Booke M, Bradford D W, Hinder F, Harper D, Brauchle R W, Traber L D, Traber D L
Department of Anesthesiology, University of Texas Medical Branch, Galveston 77555-0833, USA.
Crit Care Med. 1996 Nov;24(11):1841-8. doi: 10.1097/00003246-199611000-00014.
Inhaled nitric oxide has been shown to be a selective pulmonary vasodilator, leading to reduced pulmonary arterial pressure and improved ventilation/perfusion ratio in the acute respiratory distress syndrome. This local pulmonary vasodilation theoretically can be achieved by the airway application of a short-acting vasodilator, such as prostacyclin. We hypothesized that nebulized prostacyclin has the same properties for selective pulmonary vasodilation as inhaled nitric oxide.
Prospective, experimental study in sheep.
Investigational intensive care unit in a university hospital.
Six adult ewes of the Merino breed.
Sheep (n = 6) were surgically prepared for chronic study. After 5 days of recovery, the sheep had tracheostomies performed under anesthesia. Intubation with a modified Robert-Shaw tube allowed side-separated ventilation. The entire left lung was ventilated with pure nitrogen, whereas the right lung was ventilated with pure oxygen. Nitric oxide and prostacyclin were added in different concentrations to the nitrogen, with which the left lung was ventilated.
The blood flows to the left and right lungs were measured with ultrasonic flow probes on the common and left pulmonary artery. Measurements were taken after each compound had been administered for 10 mins at a predefined dose. Both inhaled nitric oxide and nebulized prostacyclin caused effective, selective, dose-dependent pulmonary vasodilation. Inhaled nitric oxide was able to abolish hypoxic pulmonary vasoconstriction when insufflated into the animals at a concentration of 50 ppm of nitrogen, but 100 ppm of nitric oxide had no further effect. Prostacyclin, at a dosage of 10 micrograms/min, showed maximum pulmonary vasodilation, which could not be further increased by doubling the dosage. However, prostacyclin produced less dilation than high doses of nitric oxide, and its maximum pulmonary vasodilation was comparable with that effect obtained under ventilation with 20 ppm of nitric oxide.
Both drugs selectively dilated the pulmonary vasculature in ventilated alveoli. Prostacyclin nebulization is an excellent tool to reduce pulmonary hypertension and to improve the ventilation/perfusion ratio. Prostacyclin nebulization can be used without the highly sophisticated technical equipment that is needed for controlled nitric oxide inhalation, and may therefore become a new, noninvasive therapeutic approach for treatment of adult respiratory distress syndrome in hospitals that cannot provide nitric oxide inhalation.
吸入一氧化氮已被证明是一种选择性肺血管扩张剂，可降低急性呼吸窘迫综合征患者的肺动脉压并改善通气/血流比值。理论上，这种局部肺血管扩张可通过气道应用短效血管扩张剂（如前列环素）来实现。我们假设雾化吸入的前列环素具有与吸入一氧化氮相同的选择性肺血管扩张特性。
对绵羊进行的前瞻性实验研究。
大学医院的研究重症监护病房。
6只美利奴品种成年母羊。
对绵羊（n = 6）进行手术准备以进行长期研究。恢复5天后，在麻醉下对绵羊进行气管切开术。使用改良的罗伯特-肖氏管插管可实现双侧分隔通气。整个左肺用纯氮通气，而右肺用纯氧通气。将不同浓度的一氧化氮和前列环素添加到用于左肺通气的氮气中。
用超声流量探头在总肺动脉和左肺动脉上测量流向左、右肺的血流量。在以预定义剂量给予每种化合物10分钟后进行测量。吸入一氧化氮和雾化吸入的前列环素均引起有效、选择性、剂量依赖性的肺血管扩张。当以50 ppm的氮气浓度向动物体内吹入吸入一氧化氮时，能够消除低氧性肺血管收缩，但100 ppm的一氧化氮则没有进一步的效果。剂量为10微克/分钟的前列环素显示出最大的肺血管扩张，将剂量加倍也无法进一步增加扩张效果。然而，前列环素产生的扩张作用小于高剂量的一氧化氮，其最大肺血管扩张作用与在20 ppm一氧化氮通气条件下获得的效果相当。
两种药物均能选择性地扩张通气肺泡内的肺血管。雾化吸入前列环素是降低肺动脉高压和改善通气/血流比值的一种极佳方法。雾化吸入前列环素的使用无需用于控制一氧化氮吸入的高度复杂技术设备，因此可能成为无法提供一氧化氮吸入治疗的医院治疗成人呼吸窘迫综合征的一种新的非侵入性治疗方法。
