Effects of inhaled nitric oxide on pulmonary hemodynamics and gas exchange in an ovine model of ARDS.
Effects of inhaled nitric oxide on pulmonary hemodynamics and gas exchange in an ovine model of ARDS.
复制标题
吸入一氧化氮对 ARDS 绵羊模型肺血流动力学和气体交换的影响。
DOI：
10.1152/jappl.1994.76.1.345
复制
发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Zapol,WM
中科院分区：
文献类型：
--
作者：
Rovira,I;Chen,TY;Winkler,M;Kawai,N;Bloch,KD;Zapol,WM
吸入低浓度的一氧化氮（NO）气体会导致通气肺区域的选择性肺血管舒张。NO激活可溶性鸟苷酸环化酶，增加鸟苷3′，5 ′-环一磷酸（cGMP）。抑制NO合成增强缺氧性肺血管收缩。因此，我们研究了吸入NO和输注NO合成抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）对麻醉和机械通气的双侧灌洗诱导急性肺损伤绵羊肺血管压力-流量关系、气体交换和血浆cGMP水平的独立和联合作用。灌洗后，吸入60 ppm的NO可降低肺动脉压（PAP）和阻力，而无任何全身血流动力学效应，增加动脉PO 2，减少静脉混合物（Qva/QT;所有P < 0.05），而不改变心输出量（QT）、混合静脉PO 2或O2摄取，这是肺内分流的主要决定因素。吸入NO时，PAP-左房压差（PAP-QT）和Qva/QT降低（均P < 0.05），且与QT无关，其变化是机械性的。L-NAME输注引起全身和肺血管收缩，并在整个QT范围内增加PAP-QT梯度，而Qva/QT没有改变。吸入NO后L-NAME输注产生肺血管舒张和降低Qva/QT的程度与单独吸入NO相同。吸入60 ppmNO后5 ~ 10 min，输注L-NAME前后动脉血浆cGMP水平升高80%（均P < 0.05）。在L-NAME后无呼吸时，我们测量了一致的经肺cGMP动静脉梯度[5和10分钟分别为31 +/- 8和33 +/- 7（SE）pmol/ml;均P < 0.05]。在该急性肺损伤模型中，在L-NAME给药之前或之后吸入NO降低了Qva/QT，最可能是通过增加通气肺区域中的cGMP浓度并引起选择性肺血管舒张。
Inhaling low concentrations of nitric oxide (NO) gas causes selective pulmonary vasodilation of ventilated lung regions. NO activates soluble guanylate cyclase, increasing guanosine 3′,5′-cyclic monophosphate (cGMP). Inhibition of NO synthesis enhances hypoxic pulmonary vasoconstriction. Therefore we examined independent and combined effects of NO inhalation and infusion of NG-nitro-L-arginine methyl ester (L-NAME), an NO synthesis inhibitor, on pulmonary vascular pressure-flow relationships, gas exchange, and plasma cGMP levels in anesthetized and mechanically ventilated sheep with acute lung injury induced by bilateral lavage. After lavage, inhaling 60 ppm by volume of NO decreased pulmonary arterial pressure (PAP) and resistance without any systemic hemodynamic effects, increased arterial PO2, and decreased venous admixture (Qva/QT; all P < 0.05) without altering cardiac output (QT), mixed venous PO2, or O2 uptake, major determinants of intrapulmonary shunt. During NO inhalation, PAP-left atrial pressure gradient (PAP-LAP) and Qva/QT were reduced (both P < 0.05) independently of QT, which was varied mechanically. L-NAME infusion produced systemic and pulmonary vasoconstriction and increased PAP-LAP gradient across the entire range of QT, whereas Qva/QT, was not changed. NO inhalation after L-NAME infusion produced pulmonary vasodilation and decreased Qva/QT to the same degree as NO inhalation alone. Five to 10 min after inhalation of 60 ppm NO, before and after L-NAME infusion, arterial plasma cGMP levels were increased by 80% (both P < 0.05). With NO breathing after L-NAME, we measured a consistent transpulmonary cGMP arteriovenous gradient [31 +/- 8 and 33 +/- 7 (SE) pmol/ml at 5 and 10 min, respectively; both P < 0.05]. NO inhalation before or after L-NAME administration in this acute lung injury model reduced Qva/QT, most likely by increasing cGMP concentration in ventilated lung regions and causing selective pulmonary vasodilation.