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. Design and setting: 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 H 2O, overventilated; n = 6 for each group). Measurements and 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 μM) in norepinehrine-precontracted rings, and contractions induced by norepinephrine (1 nM-10 μM) 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. © 2008 Springer-Verlag.