Department of Anesthesiology, Investigational Intensive Care Unit, The University of Texas Medical Branch, and Shriners Hospitals for Children, Galveston, Texas 77550, USA.
Shock. 2011 Jun;35(6):626-31. doi: 10.1097/SHK.0b013e31820fe671.
Different isoforms of nitric oxide (NO) synthase are critically involved in the development of pulmonary failure secondary to acute lung injury. Here we tested the hypothesis that simultaneous blockade of inducible and neuronal NO synthase effectively prevents the pulmonary lesions in an ovine model of acute respiratory distress syndrome induced by combined burn and smoke inhalation injury. Chronically instrumented sheep were allocated to a sham-injured group (n = 6), an injured and untreated group (n = 6), or an injured group treated with simultaneous infusion of selective inducible and neuronal NO synthase inhibitors (n = 5). The injury was induced by 48 breaths of cotton smoke and a third-degree burn of 40% total body surface area. All sheep were mechanically ventilated and fluid resuscitated. The injury induced severe pulmonary dysfunction as indicated by decreases in PaO2/FiO2 ratio and increases in pulmonary shunt fraction, ventilatory pressures, lung lymph flow, and lung wet/dry weight ratio. The treatment fully prevented the elevations in lymph and plasma nitrate/nitrite levels, pulmonary shunting, ventilatory pressures, lung lymph flow, and wet/dry weight ratio and significantly attenuated the decline in PaO2/FiO2 ratio. In conclusion, simultaneous blockade of inducible and neuronal NO synthase exerts beneficial pulmonary effects in an ovine model of acute respiratory distress syndrome secondary to combined burn and smoke inhalation injury. This novel treatment strategy may represent a useful therapeutic adjunct for patients with these injuries.
不同亚型的一氧化氮合酶（NOS）在急性肺损伤继发的肺衰竭的发展中起着关键作用。在这里，我们检验了这样一个假设，即同时阻断诱导型和神经元型 NOS 可有效预防绵羊急性呼吸窘迫综合征模型中由烧伤和烟雾吸入性损伤引起的肺部病变。对长期接受仪器治疗的绵羊进行分组，分别为假损伤组（n=6）、损伤未治疗组（n=6）和损伤同时给予选择性诱导型和神经元型 NOS 抑制剂治疗组（n=5）。损伤通过 48 次棉烟吸入和 40%全身面积的三度烧伤来诱导。所有绵羊均接受机械通气和液体复苏治疗。损伤引起严重的肺功能障碍，表现为 PaO2/FiO2 比值降低，肺分流分数、通气压力、肺淋巴流量和肺湿/干重比升高。该治疗完全阻止了淋巴和血浆硝酸盐/亚硝酸盐水平、肺分流、通气压力、肺淋巴流量和湿/干重比的升高，并显著减轻了 PaO2/FiO2 比值的下降。总之，同时阻断诱导型和神经元型 NOS 对烧伤和烟雾吸入性损伤引起的绵羊急性呼吸窘迫综合征模型具有有益的肺部作用。这种新的治疗策略可能代表了这些损伤患者的一种有用的治疗辅助手段。
