吸入一氧化氮降低烟雾吸入性损伤肺动脉高压的实验研究

烟雾吸入致肺组织细胞损伤后５ｍｉｎ，行肺灌洗机械通气４ｈ，观察２４。酹明，犬随机分为三组。烟雾吸入后，对照组单纯涓氧；治疗组吸氧加０．００４５％ＮＯ，连续监测１２ｈ血循环动力学化；正常组不致伤。     

The effects of inhaled nitric oxide on cardiac pathology and energy metabolism in a canine model of smoke inhalation injury

OBJECTIVE: The effects of inhaled nitric oxide (NO) on cardiac pathology and energy metabolism were studied in a canine model of smoke inhalation injury. MATERIAL AND METHOD: Twenty-one dogs were randomly divided into three groups: four dogs constituted the normal control group (group N), eight dogs subjected to smoke inhalation followed by O(2) inhalation (FiO(2)=0.45) constituted the injury control group (group C), and nine dogs inhaling a mixture of O(2) and 45ppm nitric oxide after smoke exposure served as the treatment group (group T). Myocardial zymograms were continuously measured, and ventricular muscles were examined for histopathology in the end of the experiment. RESULTS: Lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (alpha-HBD), creatine kinase (CK) and glutamic oxalacetic transaminase (GOT) in group T were less than those in group C(P<0.05, or P<0.01). ATP content and energy charge (EC) in group T were higher significantly than those in group C(P<0.01). Light microscopy and electron microscopy indicated that the ventricular pathologic changes in group T were milder than in control group. CONCLUSION: Nitric oxide inhalation relieved myocardial damage and improved energy metabolism.     

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.     

Effect of inhaled nitric oxide on pulmonary vascular hyperpermeability in sheep following smoke inhalation

Smoke inhalation increases mortality and morbidity in burn patients. We have reported that smoke inhalation increases lung lymph flow, an index of pulmonary transvascular fluid flux and decreases reflection coefficient, an index of microvascular permeability to protein. Nitric oxide has been reported to decrease microvascular permeability to protein. We hypothesize that inhaled nitric oxide decreases pulmonary microvascular hyperpermeability following smoke inhalation. Sheep were prepared for study with a chronic lung lymph fistula, Swan-Ganz, left atrial, and femoral arterial catheters. Occluders were placed on pulmonary veins to measure reflection coefficient. All animals were insufflated with 4 × 12 breaths of cotton smoke. Sheep were randomly divided into two groups: NO (injured, treated with nitric oxide (40 ppm) inhalation, n = 6) and control (injured, not treated, n = 6). Nitric oxide inhalation was started 22 h after the insult. Control animals showed an increase in lung lymph flow, and lung water content. These changes were associated with marked increase in pulmonary microvascular resistance, pulmonary artery pressure, and decrease in reflection coefficient. Nitric oxide inhalation ameliorated the above-mentioned pathological changes. The results suggest that nitric oxide inhalation has potential for beneficial effect in the treatment of patients suffering from smoke inhalation.     

吸入一氧化氮对吸入性损伤患者心功能的影响

目的观察吸入一氧化氮(NO)对吸入性损伤患者心功能的疗效,初步探讨其作用机制. 方法选择12例烧伤伴中度以上吸入性损伤的成年患者,随机分为2组.对照组(C组)6例,按常规治疗;治疗组(T组)6例,行常规治疗+吸入体积分数1×10-6 的NO.两组患者均留置各种导管.于治疗前及治疗后6、12、24、48和72 h观察两组患者各项心功能指标和血浆内皮素(ET)及NO含量的变化,对T组患者ET、NO的变化进行相关性分析. 结果 T组心排出量(CO)和心搏出量(SV)在24 h后显著高于治疗前,其变化早于C组 (P﹤0.05～0.01).T组左室每搏功指数(LVSWI)和右室每搏功指数(RVSWI)与C组相比均改善较早,且两组RVSWI比较差异有显著性意义(P<0.05).与C组比较,T组ET水平明显降低(P﹤0.05～0.01),而血浆NO水平明显升高(P<0.01),此两项指标呈负相关(r＝-0.98,P<0.01). 结论吸入体积分数1×10-6的NO可以改善吸入性损伤患者的心功能,其机制可能是NO对肺血管平滑肌张力具有调节作用.     

内源性一氧化氮在非创伤性缺血预处理中对兔肺的保护作用

目的探讨内源性一氧化氮（NO）在非创伤性缺血预处理（N—WIP）中对兔肺缺血／再灌注（I／R）损伤的保护作用及可能机制。方法采用N-WIP及经典缺血预处理（C-IP）的动物模型，比较两种缺血预处理方法中内源性NO对兔肺在缺血／再灌注损伤中的保护效应。将40只大白兔随机平均分为4组：对照组、I／R组、C—IP组和NWIP组。对比观察各组血清及肺组织中NO2^-／NO3^-、丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性以及肺湿／干重比。结果N—WIP组和C-IP组的兔肺再灌注后NO2^-／NO3^-含量均高于I／R组（P〈0．01），甚至高于对照组（P〈0．05）。两种缺血预处理组SOD活性均高于I／R组（P〈0．01），肺湿／干重比和MDA含量均低于I／R组（P〈0．05，P〈0．01）。结论N-WIP与C-IP对移植肺在缺血／再灌注损伤中具有同等强度的保护作用。其机制可能是通过诱发内源性一氧化氮（NO）舒张血管，从而起到保护血管内皮的效应。     

Role of inhaled nitric oxide in ischaemia-reperfusion injury in the perfused rabbit lung

We have tested if inhaled nitric oxide (NO) is beneficial in ischaemia- reperfusion (IR) lung injury using an isolated perfused rabbit lung model. Ischaemia for 60 min was followed by reperfusion and ventilation with nitric oxide 40 ppm (n = 6) or without nitric oxide ventilation (n = 6) for 60 min. In the control group (n = 6), the lungs were perfused continuously for 120 min. Permeability coefficient (Kfc) and vascular resistance (PVR) were measured serially for 60 min after reperfusion. We also determined the left lung W/D ratio and measured nitric oxide metabolites (NOx) and cGMP concentrations in bronchoalveolar lavage (BAL) fluid from the right lung. IR increased Kfc, PVR and W/D followed by decreased cGMP. Ventilation with nitric oxide restored these changes by preventing the decrease in cGMP. Differences in NOx concentrations in BAL fluid between the control and IR groups were not statistically significant. Our results indicate that IR impaired pulmonary vascular function and resulted in microvascular constriction and leakage. Ventilation with nitric oxide from the beginning of the reperfusion period improved pulmonary dysfunction such as vasoconstriction and capillary leak by restoring cGMP concentrations.      

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.     

The influences of NO and Ach on cGMP levels in two patient populations

Pulmonary hypertension following cardiac surgery is an important factor affecting postoperative mortality, and its mechanism has not been thoroughly clarified. Cardiopulmonary bypass (CPB) can destroy pulmonary endothelium and aggravate pulmonary hypertension. This study is designed to investigate the impacts of CPB on vascular endothelium-dependent relaxation, and the relations of CPB to pulmonary hypertension. Forty patients undergoing valve surgery were involved. According to their preoperative pulmonary arterial pressure (PAP), these patients were divided into pulmonary hypertension group (H group) and normal group (N group). The concentrations of cyclic guanosine monophosphate (cGMP) were measured at baseline conditions, after acetylcholine (Ach) injection, and during nitric oxide (NO) inhalation. Samples were taken before sternotomy and after weaning from CPB, 4 and 12 hours post-CPB. At baseline, the level of cGMP in the H group was lower than that of the N group by 33.9% before CPB. After initiating the CPB, although the level of cGMP continuously decreased in both groups until weaning from CPB (the N group decreased 33.3%, and the H group decreased 59%). At that point cGMP was higher in N group than in the H group (p < .01). The level of cGMP of both groups tended to recover 4 hours after CPB, but only the N group returned to baseline 12 hours after CPB. After injection of Ach, the level of cGMP of both groups followed the same change as in the baseline, except with different numeric value. The level of cGMP in N group rose ranging from 160.0-197.3%, while it rose ranging from 87.7-168.1% in H group. The levels of cGMP were higher in N group than those in H group at all times following injection of Ach (61.4, 173.3, 202.7, and 188.0%) (p < .01). After inhalation of NO, the level of cGMP of both groups followed the same change as the baseline. The level of cGMP in N group rose ranging from 194.8-320.5%. Although the levels of cGMP were higher in N group than those in H group (6.9, 25.3, 23.3, and 16.6%), significant differences were achieved at the 4 and 12 hour post-CPB periods (p < .05 or p < .01, respectively). It was concluded that the injury of vascular endothelial function caused by CPB was more critical in pulmonary hypertension patients.     

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。     

Nitrite Reduces Acute Lung Injury and Improves Survival in a Rat Lung Transplantation Model

Ischemia/reperfusion injury (IRI) is the most common cause of early mortality following lung transplantation (LTx). We hypothesized that nitrite, an endogenous source of nitric oxide (NO), may protect lung grafts from IRI. Rat lung grafts were stored in preservation solution at 4°C for 6 hours. Both grafts and recipients were treated with nitrite. Nitrite treatment was associated with significantly higher levels of tissue oxygenation, lower levels of cytokines and neutrophil/macrophage infiltration, lower myeloperoxidase activity, reduced oxidative injury and increased cGMP levels in grafts than in the controls. Treatment with either a nitric oxide scavenger or a soluble guanylyl cyclase (sGC) inhibitor diminished the beneficial effects of nitrite and decreased cGMP concentrations. These results suggest that nitric oxide, generated from nitrite, is the molecule responsible for the effects of nitrite via the nitric oxide/sGC/cGMP pathway. Allopurinol, a xanthine oxidoreductase (XOR) inhibitor, abrogated the protective effects of nitrite, suggesting that XOR is a key enzyme in the conversion of nitrite to nitric oxide. In vitro experiments demonstrated that nitrite prevented apoptosis in pulmonary endothelial cells. Nitrite also exhibits longer survival rate in recipients than control. In conclusion, nitrite inhibits lung IRI following cold preservation and had higher survival rate in LTx model.     

左肺反向循环逆转终末期肺动脉高压

目的 探讨反向肺循环逆转终末期肺动脉高压的机制.方法 选杂种犬30只,随机分成正常对照组(n=10)、肺动脉高压组(n=10)和肺高压反向组(n=10).观察各组的血流动力学参数、动脉血气、外周血一氧化氮(NO)、一氧化氮合酶(eNOS)、内皮素及其肺组织mRNA表达的变化.结果 终末期肺高压模型犬上行左肺反向循环手术后,平均肺动脉压(MPAP)降低[(17.3±3.5)mm Hg,P<0.01],但与正常犬MPAP[(12.6±4.2)mm Hg]相比仍偏高(P<0.05);动脉血氧分压上升到(96.5±6.4)mm Hg(P<0.01),血浆中eNOS升高[(1.53±0.56)μg/ml,P<0.01],NO分泌量增加[(36.25±6.94)μmol/L,P<0.01],ET的含量减少[(21.37±3.82)pg/ml,P<0.01].eNOS-mRNA在术后表达上调,PEET-mRNA在肺高压时表达上调,而在术后表达下调.结论 左肺反向循环具有可行性,可能通过转换血气交换的解剖位置、提高血氧含量、抑制血管收缩因子的产生,增加血管舒张因子的产生降低肺动脉高压.     

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.     

Inhaled nitric oxide does not alter pulmonary or cardiac effects of fat embolism in dogs after cemented arthroplasty

PURPOSE: We examined the effect of inhaled nitric oxide (NO) on the acute pulmonary hypertension and right ventricular (RV) dilation after fat embolism. METHODS: A bilateral cemented arthroplasty (BCA), created fat embolism in 20 dogs. In Part A, 12 dogs were randomized to an NO group (n=6, inhaled NO 40 ppm before BCA and throughout the study) or a control group (n=6). In Part B, a third group of dogs (n=8) were given NO 20-40 ppm 2-3 min after BCA when pulmonary artery pressure (PAP) increased. Transesophageal echocardiography (TEE) and invasive hemodynamic monitoring evaluated the hemodynamic response to BCA. Postmortem, quantitative morphometry was used to estimate the number of fat emboli and diameter of lung vessel occluded by fat. RESULTS: Part A: The increase in PAP in the NO group (16 +/- 1 to 34 +/- 9 mmHg) within three minutes of BCA was not different from that in the control group (14 +/- 4 to 35 +/- 9 mmHg). Within three minutes of BCA, TEE demonstrated RV dilation in all groups (P < 0.05) but there was no difference in the change in RV area in the NO and control groups. When NO was given after BCA, no difference in PAP or RV dilation was noted from that in the control group. There were no differences, at post mortem, between the groups in the diameter of lung vessel occluded by fat CONCLUSION: Whether given before the embolic insult or two to three minutes after the onset of pulmonary hypertension, inhaled NO did not attenuate the acute pulmonary hypertension or RV dilation after cemented arthroplasty.     

吸入伤犬部分液体通气后血生化指标变化与动脉血氧分压的关系

目的　探讨部分液体通气对吸入性损伤的治疗作用。　方法　制作犬吸入性损伤模型 ,将氟碳缓慢注入肺内实施部分液体通气 ,分别于致伤前、致伤后 2h及部分液体通气治疗 6 0、90min时 ,抽血检测超氧化物歧化酶 (SOD)、丙二醛 (MDA)、一氧化氮 (NO)及动脉血氧分压 (PaO2 )的变化。　结果　与致伤前相比 ,致伤后 2h犬MDA、NO值明显升高 ,SOD、PaO2 值明显下降 (P <0 0 5 ) ;实施部分液体通气后 ,SOD、MDA、NO及PaO2 值基本恢复到伤前水平。　结论　部分液体通气可以提高氧分压 ,抗脂质过氧化 ,减少体内NO的生成 ,对吸入性损伤有一定的治疗作用     

Effects of oxygen and nitric oxide inhalation in a porcine model of recurrent microembolism

BACKGROUND: Inhalation of nitric oxide (iNO) has been proposed for the treatment of acute pulmonary embolism. The present study evaluates the effects of oxygen (O2) and nitric oxide inhalation in a porcine model of sustained pulmonary hypertension induced by recurrent pulmonary microembolism. METHODS: Twelve pigs were embolized under general anesthesia with 300-microm microspheres intravenously three times over a period of seven weeks. Five pigs served as untreated controls. Hemodynamic and gas exchange responses to 100% oxygen and 40 ppm NO inhalation, and their combination (O2+iNO) were measured seven days after the last embolization. RESULTS: Recurrent microembolism caused sustained pulmonary hypertension (pulmonary vascular resistance index; PVRI 408 +/- 57 dyn x s x cm(-5) x m(-2)) as compared to the control group (PVRI 143 +/- 20 dyn x s x cm(-5) m(-2); P<0.05). PVRI was significantly reduced by O2, iNO, and O2+iNO inhalation by 29 +/- 3, 28 +/- 4, and 32 +/- 3%, respectively. CONCLUSION: We conclude that both O2 and iNO are selective pulmonary vasodilators in a porcine model of sustained pulmonary hypertension following recurrent pulmonary microembolism and, therefore, may be useful in the treatment not only in the acute phase of pulmonary embolism but also later in the time course of the disease.     

NO-Inhalation bei herzchirurgischen Eingriffen: Relevanz für die Rechtsherzfunktion?

The right ventricle is more jeopardized by a cardiopulmonary bypass than the left one. Impaired right ventricular performance may profit from an afterload reduction. A selective reduction in pulmonary artery pressure (PAP) or pulmonary vascular resistance (PVR) without impairment of the systemic circulation seems to be possible by inhalation of nitric oxide (NO). Therefore in the present study we looked for influences of NO inhalation on PAP, PVR and right heart parameters immediately after weaning from the bypass. The dependence of endothelial function on age, preoperative heart function and extracorporeal circulation is well established. The relevance of such parameters on NO inhalation was also investigated. Methods. After ethical approval and informed consent were obtained, 20 patients with moderately increased PAP were included in the study. Ten patients inhaled NO at a concentration of 30 ppm; the other group served as a control group. Measurement points were 10 min after the end of extracorporeal circulation (baseline), 3, 10, and 20 min after the start, as well as 10 min after the end of NO inhalation. NO was injected near the tube into the tubing system during inspiration; dosage and monitoring of the concentration were achieved by means of a chemiluminometer. Measured parameters consisted of PAP, PVR, right ventricular ejection fraction and volumes, systemic blood pressure and resistance, central venous pressure, pulmonary capillary wedge pressure, and oxygenation parameters (p_aO₂, p_vO₂, p_aCO₂). Results. The decrease in PAP (from 29.7±3.9 to a minimal 25.4±4.3 mm Hg, P<0.05) and in PVR (from 169.4±51.9 to a minimal 116.3± 60.9 dyn·s·cm^?5, P·0.05) did not improve right heart function. A similar significant increase in SVR was observed in the NO group and in the control group. Age, haemodynamic parameters or duration of the ischaemic phase of the cardiopulmonary bypass did not influence the course of PAP or PVR. Changes in PAP (from 30.0±4.0 to a minimal 26.7±3.6 mm Hg, P<0.05) and PVR (from 149.0±41.5 to a minimal 125.2±51.5 dyn·s·cm^?5, in the control group were not statistically different from those in the NO group. Indicators of intoxication like an increase in NO₂ or methaemoglobin concentrations or changes in compliance or resistance were not observed. Conclusions. Patients with moderate pulmonary hypertension did not profit from NO inhalation immediately after weaning from the cardiopulmonary bypass. The decreases in PAP and PVR found in the NO or control group did not improve right-heart function. When the NO and control group were compared, specific effects of NO inhalation on PAP and PVR must be questioned This could perhaps be explained by data from animal experiments, which found high endogenous NO levels in situations with elevated cytokine levels. Cytokines are increased after extracorporeal circulation. Oxygenation was not impaired by inhalation of relatively high concentrations of NO. For all investigations with NO inhalation not preceded by steady-state conditions, a control group is recommended.     

犬烟雾吸入性损伤早期肺洗出液灌注大鼠肺所致损伤的研究

目的　研究犬烟雾吸入性损伤早期肺洗出液的生物学活性。　方法　获取犬急性烟雾吸入性损伤早期肺洗出液及正常犬肺洗出液。将Wistar大鼠随机分为A(2 8只 )、B(2 9只 )、C(37只 )组 ,每组各取 7只不作处理作为正常对照 ,其余大鼠肺部作如下处理 :A组注入等渗盐水 ,B组注入正常犬肺洗出液 ,C组注入致伤犬肺洗出液。处死各组中正常对照大鼠 ,并于灌注后 4、12、2 4h处死灌注大鼠 ,观察各组大鼠处死前的存活情况、处死后双肺大体变化及组织病理学改变。检测肺组织匀浆中 6 酮 前列腺素F1α/血栓素B2 (PGF1α/TXB2 )、肿瘤坏死因子α(TNF α)、髓过氧化物酶 (MPO)含量及肺毛细血管通透性。　结果　A、B组大鼠处死前均存活 ,C组大鼠非处死死亡 9只。犬吸入性损伤早期肺洗出液可引起大鼠肺产生类似于烟雾吸入性损伤样的病理变化。A、B组大鼠灌注后肺组织PGF1α/TXB2 均有升高倾向 ;C组大鼠灌注后PGF1α/TXB2 逐渐降低 (P <0.0 1),A、B组灌注后肺组织TNF α、MPO含量均无明显变化 (P >0.0 5 ),C组灌注后 4h肺组织TNF α、MPO含量显著增加 ,分别为 (1.0 2± 0 .0 4 )ng/ml、(1.0 1± 0.0 9)U/g肺组织湿重 ,随后下降 (P <0.0 5～ 0.0 1)。肺灌注后4hC组大鼠肺组织毛细血管通透性高于A、B组 (P <0.0 1)。结论　犬     

Effects of Inhaled Nitric Oxide on Postoperative Pulmonary Circulation in Patients with Congenital Heart Disease

Abstract: We studied 22 patients with residual pulmonary hypertension or symptoms of postoperative pulmonary hypertensive crisis. They received low-dose inhalation (10 ppin) of nitric oxide (NO). a selective pulmonary vasodilator, after total correction for ccingenital heart anomalies. Fifteen minutes of NO inhalation improved the pulmonary circulation and lessened the imbalance in the ventilation-perfusion ratio in both groups. Thus, NO inhalation is effective in the treatment of pulmonary hypertension and in the prevention of pulmonary hypertensive crises after total correction for congenital heart anomalies. All patients continued to receive NO therapeuti-cally. The duration of such therapeutic NO inhalation was well correlated with postoperative Qp/Qs (p = 0.014) and RpRs (p = 0.029).