title: Pulmonary responses to overventilation in late multiple organ failure.
abstract: BACKGROUND
  Patients with multiple organ failure (MOF) require mechanical ventilation for several days. The enormous significance of the ventilation strategy for the outcome of these patients is well appreciated. However, most studies have focused on the onset and the early phase of MOF. It was the aim of the current study to investigate the effect of ventilation in the course of MOF.
  
  
  METHODS
  Using a model where mice develop MOF 7-14 days after intraperitoneal injection of zymosan, the authors analyzed lung functions, signaling pathways, and mediator release in response to protective ventilation (end-expiratory pressure -3 cm H2O; end-inspiratory pressure -10 cm H2O) and overventilation (-22.5 cm H2O) in isolated lungs ex vivo.
  
  
  RESULTS
  On day 7, pulmonary compliance, pulmonary resistance, and tidal volume were normal, but vascular resistance was elevated compared with untreated animals. During ex vivo ventilation, these lungs showed enhanced nuclear factor-kappaB activation, Akt kinase phosphorylation, and cytokine release, and this was further aggravated by overventilation. After 14 days, zymosan-treated animals were characterized by pulmonary hypertension, reduced tidal volume, elevated pulmonary resistance, and increased mediator production. However, in these lungs, neither nuclear factor-kappaB activation nor cytokine production where enhanced by overventilation.
  
  
  CONCLUSIONS
  The zymosan model is characterized by pulmonary inflammation, diminished lung functions, and chronic hypertension. Mechanical ventilation with high distending pressures further augmented cytokine production in this chronic model of MOF only if it significantly augmented tidal volume. The authors speculate that these findings may be explained on the basis of different degrees of lung stretch.
authors.affiliation: Division of Pulmonary Pharmacology, Research Center Borstel, Borstel, Germany. suhlig@ukaachen.de
authors.forename: Ulrike
authors.initials: U
authors.lastname: Uhlig
authors.forename: Daniel
authors.initials: D
authors.lastname: Drömann
authors.forename: Torsten
authors.initials: T
authors.lastname: Goldmann
authors.forename: Heike
authors.initials: H
authors.lastname: Dombrowsky
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Vollmer
authors.forename: Peter
authors.initials: P
authors.lastname: Zabel
authors.forename: Stefan
authors.initials: S
authors.lastname: Uhlig
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000473:pathology / Q000503:physiopathology*; D009504:Neutrophils / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010477:Perfusion; D012121:Respiration, Artificial / Q000009:adverse effects*; D012129:Respiratory Function Tests; D015398:Signal Transduction / Q000502:physiology; D015919:Ventilators, Negative-Pressure
chemical_list: D016207:Cytokines; D051058:Oncogene Protein v-akt