patients with severe traumatic brain injury.

OBJECTIVE: The purpose of this study was to determine the incidence of acute lung injury (ALI) in trauma patients with severe traumatic brain injury (TBI), to evaluate the impact of ALI on mortality and neurologic outcome after severe traumatic brain injury (TBI), and to identify whether the development of ALI correlates with the severity of TBI. METHODS: Clinical data were collected prospectively over a 4-year period in a Level I trauma center. Patients included in the study met the following criteria: mechanical ventilation > 24 hours, head Abbreviated Injury Scale score >or= 3, no other body region Abbreviated Injury Scale score >or= 3, and age between 18 and 54 years. ALI was defined using international consensus criteria. Glasgow Outcome Scale scores were assessed at 3 and 12 months. Bivariate comparisons were made between ALI and non-ALI groups. Multivariate analysis with stepwise logistical regression was used to assess independent factors on mortality. The patient's admission head computed tomographic (CT) scan was graded using the Marshall system, and the presence and size of specific intracranial abnormality was noted. Glasgow Coma Scale (GCS) score, Marshall CT scan score, and intracranial abnormality were correlated with the development of ALI. RESULTS: One hundred thirty-seven patients with isolated head trauma were enrolled in the study over a 4-year period. Thirty-one percent of patients with severe TBI developed ALI. Head trauma patients with ALI had a significantly higher ISS, a greater number of days on the ventilator, and a worse neurologic outcome for those who survived their hospitalization. Mortality was 38% in the ALI group and 15% in the non-ALI group (p = 0.004). Only 3 of 16 (19%) of the deaths within the ALI group were directly related to ALI. By multivariate analysis, only the presence of ALI, older age, and lower initial GCS score were associated with higher mortality. There was no association between ISS, the presence of arterial hypotension (arterial systolic pressure < 90 mm Hg) at admission to the hospital, or the amount of blood transfused and mortality. No correlation was found between the severity of head injury (GCS score, Marshall score, or intracranial abnormality) and development of ALI. CONCLUSION: The development of ALI is a critical independent factor affecting mortality in patients suffering traumatic brain injury and is associated with a worse long-term neurologic outcome in survivors. The risk of developing ALI is not associated with specific anatomic lesions diagnosed by cranial CT scanning.

Abbreviated Injury Scale↗

PubMed2002

Chronic bronchial allergic inflammation increases alveolar liquid clearance by TNF-alpha -dependent mechanism.

Bronchial inflammation in allergic asthma is associated with active exudation from the bronchial tree into the interstitial space of both mucosa and submucosa. The aim of this study was to evaluate epithelial and endothelial permeability as well as alveolar fluid movement in a model of chronic allergic inflammation in Brown-Norway rats sensitized and challenged with ovalbumin (OA). Control groups were challenged with saline solution (C), and rats were immunized by OA but not challenged (Se). Lung sections showed a marked inflammatory infiltrate associated with perivascular and peribronchiolar edema in OA. To measure alveolar liquid clearance, a 5% bovine albumin solution with 1 microCi of (125)I-labeled human albumin was instilled into the air spaces. Alveolar-capillary barrier permeability was evaluated by intravascular injection of 1 microCi of (131)I-labeled albumin. Endothelial permeability was significantly increased in OA, from 0.08 +/- 0.01 in the C group to 0.19 +/- 0.03 in OA group (P < 0.05). Final-to-initial protein ratio was also statistically higher in OA (1.6 +/- 0.05) compared with C (1.38 +/- 0.03, P = 0.01) and Se groups (1.42 +/- 0.03, P = 0.04). Administration of anti-tumor necrosis factor-alpha antibodies within the instillate significantly decreased this ratio (1.32 +/- 0.08, P = 0.003 vs. OA). To conclude, we demonstrated a tumor necrosis factor-alpha-dependent increase in alveolar fluid movement in a model of severe bronchial allergic inflammation associated with endothelial and epithelial leakage.

Albumins↗

PubMed2002

Lidocaine induces a reversible decrease in alveolar epithelial fluid clearance in rats.

BACKGROUND: Lidocaine is widely used in patients with acute cardiac disorders and has also been recently implicated as a possible cause of pulmonary edema after liposuction. The objective of this study was to assess the effect of lidocaine on alveolar fluid clearance, the primary mechanism responsible for the resolution of alveolar edema. METHODS: Alveolar fluid clearance was measured in 29 ventilated rats using our well-validated method over 1 h using a 5% albumin solution instilled into the distal air spaces of the lung. Lidocaine was added to the instilled albumin solution (10(-5) M) or administered intravenously at a dose estimated to achieve a clinically relevant plasma concentration of 10(-5) M. Standard agonists and antagonists were used to determine the effect of lidocaine on alveolar fluid clearance. To determine whether lidocaine acted predominantly on the apical or basal surface, we also used QX314, lidocaine n-ethyl bromide quaternary salt, an analog of lidocaine, which is unable to cross the alveolar epithelium. The effect of lidocaine on the apical epithelial sodium channel transfected in Xenopus oocytes was also studied. RESULTS: Alveolar or intravenous lidocaine decreased alveolar fluid clearance by 50%, an effect that was reversible with the beta2 agonist, terbutaline. Lidocaine acted predominantly on the basal surface of the epithelium because n-ethyl bromide quaternary salt decreased alveolar fluid clearance only when it was given intravenously and because lidocaine did not inhibit the apical epithelial sodium channel when expressed in oocytes. CONCLUSIONS: Lidocaine decreased alveolar fluid clearance by 50%, an effect that may have major clinical implications in the care of patients with cardiac disease or during the perioperative period in some patients. Importantly, the effect of lidocaine was completely reversible with beta2-adrenergic therapy.

Amiloride↗