title: Aging increases the susceptibility to injurious mechanical ventilation.
abstract: OBJECTIVE
  To test the hypothesis that aging increases the susceptibility to organ dysfunction and systemic inflammation induced by injurious mechanical ventilation.
  
  
  METHODS
  Experimental study in an animal model of ventilator-induced lung injury in the animal research laboratory in a university hospital.
  
  
  METHODS
  Young (3-4 months old) and old (22-24 months old) anesthetized Wistar rats were ventilated for 60 min with a protective lung strategy (VT=9 ml/kg and PEEP=5 cm H2O, control) or with an injurious strategy (VT=35 ml/kg and PEEP=0 cm H2O, over-ventilated; n=6 for each group).
  
  
  RESULTS
  Mean arterial pressure and airway pressures (PAW) were monitored. Arterial blood gases and serum AST, ALT, lactate, and IL-6 were measured. Vascular rings from the thoracic aorta were mounted in organ baths for isometric tension recording. We studied relaxations induced by acetylcholine (10 nM-10 microM) in norepinephrine-precontracted rings, and contractions induced by norepinephrine (1 nM-10 microM) in resting vessels. Lungs were examined by light microscopy. Injurious ventilation in young rats was associated with hypoxemia, lactic metabolic acidosis, increased serum AST, hypotension, impairment in norepinephrine and acetylcholine-induced vascular responses ex vivo and hyaline membrane formation. The high-VT induced hypotension, increase in mean PAW, AST, and IL-6, and the impairment in acetylcholine-induced responses were significantly more marked in aged than in young rats.
  
  
  CONCLUSIONS
  Elderly rats showed increased susceptibility to injurious mechanical ventilation-induced pulmonary injury, vascular dysfunction, and systemic inflammation.
authors.affiliation: Servicio de Cuidados Intensivos and CIBER de Enfermedades Respiratorias CB06/06/0044, Instituto de Salud Carlos III, 28905 Madrid, Spain.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Nin
authors.forename: José A
authors.initials: JA
authors.lastname: Lorente
authors.forename: Marta
authors.initials: M
authors.lastname: De Paula
authors.forename: Pilar
authors.initials: P
authors.lastname: Fernández-Segoviano
authors.forename: Oscar
authors.initials: O
authors.lastname: Peñuelas
authors.forename: Alberto
authors.initials: A
authors.lastname: Sánchez-Ferrer
authors.forename: Leticia
authors.initials: L
authors.lastname: Martínez-Caro
authors.forename: Andrés
authors.initials: A
authors.lastname: Esteban
mesh_terms: D000367:Age Factors; D000818:Animals; D004198:Disease Susceptibility; D007022:Hypotension / Q000209:etiology; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology*; D011175:Positive-Pressure Respiration / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D012307:Risk Factors; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology*