Westphal Martin, Cox Robert A, Traber Lillian D, Morita Naoki, Enkhbaatar Perenlei, Schmalstieg Frank C, Hawkins Hal K, Maybauer Dirk M, Maybauer Marc O, Murakami Kazunori, Burke Ann S, Westphal-Varghese Beena B, Rudloff Helen E, Salsbury John R, Jodoin Jeffrey M, Lee Steve, Traber Daniel L
Investigational Intensive Care Unit, Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
Crit Care Med. 2006 May;34(5):1428-36. doi: 10.1097/01.CCM.0000215828.00289.B9.
To examine the effects of combined burn and smoke inhalation injury on hypoxic pulmonary vasoconstriction, 3-nitrotyrosine formation, and respiratory function in adult sheep.
Prospective, placebo-controlled, randomized, single-blinded trial.
University research laboratory.
Twelve chronically instrumented ewes.
Following a baseline measurement, sheep were randomly allocated to either healthy controls (sham) or the injury group, subjected to a 40%, third-degree body surface area burn and 48 breaths of cotton smoke according to an established protocol (n = 6 each). Hypoxic pulmonary vasoconstriction was assessed as changes in pulmonary arterial blood flow (corrected for changes in cardiac index) in response to left lung hypoxic challenges performed at baseline and at 24 and 48 hrs postinjury.
Combined burn and smoke inhalation was associated with increased expression of inducible nitric oxide (NO) synthase, elevated NO2/NO3 (NOx) plasma levels (12 hrs, sham, 6.2 +/- 0.6; injury, 16 +/- 1.6 micromol.L; p < .01) and increased peroxynitrite formation, as indicated by augmented lung tissue 3-nitrotyrosine content (30 +/- 3 vs. 216 +/- 8 nM; p < .001). These biochemical changes occurred in parallel with pulmonary shunting, progressive decreases in Pao2/Fio2 ratio, and a loss of hypoxic pulmonary vasoconstriction (48 hrs, -90.5% vs. baseline; p < .001). Histopathology revealed pulmonary edema and airway obstruction as the morphologic correlates of the deterioration in gas exchange and the increases in airway pressures.
This study provides evidence for a severe impairment of hypoxic pulmonary vasoconstriction following combined burn and smoke inhalation injury. In addition to airway obstruction, the loss of hypoxic pulmonary vasoconstriction may help to explain why blood gases are within physiologic ranges for a certain time postinjury and then suddenly deteriorate.
研究烧伤合并烟雾吸入伤对成年绵羊缺氧性肺血管收缩、3-硝基酪氨酸形成及呼吸功能的影响。
前瞻性、安慰剂对照、随机、单盲试验。
大学研究实验室。
12只长期植入仪器的母羊。
在进行基线测量后，将绵羊随机分为健康对照组（假手术组）或损伤组，按照既定方案对损伤组进行40%的三度体表面积烧伤并吸入48次棉烟（每组n = 6）。通过在基线以及损伤后24小时和48小时对左肺进行缺氧刺激，评估缺氧性肺血管收缩情况，以肺动脉血流变化（校正心脏指数变化）来衡量。
烧伤合并烟雾吸入与诱导型一氧化氮（NO）合酶表达增加、血浆NO2/NO3（NOx）水平升高（12小时，假手术组，6.2±0.6；损伤组，16±1.6微摩尔/升；p <.01）以及过氧亚硝酸盐形成增加有关，肺组织3-硝基酪氨酸含量增加表明了这一点（30±3对216±8纳摩尔；p <.001）。这些生化变化与肺内分流、Pao2/Fio2比值逐渐降低以及缺氧性肺血管收缩丧失同时发生（48小时，与基线相比为-90.5%；p <.001）。组织病理学显示肺水肿和气道阻塞是气体交换恶化和气道压力增加的形态学相关因素。
本研究为烧伤合并烟雾吸入伤后缺氧性肺血管收缩严重受损提供了证据。除气道阻塞外，缺氧性肺血管收缩丧失可能有助于解释为什么伤后一段时间内血气在生理范围内，随后却突然恶化。
