Wessel D L, Adatia I
Cardiac Intensive Care Unit, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Adv Pharmacol. 1995;34:475-504. doi: 10.1016/s1054-3589(08)61104-7.
We have presented our experience with the use of inhaled nitric oxide in children with congenital heart disease and pulmonary hypertension, which indicates that nitric oxide is a selective pulmonary vasodilator that may improve patient management, particularly after surgical procedures requiring cardiopulmonary bypass. Indeed, we have now seen several patients in whom all resuscitative maneuvers for the treatment of pulmonary hypertensive crises were unsuccessful until inhaled nitric oxide was added to the therapeutic regimen. In addition, our studies using inhaled nitric oxide as an investigational probe point toward endothelial injury as a contributor to post-cardiopulmonary bypass pulmonary vasoconstriction. Inhaled nitric oxide relieves pulmonary vasoconstriction associated both with left atrial or pulmonary venous hypertension and following the relief of mitral valve or pulmonary venous obstruction. Absence of a response on the usually reactive pulmonary vascular bed of the neonate should prompt a careful search for anatomic, and possibly surgically remediable, pulmonary vascular obstruction. In the short term nitric oxide is less effective in the older patient with obliterative pulmonary vascular disease. It is possible that recent experimental work with long-term nitric oxide inhalation might be applicable to this group of patients. Nitric oxide may have a unique role in the management of the patient after lung transplantation, as it both reduces right ventricular afterload and improves intrapulmonary shunting. Is nitric oxide the ideal agent for testing pulmonary vascular reactivity? Nitric oxide is simple to deliver by either mask or ventilator and, as a trial of vasoreactivity over 15 min, remains free of side effects that might be encountered during long-term administration, such as methemoglobinemia or nitrogen dioxide toxicity. Indeed, no patient developed significant methemoglobinemia after a trial of nitric oxide and neither was a level of nitrogen dioxide above 1 ppm registered during the administration. Thus, nitric oxide gas fulfills many of the ideal characteristics, as suggested by Rubin,92 required of a drug to test the acute responsiveness of the pulmonary circulation. It has better pulmonary dilating effects than systemic, a short half-life, and minimal adverse effects and it can be both easily and quickly administered. Whether it is able to reliably predict the effect of long-term administration of orally active agents awaits confirmation. Certainly, inhaled nitric oxide is rapidly becoming the standard agent to test pulmonary vascular reactivity during diagnostic cardiac catheterization at our institution.
我们介绍了在患有先天性心脏病和肺动脉高压的儿童中使用吸入一氧化氮的经验，这表明一氧化氮是一种选择性肺血管扩张剂，可能改善患者的治疗管理，尤其是在需要体外循环的外科手术后。事实上，我们现在已经看到，在将吸入一氧化氮添加到治疗方案之前，数名患者针对肺动脉高压危象的所有复苏措施均未成功。此外，我们使用吸入一氧化氮作为研究探针的研究表明，内皮损伤是体外循环后肺血管收缩的一个促成因素。吸入一氧化氮可缓解与左心房或肺静脉高压相关的肺血管收缩，以及二尖瓣或肺静脉梗阻解除后的肺血管收缩。新生儿通常有反应的肺血管床若无反应，应促使仔细寻找解剖学上可能可通过手术纠正的肺血管梗阻。短期内，一氧化氮对患有闭塞性肺血管疾病的老年患者效果较差。近期长期吸入一氧化氮的实验工作可能适用于这组患者。一氧化氮在肺移植术后患者的管理中可能具有独特作用，因为它既能降低右心室后负荷，又能改善肺内分流。一氧化氮是测试肺血管反应性的理想药物吗？一氧化氮通过面罩或呼吸机给药很简单，作为15分钟的血管反应性试验，不会出现长期给药可能遇到的副作用，如高铁血红蛋白血症或二氧化氮毒性。事实上，在一氧化氮试验后，没有患者出现明显的高铁血红蛋白血症，给药期间也没有记录到二氧化氮水平超过1 ppm。因此，一氧化氮气体符合鲁宾提出的92种测试肺循环急性反应性的药物所需的许多理想特性。它的肺扩张作用优于全身作用，半衰期短，不良反应最小，且能轻松快速给药。它是否能够可靠地预测口服活性药物长期给药的效果尚待证实。当然，在我们机构的诊断性心导管检查期间，吸入一氧化氮正迅速成为测试肺血管反应性的标准药物。
