Aging increases the susceptibility to injurious mechanical ventilation
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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.
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, 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.
Elderly rats showed increased susceptibility to injurious mechanical ventilation-induced pulmonary injury, vascular dysfunction, and systemic inflammation.
KeywordsMechanical ventilation Inflammation Organ dysfunction Acute lung injury Animal model Vascular dysfunction
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