Aging increases the susceptibility to injurious mechanical ventilation

• Published in: Intensive care medicine 2008-05, Vol.34 (5), p.923-931
• Main Authors: Nin, Nicolás, Lorente, José A., De Paula, Marta, Fernández-Segoviano, Pilar, Peñuelas, Oscar, Sánchez-Ferrer, Alberto, Martínez-Caro, Leticia, Esteban, Andrés
• Format: Article
• Language: English
• Subjects: Age Factors; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthesiology; Animals; Biological and medical sciences; Critical Care Medicine; Disease Susceptibility; Emergency and intensive respiratory care; Emergency Medicine; Experimental; Hypotension - etiology; Intensive; Intensive care medicine; Lung - blood supply; Lung - pathology; Male; Medical sciences; Medicine; Medicine & Public Health; Multiple Organ Failure - etiology; Pain Medicine; Pediatrics; Pneumology/Respiratory System; Positive-Pressure Respiration - adverse effects; Rats; Rats, Wistar; Respiratory Distress Syndrome, Adult - therapy; Risk Factors; Systemic Inflammatory Response Syndrome - etiology
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s00134-007-0960-0

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 (V T  = 9 ml/kg and PEEP = 5 cm H 2 O, control) or with an injurious strategy (V T  = 35 ml/kg and PEEP = 0 cm H 2 O, overventilated; n  = 6 for each group). Measurements and results Mean arterial pressure and airway pressures (P AW ) 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-V T induced hypotension, increase in mean P AW , 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.