Aging increases the susceptibility to injurious mechanical ventilation.
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.
Nin
Nicolás
N
Servicio de Cuidados Intensivos and CIBER de Enfermedades Respiratorias CB06/06/0044, Instituto de Salud Carlos III, 28905 Madrid, Spain.
Lorente
José A
JA
De Paula
Marta
M
Fernández-Segoviano
Pilar
P
Peñuelas
Oscar
O
Sánchez-Ferrer
Alberto
A
Martínez-Caro
Leticia
L
Esteban
Andrés
A
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*