Nin Nicolás, Lorente José A, De Paula Marta, Fernández-Segoviano Pilar, Peñuelas Oscar, Sánchez-Ferrer Alberto, Martínez-Caro Leticia, Esteban Andrés
Servicio de Cuidados Intensivos and CIBER de Enfermedades Respiratorias CB06/06/0044, Instituto de Salud Carlos III, 28905 Madrid, Spain.
Intensive Care Med. 2008 May;34(5):923-31. doi: 10.1007/s00134-007-0960-0. Epub 2008 Jan 5.
To test the hypothesis that aging increases the susceptibility to organ dysfunction and systemic inflammation induced by injurious mechanical ventilation.
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, over-ventilated; n=6 for each group).
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.
Elderly rats showed increased susceptibility to injurious mechanical ventilation-induced pulmonary injury, vascular dysfunction, and systemic inflammation.
验证衰老会增加因机械通气损伤而导致器官功能障碍和全身炎症的易感性这一假说。
在大学医院的动物研究实验室进行的呼吸机诱导性肺损伤动物模型实验研究。
对年轻(3 - 4个月大)和年老(22 - 24个月大)的麻醉Wistar大鼠采用保护性肺通气策略(潮气量 = 9 ml/kg,呼气末正压 = 5 cm H₂O,对照组)或损伤性通气策略(潮气量 = 35 ml/kg,呼气末正压 = 0 cm H₂O,过度通气;每组n = 6)通气60分钟。
监测平均动脉压和气道压力(气道峰压)。测量动脉血气以及血清谷草转氨酶、谷丙转氨酶、乳酸和白细胞介素 - 6。将胸主动脉的血管环置于器官浴槽中进行等长张力记录。我们研究了在去甲肾上腺素预收缩的血管环中乙酰胆碱(10 nM - 10 μM)诱导的舒张,以及在静息血管中去甲肾上腺素(1 nM - 10 μM)诱导的收缩。通过光学显微镜检查肺组织。年轻大鼠的损伤性通气与低氧血症、乳酸代谢性酸中毒、血清谷草转氨酶升高、低血压、体外去甲肾上腺素和乙酰胆碱诱导的血管反应受损以及透明膜形成有关。高潮气量诱导的低血压、平均气道峰压升高、谷草转氨酶和白细胞介素 - 6升高以及乙酰胆碱诱导反应的受损在老年大鼠中比在年轻大鼠中更为明显。
老年大鼠对机械通气损伤诱导的肺损伤、血管功能障碍和全身炎症的易感性增加。