Nachar R A, Pastene C M, Herrera E A, Riquelme R A, Sanhueza E M, Troncoso S, Llanos A J
Unidad de Neonatología del Hospital del Salvador, Santiago, Chile.
High Alt Med Biol. 2001 Fall;2(3):377-85. doi: 10.1089/15270290152608552.
Carbon monoxide (CO) is produced by the action of the heme oxygenase (HO) complex through the oxidation of heme. CO, like nitric oxide (NO), is a molecular gas that among other actions stimulates guanylyl cyclase and increases cGMP levels in smooth muscle cells, regulating the vascular tone. Acute hypoxia generates pulmonary hypertension and increases the expression of inducible HO isoform (HO-1) in the vascular endothelium. Inhaled NO causes a potent pulmonary vasodilation. We hypothesized that inhaled CO might produce similar actions as NO on pulmonary vascular resistance (PVR). To test our contention, we studied the effects of inhaled CO (40 ppm) in the augmented PVR observed during hypoxemia. Five chronically instrumented German Merino sheep were submitted to a protocol consisting of 20 min of normoxemia (N), 20 min of isocapnic hypoxemia (H20), 20 min of isocapnic hypoxemia plus CO 40 ppm (H40), and 20 min of recovery (R). In the control protocol, we did not administer inhaled CO. Arterial gases and pH, percentage of carboxyhemoglobin (COHb), systemic and pulmonary arterial pressure, systemic and pulmonary vascular resistance, and cardiac output were measured during each period. During H20 period, there was a significant increase in cardiac output and PVR in sheep submitted to both protocols. The sheep treated with inhaled CO (H40 + CO) showed a modest but significant decrease (16%) in the elevated PVR. Our data indicate that inhaled CO decreases pulmonary vascular resistance associated with acute hypoxemia in adult sheep.
一氧化碳（CO）由血红素加氧酶（HO）复合物作用于血红素氧化产生。CO与一氧化氮（NO）一样，是一种分子气体，它除了具有其他作用外，还能刺激鸟苷酸环化酶并增加平滑肌细胞中的环磷酸鸟苷（cGMP）水平，从而调节血管张力。急性缺氧会导致肺动脉高压，并增加血管内皮中诱导型HO同工型（HO-1）的表达。吸入NO会引起强烈的肺血管舒张。我们推测吸入CO可能对肺血管阻力（PVR）产生与NO相似的作用。为了验证我们的观点，我们研究了在低氧血症期间观察到的PVR升高时吸入CO（40 ppm）的影响。五只长期植入仪器的德国美利奴羊接受了一个实验方案，包括20分钟的常氧血症（N）、20分钟的等碳酸血症性低氧血症（H20）、20分钟的等碳酸血症性低氧血症加40 ppm CO（H40）以及20分钟的恢复（R）。在对照方案中，我们未给予吸入CO。在每个时间段测量动脉血气和pH值、碳氧血红蛋白（COHb）百分比、体循环和肺动脉压、体循环和肺血管阻力以及心输出量。在H20时间段，接受两种方案的绵羊的心输出量和PVR均显著增加。吸入CO治疗的绵羊（H40 + CO）升高的PVR出现适度但显著的降低（16%）。我们的数据表明，吸入CO可降低成年绵羊与急性低氧血症相关的肺血管阻力。
