氯喹、地塞米松对烟雾吸入伤大鼠早期肺水肿形成的抑制作用

目的　探讨氯喹、地塞米松对烟雾吸入伤大鼠早期肺水肿的抑制作用。　方法　将健康Wistar大鼠随机分成正常对照组 ,烟雾吸入后 1、3、6、12、2 4h组 ,地塞米松治疗 6、12h组以及氯喹治疗 6、12h组。对大鼠肺组织含水量、肺血管通透性及肺出血量进行测定。　结果　烟雾吸入伤后大鼠肺组织含量和13 1I-白蛋白渗出量明显增加 ,伤后 6h达峰值 ,并持续到伤后 2 4h(P <0 0 1) ;氯喹、地塞米松治疗 6h组肺含水量和13 1I -白蛋白渗出量均明显低于吸入伤 6h组 (P <0 0 1,P <0 0 5 ) ;烟雾吸入伤后肺出血量明显增加 ,以伤后 1h组最明显 ,伤后 2 4h仍明显高于正常对照组 (P <0 0 1) ,氯喹和地塞米松治疗 6h组肺出血量明显低于吸入伤 6h组 (P <0 0 1,P <0 0 5 ) ;氯喹、地塞米松治疗 12h组对上述各值无明显影响 (P >0 0 5 )。　结论　氯喹和地塞米松均能不同程度地降低吸入伤大鼠肺微血管通透性和肺水含量 ,对烟雾吸入伤早期肺水肿的发生具有一定的防治作用     

肺灌洗及外源性肺表面活性物质治疗烟雾吸入性损伤的实验研究

为探讨肺灌洗与外源性肺表面活性物质（ＰＳ）治疗对严重烟雾吸入伤后内源性ＰＳ功能障碍和急性呼吸衰竭的防治效果,作者将重度烟雾吸入伤后Ｗｉｓｔａｒ大鼠经气管插管注入含ＰＳ的等渗盐水或等量盐水行肺灌洗,机械通气４小时,观察２４小时,检测动脉血气、肺水量、静态肺顺应性（Ｃｓｔ）、支气管肺泡灌洗液（ＢＡＬＦ）蛋白含量、ＢＡＬＦ表面张力特性和２４小时病死率等。结果显示：动物伤后立即出现严重缺氧和一氧化碳中毒。烟雾吸入组发生急性呼吸衰竭、高通透性肺水肿和ＰＳ功能障碍。烟雾吸入加灌洗加ＰＳ加机械通气组Ｃｓｔ和ＢＡＬＦ表面张力特性明显改善,氧合能力显著增强,肺水量和ＢＡＬＦ蛋白含量降低,２４小时病死率明显下降。烟雾吸入加灌洗加机械通气组也有一定疗效。作者认为,早期肺灌洗和外源性ＰＳ治疗能有效恢复烟雾吸入所致内源性ＰＳ功能抑制,改善肺功能,防止高通透性肺水肿和呼吸衰竭,降低早期病死率。     

烟雾吸入伤大鼠肺组织细胞凋亡与增殖的变化

目的　观察大鼠烟雾吸入性损伤后肺组织细胞凋亡、细胞增殖的变化规律 ,探讨肺组织损伤修复过程中细胞凋亡的意义。　方法　制作大鼠烟雾吸入性损伤模型 ,随机分为正常对照组、烟雾致伤组 ,应用TUNEL技术及免疫组化技术 ,观察伤后各时相点肺组织细胞凋亡指数及增殖细胞核抗原指数的变化。　结果　 (1)烟雾吸入伤后细胞凋亡指数在伤后 2h增加并维持在高平台区。 (2 )增殖细胞核抗原指数在伤后 12h开始升高 ,3d时达到高峰 ,以后保持在较高水平。　结论　细胞凋亡不仅参与了烟雾吸入伤的早期肺损害 ,也参与了后期修复中增生组织的修饰改建     

大鼠烟雾吸入伤后肺表面活性物质磷脂组分含量的变化及意义

为探讨烟雾吸入后肺表面活性物质（ＰＳ）磷脂组分含量的变化和可能机理及其与ＰＳ活性抑制和肺功能损害的关系，采用大鼠烟雾吸入伤模型，分别检测了正常对照及致伤２，６，１２和２４小时大鼠静态肺顺应性（Ｃｓｔ）、支气管肺泡灌洗液（ＰＡＬＦ）表面张力活性、ＢＡＬＦ和肺匀浆总磷脂（ＴＰＬ）、磷脂酰胆碱（ＰＣ）、磷脂酰肌醇（ＰＩ）、磷脂酰丝氨酸（Ｐｈｓ）、磷脂酰乙醇（ＰＥ）含量、ＢＡＬＦ和肺匀浆中磷脂酶Ａ２（ＰＬＡ２）活性。结果表明动物伤后Ｃｓｔ显著降低；ＢＡＬＦ最小表面张力（ＳＴｍｉｎ）进行性升高；ＢＡＬＦ中ＴＰＬ增加，但ＰＣ（％ＴＰＬ）明显降低，且与Ｃｓｔ和ＳＴｍｉｎ的变化相关显著；肺组织内ＴＰＬ及ＰＣ均下降，并与其中ＰＬＡ２活性升高明显相关。结论：烟雾吸入伤早期肺内ＰＳ磷脂组分含量明显改变，ＰＣ相对含量减少是引起ＰＳ活性抑制及肺功能障碍的主要原因之一，ＰＬＡ２可能在ＰＳ组分异常和（或）含量减少中起重要作用。     

氟碳溶液部分液体通气对烟雾吸入伤大鼠肺静态顺应性的影响

目的:探讨氟碳溶液部分液体通气对烟雾吸入伤大鼠肺静态顺应性的影响。方法:在大鼠烟雾吸入伤模型上建立部分液体通气和机械通气方法,肺总静态顺应性(C_(2.94))和低容量肺顺应性(C_(0.94))用水检压计法测定,同时计算肺扩张指数(EI)。结果:烟雾吸入伤6小时C_(2.49)、C_(0.49)和EI明显低于正常对照组(P<0.01),机械通气治疗对C_(2.94)、C_(0.49)和EI无明显影响(P>0.05);与吸入伤和机械通气组相比,部分液体通气明显增加C_(2.94)、C_(0.49)和EI(P<0.05,P<0.01)。结论:氟碳溶液部分液体通气能明显改善烟雾吸入伤大鼠的肺静态顺应性。     

测定胎盘型碱性磷酸酶判定烟雾吸入所致肺泡Ⅰ型细胞损害

通过动态观察血浆及支气管肺泡灌洗液（ＢＡＬＦ）中ＰＬＡＰ的变化，探讨烟雾吸入所致肺泡Ⅰ型细胞损害及其与肺损伤发生发展的关系，采用大鼠烟雾吸入伤模型，分别检测了正常对照及致伤２，６，１２和２４小时动物的动脉血气、肺水量、ＢＡＬＦ中总蛋白和白蛋白含量，ＢＡＬＦ和血浆中ＰＬＡＰ含量，并作了病理检查。结果表明：动物伤后出现急性呼吸衰竭和严重肺水肿，ＢＡＬＦ中总蛋白及白蛋白含量明显升高；血浆及ＢＡＬＦ中ＰＬＡＰ水平亦显著增加，且与ＢＡＬＦ中蛋白含量的改变相关显著；病理检查亦见严重肺泡Ⅰ型细胞损害。提示ＰＬＡＰ不仅可作为肺泡Ⅰ型细胞损害的标志，而且与烟雾吸入伤后肺泡—毛细血管膜通透性增加有密切关系。     

烟雾吸入损害对氧耗的初步影响(对正压通气的反应)(英)

身体体表烧伤加上烟雾吸入损害常增加早期心肺下稳定和肺以及全身器官功能不良，以往对烟雾吸入伤影响由氧耗（Vo_2）反映的需氧量尚无研究。为此，作者在动物模型中观察了烟雾吸入对Vo_2的影响以及对正压通气(PPV)的反应。取30头重40~45kg的母     

N—乙酰半胱氨酸对烟雾吸入必肺损伤氧化应激的影响

目的：研究N－乙酰半胱氨酸（NAC）对烟雾吸入性肺损伤氧化应激及抗氧能力的影响。方法：采用烟雾吸入性肺损伤大鼠模型，检测吸入伤后肺泡灌洗液（BALF）中白细胞数（WBC），肺组织髓过氧化物酶（MPO）活性，过氧化氢（H2O2）含量，谷胱甘肽（GSH）含量及总抗氧化能力（TAO）。结果：NAC治疗可显降低吸入伤后BALF中WBC数，降低肺组织MPO活性及H2O2含量，并显提高组织GSH含量及TAO水平。结论：NAC治疗可减轻吸入伤后肺脏氧化应激程度，提高肺脏抗氧化应激能力。     

羊左肺吸入性损伤后血浆铜和铁的变化——血栓素拮抗剂BM13.177(Solutroban)的作用

临床和实验室观察血浆铜水平的升高是慢 性肺损害的指标。本研究企图证实高铜血症是否存在于急性肺损害的早期和是否与其病理变化的严重程度有关以及血栓素拮抗剂的影响。由于铜和铁在代谢功能上密切相关,同时测定两者的水平。选择羊左肺烟雾吸入的急性肺损害模型作为研究对象。 13只动物随机分成两组,左肺吸入烟雾造成左肺吸入性损伤。用药组(N=6),Solutroban用生理盐水稀释成1mg/ml。实验时,将10ml     

绵羊烟雾吸入性损伤的病理生理学

烟雾吸入引起的进行性气管支气管和肺实质水肿是由于肺毛细血管渗透性增加所致。本文复制烟雾吸入性损伤的实验模型,以研究人在烟雾吸入后发生的病理生理学改变过程。牧场母羊35头,先在左心房插入硅橡胶导管,同时电灼横膈边缘和左侧胸腔后侧,以中断进入纵隔尾部淋巴结的淋巴管。于第一次手术后1周,18头羊再经右     

The effects of inhaled nitric oxide on the levels of cGMP plasma and lung tissue in a canine model of smoke inhalation injury

The effects of inhaled nitric oxide (NO) on pulmonary hypertension and their mechanisms were studied in a canine model of smoke inhalation injury. Twenty-one dogs were randomly divided into three groups: four dogs constituted the normal control group, eight dogs subjected to smoke inhalation followed by O(2) inhalation (FiO(2)=0.45) constituted the injury control group, and nine dogs inhaling a mixture of O(2) and 45ppm nitric oxide after smoke exposure served as the treatment group. The levels of cyclic guanosine monophosphate (cGMP) in arterial plasma of the treatment group were higher than that of the control group at 5, 8, and 12h after smoke exposure, while the levels of cGMP in lung tissue were also significantly higher compared with that of the control group (P<0.01). The levels of cGMP of injury control group were decreased significantly compared with normal controls (P<0.05). Pulmonary vasoconstriction following smoke inhalation was significantly attenuated by inhalation of NO (P<0.05), which exerted no apparent effect on the systemic circulation (P>0.05). Inhalation of NO may lower pulmonary hypertension induced by smoke inhalation injury in dogs. The selective effect of NO on pulmonary circulation may be attributed to an increase in level of cGMP in smooth muscle cells of the lung tissue after inhalation of NO.     

吸入一氧化氮对室间隔缺损手术后肺动脉高压的疗效观察

目的　观察吸入一氧化氮(nitricoxide,NO)治疗室间隔缺损 (ventricularseptaldefect,VSD)术后肺动脉高压 (pulmonaryhypertension ,PH)的疗效。 方法　 2 0例VSD术后PH病人分别吸入 2 0×10 -6 、6× 10 -6 NO ,监测吸入前后的血流动力学、氧合指标。结果　吸入 2 0× 10 -6 NO后明显降低肺动脉压、肺循环阻力、肺内分流率、肺泡动脉血氧分压差 ,提高动脉血氧分压、氧供指数 ;以上指标停吸NO后恢复吸入NO前水平 ;再吸入 6× 10 -6 NO后恢复吸入 2 0× 10 -6 NO后水平 ,并维持至停吸NO后。吸入前后体循环压及阻力无变化。结论　吸入NO是治疗VSD手术后PH的一种有效的方法。     

一氧化氮治疗吸入性损伤肺动脉高压量效关系的实验研究

目的探讨吸入不同浓度一氧化氮（ＮＯ）治疗兔烟雾吸入性损伤肺动脉高压的量效关系。方法用右心导管检查术连续测定血流动力学指标,观察吸入体积分数为（１、５、１０、２０、３０、４０、５０、６０）×１０－６的ＮＯ对１５只兔烟雾吸入所致肺动脉高压血流动力学的作用。结果吸入（１、５）×１０－６的ＮＯ对平均肺动脉压（ｍＰＡＰ）、肺毛细血管楔压（ＰＣＷＰ）、肺微血管压（Ｐｍｖ）和肺血管阻力（ＰＶＲ）无明显作用（Ｐ＞００５）;吸入（１０、２０、３０、４０、５０、６０）×１０－６的ＮＯ均有降低ｍＰＡＰ、ＰＣＷＰ、Ｐｍｖ的作用（Ｐ＜００５,Ｐ＜００１）;吸入３０×１０－６的ＮＯ即达到最大扩血管效应（Ｐ＜００５,Ｐ＜００１）,再增加吸入ＮＯ的浓度,ＰＶＲ不再进一步降低（Ｐ＞００５）。结论吸入ＮＯ降低烟雾吸入性损伤早期肺动脉压的体积分数以不超过３０×１０－６为宜。     

Inhaled nitric oxide after mitral valve replacement in patients with chronic pulmonary artery hypertension.

Patients with mitral valve disease can develop pulmonary artery hypertension that persists after mitral valve replacement. In 1987, nitric oxide (NO) was reported to be an important factor accounting for the biologic activity of endothelium-derived relaxing factor. Inhaled NO was subsequently reported to be a selective pulmonary vasodilator in animals and patients. Therefore we investigated the vasodilating effect of inhaled NO in patients with mild pulmonary artery hypertension after mitral valve replacement. Six patients who underwent mitral valve replacement for mitral stenosis presented with a mean pulmonary artery pressure greater than 25 mmHg within 24 h after surgery. During mechanical ventilation at FIO2 0.5, NO (36.8-38.4 ppm) was breathed for 10 min. Hemodynamic data were recorded before NO, after 10 min of NO inhalation, and 30 min after the end of NO inhalation. Statistically significant (P < 0.05) hemodynamic response to inhaled NO included a transient decrease in systolic (-10%), diastolic (-8%), and mean (-10%) pulmonary artery pressures; a decrease in pulmonary vascular resistance (-22%); an increase in mixed venous hemoglobin O2 saturation (+6%); and a decrease in arteriovenous O2 content difference (-7%). During NO inhalation, there was no change in systemic arterial or pulmonary wedge pressures. Methemoglobin levels remained < 1%. Inhalation of this concentration of NO for 10 min causes transient pulmonary artery vasodilation and hemodynamic improvement in patients with mild chronic pulmonary artery hypertension after mitral valve replacement.     

Small-dose inhaled nitric oxide attenuates hemodynamic changes after pulmonary air embolism in dogs.

Inhaled nitric oxide (NO) has been used to treat pulmonary hypertension. Experimental studies have suggested therapeutic effects of NO after pulmonary microembolism. We evaluated the protective effects of NO in dogs during a pulmonary air embolism (PAE). NO (3 ppm) was administered to six anesthetized mongrel dogs (NO group) but not to the seven dogs in the control group. After 20 min, each dog received a venous air injection of 2.5 mL/kg. Hemodynamic evaluation was performed, and blood samples were drawn for blood gas analysis before and after NO inhalation and 5-60 min after the PAE. Both arterial blood pressure and cardiac output were decreased in the control group for >15 min after PAE, whereas NO-treated animals showed only transient hypotension. NO attenuated the pulmonary hypertension after PAE, as demonstrated by small (P < 0.05) increases in pulmonary artery pressure and pulmonary vascular resistance index in NO-treated animals (90% and 135%, respectively) compared with the controls (196% and 282%, respectively). These hemodynamic effects of NO were associated with higher mixed venous O2 tensions and saturations in the NO group compared with the controls. We conclude that small-dose NO (3 ppm) attenuated the hemodynamic changes induced by PAE in dogs. This protective effect of NO on hemodynamics is not accompanied by improvement in pulmonary oxygenation in this setting. IMPLICATIONS: In this study, we evaluated the protective effects of inhaled nitric oxide in a pulmonary air embolism setting. Nitric oxide attenuated the hemodynamic changes induced by pulmonary air embolism without improving pulmonary oxygenation.     

Inhaled nitric oxide and nifedipine have similar effects on lung cGMP levels in rats.

Inhaled nitric oxide (NO) may downregulate the endogenous NO/cyclic guanosine monophosphate (cGMP) pathway, potentially explaining clinical rebound pulmonary hypertension. We determined if inhaled NO decreases pulmonary cGMP levels, if the possible down-regulation is the same as with nifedipine, and if regulation also occurs with the cyclic adenosine monophosphate (cAMP) pathway. Rats were exposed to 3 wk of normoxia, hypoxia (10% O2), or monocrotaline (MCT; single dose = 60 mg/kg) and treated with either nothing (control), inhaled NO (20 ppm), or nifedipine (10 mg x kg(-1) x day(-1). The lungs were then isolated and perfused with physiologic saline. Perfusate cGMP, prostacyclin, and cAMP levels were measured. Perfusate cGMP was not altered by inhaled NO or nifedipine in normoxic or MCT rats. Although hypoxia significantly increased cGMP by 128%, both inhaled NO and nifedipine equally prevented the hypoxic increase. Inhibition of the NO/cGMP pathway with N(G)-nitro-L-arginine methyl ester (L-NAME) decreased cGMP by 72% and 88% in normoxic and hypoxic lungs. Prostacyclin and cAMP levels were not altered by inhaled NO or nifedipine. L-NAME significantly decreased cGMP levels, whereas inhaled NO had no effect on cGMP in normoxic or MCT lungs, suggesting that inhaled NO does not inhibit the NO/cGMP pathway. Inhaled NO decreased cGMP in hypoxic lungs, however, nifedipine had the same effect, which indicates the decrease is not specific to inhaled NO. IMPLICATIONS: High pulmonary pressure after discontinuation of inhaled nitric oxide (NO) may be secondary to a decrease in the natural endogenous NO vasodilator. This rat study suggests that inhaled NO either does not alter endogenous NO or that it has similar effects as nifedipine.     

Selective Pulmonary Vasodilation Induced by Aerosolized Zaprinast

Background: Zaprinast, an inhibitor of guanosine-3',5'-cyclic monophosphate (cGMP)-selective phosphodiesterase, augments smooth muscle relaxation induced by endothelium-dependent vasodilators (including inhaled nitric oxide [NO]). The present study was designed to examine the effects of inhaled nebulized zaprinast, alone, and combined with inhaled NO.

Methods: Eight awake lambs with U46619-induced pulmonary hypertension sequentially breathed two concentrations of NO (5 and 20 ppm), followed by inhalation of aerosols generated from solutions containing four concentrations of zaprinast (10, 20, 30, and 50 mg/ml). The delivered doses of nebulized zaprinast at each concentration (mean +/- SD) were 0.23 +/- 0.06, 0.49 +/- 0.14, 0.71 +/- 0.24, and 1.20 +/- 0.98 mg [center dot] kg sup -1 [center dot] min sup -1, respectively. Each lamb also breathed NO (5 and 20 ppm) and zaprinast (0.23 +/- 0.06 mg [center dot] kg sup -1 [center dot] min sup -1) in combination after a 2-h recovery period.

Results: Inhaled NO selectively dilated the pulmonary vasculature. Inhaled zaprinast selectively dilated the pulmonary circulation and potentiated and prolonged the pulmonary vasodilating effects of inhaled NO. The net transpulmonary release of cGMP was increased by inhalation of NO, zaprinast, or both. The duration of the vasodilation induced by zaprinast inhalation was greater than that induced by NO inhalation.     

Inhaled nitric oxide administration during one-lung ventilation in patients undergoing thoracic surgery

OBJECTIVE: To evaluate the effects of inhaled nitric oxide (iNO) on hemodynamics and oxygenation during one-lung ventilation (OLV) in the lateral decubitus position in patients undergoing elective thoracic surgery. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Thirty consecutive patients scheduled for thoracotomy. INTERVENTIONS: Anesthesia consisted of thoracic epidural analgesia combined with general anesthesia (isoflurane, fentanyl, and vecuronium bromide). Systemic and pulmonary circulations were monitored with a radial artery catheter and a pulmonary artery catheter. Inhaled NO, 40 ppm, was administered during OLV, and the inhaled gas mixture was monitored for NO and nitrogen dioxide (NO2). Hemodynamic and oxygenation data were collected before and during inhaled NO administration. MEASUREMENTS AND MAIN RESULTS: Inhaled NO caused a reduction of pulmonary vascular resistance index from 249 +/- 97.6 dyne. sec. cm(-5) to 199.3 +/- 68.9 dyne. sec. cm(-5) (p < 0.05), without effects on systemic hemodynamics or impairment of oxygenation. A stratification of the patients according to values of QS/QT (< 30%, 30% to 44%, > or = 45%), PaO(2)/fraction of inspired oxygen (> or = 200, 100 to 199, < 100), and pulmonary hypertension (mean pulmonary arterial pressure < 24 or > or = 24 mmHg) showed that inhaled NO causes a significant reduction of mean pulmonary artery pressure in patients with pulmonary hypertension, mainly as a result of a reduction of pulmonary vascular resistance index, and improves oxygenation by reducing intrapulmonary shunt in patients with severe hypoxemia during OLV. CONCLUSIONS: Inhaled NO administration neither significantly decreased mean pulmonary arterial pressure in patients with normal pulmonary artery pressure nor improved oxygenation in nonhypoxic patients. Nevertheless, inhaled NO is effective in patients with pulmonary hypertension and hypoxemia during OLV.     

Intermittent nitric oxide combined with intravenous dipyridamole in a piglet model of acute pulmonary hypertension

Continuous administration of inhaled nitric oxide is now widely used as a potent and selective pulmonary vasodilator. We have evaluated the effects of IV dipyridamole, a cyclic guanosine monophosphate (cGMP) phosphodiesterase inhibitor, on the magnitude and duration of action of inhaled nitric oxide (NO)-mediated pulmonary vasodilation. We hypothesized that inhibition of cGMP degradation could augment and prolong the pulmonary vasodilating effects of NO and allow for intermittent NO inhalation. In eight anesthetized and mechanically ventilated piglets, IV U-46619, a thromboxane A(2) analog, was used to induce pulmonary hypertension. The effects of 2, 5, and 10 ppm of NO, delivered during 4 min for each concentration and followed by a 10-min NO-free interval after each NO concentration, were evaluated without and with dipyridamole. Pulmonary vascular resistance decreased from 825 +/- 49 dynes. s. cm(-5) (U-46619) to 533 +/- 48 dynes. s. cm(-5) (10 ppm NO) (P < 0.05 versus U-46619) and 396 +/- 42 dynes. s. cm(-5) (dipyridamole 10 microg kg-1x min-1 and 10 ppm NO) (P <0.05 versus NO), and cardiac output increased from 1.93 +/- 0.09 L/min to 2.03 +/- 0.13 L/min and 2.60 +/- 0.30 L/min (P < 0.05 versus NO). Mean arterial blood pressure decreased from 90 +/- 5 mm Hg (10 ppm NO) to 75 +/- 3 mm Hg (dipyridamole plus 10 ppm NO) (P < 0.01). The pulmonary vasodilation obtained with NO alone could be prolonged from 12 to 42 min when inhaled NO was combined with IV dipyridamole, accounting for a time-weighted reduction in NO exposure by 72%. We conclude that dipyridamole augments the effects of NO on right ventricular afterload, allows for intermittent NO inhalation, and can significantly reduce exposure to NO. IMPLICATIONS: IV dipyridamole prolongs the action of inhaled nitric oxide (NO) in a piglet model of acute pulmonary hypertension. Intermittent NO inhalation combined with IV dipyridamole decreases pulmonary artery pressure for a prolonged period of time and reduces exposure to NO.     

Effects of intravenous Zaprinast and inhaled nitric oxide on pulmonary hemodynamics and gas exchange in an ovine model of acute respiratory distress syndrome

BACKGROUND: Inhaled nitric oxide (No) selectively dilates the pulmonary vasculature and improves gas exchange in acute respiratory distress syndrome. Because of the very short half-life of NO, inhaled NO is administered continuously. Intravenous Zaprinast (2-o-propoxyphenyl-8-azapurin-6-one), a cyclic guanosine monophosphate phosphodiesterase inhibitor, increases the efficacy and prolongs the duration of action of inhaled NO in models of acute pulmonary hypertension. Its efficacy in lung injury models is uncertain. The authors hypothesized that the use of intravenous Zaprinast would have similar beneficial effects when used in combination with inhaled NO to improve oxygenation and dilate the pulmonary vasculature in a diffuse model of acute lung injury. METHODS: The authors studied two groups of sheep with lung injury produced by saline lavage. In the first group, 0, 5, 10, and 20 ppm of inhaled NO were administered in a random order before and after an intravenous Zaprinast infusion (2 mg/kg bolus followed by 0.1 mg. kg-1. min-1). In the second group, inhaled NO was administered at the same concentrations before and after an intravenous infusion of Zaprinast solvent (0.05 m NaOH). RESULTS: After lavage, inhaled NO decreased pulmonary arterial pressure and resistance with no systemic hemodynamic effects, increased arterial oxygen partial pressure, and decreased venous admixture (all P < 0.05). The intravenous administration of Zaprinast alone decreased pulmonary artery pressure but worsened gas exchange (P < 0.05). Zaprinast infusion abolished the beneficial ability of inhaled NO to improve pulmonary gas exchange and reduce pulmonary artery pressure (P < 0. 05 vs. control). CONCLUSIONS: This study suggests that nonselective vasodilation induced by intravenously administered Zaprinast at the dose used in our study not only worsens gas exchange, but also abolishes the beneficial effects of inhaled NO.