Lam Chen F, van Heerden Peter V, Ilett Kenneth F, Caterina Paul, Filion Pierre
Department of Pharmacology, University of Western Australia, Crawley, Australia.
Chest. 2003 Mar;123(3):869-74. doi: 10.1378/chest.123.3.869.
To determine the selective vasodilatory effects of two inhaled "NONOate" aerosols in a closed chest pig model of acute pulmonary hypertension (APH).
APH was induced by IV infusion of the prostaglandin H(2)/thromboxane A(2) receptor agonist (U46619). Aerosolized diethylenetriamine nitric oxide (NO) adduct (DETA/NO, n = 4), dipropylenetriamine NO adduct (DPTA/NO, n = 4) [60 micro mol each], or placebo (n = 4) was delivered via the trachea. Hemodynamic parameters and blood samples were measured before and after inhalation therapy.
Compared to control animals, pulmonary vascular resistance and pulmonary arterial pressure were significantly reduced from 10 to 105 min after DETA/NO administration and from 10 to 45 min after DPTA/NO aerosol administration (p < 0.05). Both aerosols had no significant effect on systemic vascular resistance or systemic BP. Serum nitrite significantly increased after the inhalation of both NONOates (p < 0.01). There was a tendency for reduced intrapulmonary shunting, particularly after treatment with DETA/NO.
Both DETA/NO and DPTA/NO administered as aerosols selectively reduced pulmonary hypertension induced by U46619.
在急性肺动脉高压（APH）的闭胸猪模型中，确定两种吸入性“NONOate”气雾剂的选择性血管舒张作用。
通过静脉输注前列腺素H(2)/血栓素A(2)受体激动剂（U46619）诱导APH。经气管给予雾化的二乙三胺一氧化氮（NO）加合物（DETA/NO，n = 4）、二丙三胺NO加合物（DPTA/NO，n = 4）[各60微摩尔]或安慰剂（n = 4）。在吸入治疗前后测量血流动力学参数和采集血样。
与对照动物相比，给予DETA/NO后10至105分钟以及给予DPTA/NO气雾剂后10至45分钟，肺血管阻力和肺动脉压显著降低（p < 0.05）。两种气雾剂对全身血管阻力或全身血压均无显著影响。吸入两种NONOate后血清亚硝酸盐显著增加（p < 0.01）。肺内分流有减少的趋势，尤其是在DETA/NO治疗后。
作为气雾剂给药的DETA/NO和DPTA/NO均选择性降低了由U46619诱导的肺动脉高压。
