Effect of inhaled hydrogen sulfide on metabolic responses in anesthetized, paralyzed, and mechanically ventilated piglets.

OBJECTIVE: Induced hypometabolism may improve the balance between oxygen delivery and consumption and may help sustain tissue viability in critically ill patients with low cardiac output state. Inhaled hydrogen sulfide (H2S) has been shown to induce a suspended animation-like state in mice with a 90% decrease in oxygen consumption. We conducted a preclinical study to explore the potential effect of H2S on metabolic rate in large mammals. DESIGN: Prospective study. SETTING: Animal laboratory in a university hospital. SUBJECTS: Eleven anesthetized, paralyzed, and mechanical ventilated piglets (5.8 +/- 0.7 kg). INTERVENTIONS: The right carotid artery and superior vena cava were cannulated for arterial pressure monitoring and blood gas sampling. Seven piglets were sequentially exposed to 20, 40, 60, and 80 ppm of H2S over a period of 6 hrs (each level for 1.5 hrs) (H2S group), and additionally four piglets were exposed to air over the same period (control group). MEASUREMENTS AND MAIN RESULTS: Ambient temperature was fixed at 22 degrees C throughout. Central body temperature, arterial pressure, and heart rate were continuously monitored. Oxygen consumption and carbon dioxide production were continuously measured using respiratory mass spectrometry. Cardiac output was calculated using the Fick principle. Central temperature and oxygen consumption significantly and linearly decreased over the H2S exposures (p < .0001 for both), the rates of which were significantly less compared with those in the control group (p < .01 for both). Mean arterial pressure increased significantly (p = .007), whereas heart rate (p = .14), cardiac output (p = .89), and lactate (p = .67) did not change significantly during H2S exposures in H2S group; all the variables decreased significantly in the control group (p < .01 for all), and p < .01 by comparison with H2S group except for lactate (p = .05). CONCLUSIONS: H2S does not appear to have hypometabolic effects in ambiently cooled large mammals and conversely appears to act as a hemodynamic and metabolic stimulant.     

Tracheal gas insufflation as a lung-protective strategy: physiologic, histologic, and biochemical markers.

OBJECTIVE: Conventional mechanical ventilation in acute lung failure potentiates lung injury, which can be assessed by physiologic, histologic, and biochemical markers. Thus, new ventilation strategies are directed at reducing lung injury. Tracheal gas insufflation has been shown to reduce endotracheal tube prosthetic deadspace and peak inspiratory pressure during conventional mechanical ventilation. Our objective was to use physiologic, histologic, and biochemical markers to test the hypothesis that tracheal gas insufflation in acute lung injury is lung protective. DESIGN: Animal experiment. SETTING: University setting. SUBJECTS: Juvenile rabbits (n = 12; 1.95 +/- 0.1 SE kg). INTERVENTIONS: Rabbits were anesthetized, instrumented, paralyzed, and ventilated with Fio(2) = 1.0. Lung injury was induced with repeated saline lavage (10 mL/kg per lavage until Pao(2) 相似文献   

Interaction between inhaled nitric oxide and intravenous sildenafil in a porcine model of meconium aspiration syndrome

There has been recent interest in the use of the phosphodiesterase-5 inhibitor sildenafil for treating pulmonary hypertension. We examined the interaction between inhaled nitric oxide (iNO) and i.v. sildenafil in 12 piglets with acute pulmonary hypertension and lung injury secondary to meconium aspiration. Six animals (controls) received no intervention after meconium instillation, and six received iNO (20 ppm) from 120 min, with the addition at 240 min of an i.v. sildenafil infusion (2 mg/kg over 2 h). Meconium instillation increased mean pulmonary artery (PA) pressure from 16.0 +/- 3.1 to 24.8 +/- 4.6 mm Hg (p < 0.01) and pulmonary vascular resistance (PVR) from 0.047 +/- 0.008 to 0.089 +/- 0.027 mm Hg. ml(-1). min(-1). kg(-1) (p < 0.01). Oxygenation index increased from 3 +/- 0.8 to 8.3 +/- 3.0 (p < 0.01). There were no further changes beyond 120 min in controls. iNO reduced PA pressure and PVR to baseline values, without influencing oxygenation. The addition of sildenafil further reduced PA pressure, tended to increase the cardiac output, and reduced PVR from 0.049 +/- 0.02 to 0.028 +/- 0.01 mm Hg. ml(-1). min(-1). kg(-1) (p < 0.05). Sildenafil lowered the systemic blood pressure and systemic vascular resistance and produced profound arterial hypoxemia, reducing arterial Po(2) from 69 +/- 23 mm Hg to 49 +/- 15 mm Hg, despite substantial increases first in inspired oxygen fraction and subsequently in mean airway pressures. Consequently, the oxygenation index increased by 13.9 +/- 4.8 (p = 0.01). When given in addition to iNO, sildenafil at a dose of >0.5 mg/kg produced profound pulmonary vasodilation, but this was coupled with an unacceptable deterioration in oxygenation and systemic vasodilation in this model of pulmonary hypertension with acute parenchymal lung disease.     

Inhaled nitric oxide improves oxygenation in very premature infants with low pulmonary blood flow

AIM: Inhaled nitric oxide (iNO) is used to reduce right-to-left extrapulmonary shunting by decreasing pulmonary vascular resistance in term or near-term infants. The objectives of this study were to determine, first, the pulmonary blood flow status of very preterm infants with hypoxaemic respiratory failure, then the response of oxygenation to iNO therapy according to pulmonary blood flow (PBF) and, finally, to verify the lack of adverse side effects of iNO on the ductus arteriosus. METHODS: Infants below 32 wk gestational age (GA) with hypoxic respiratory failure and aAO2 < 0.22 were randomized as the control or iNO group. PBF was evaluated by pulsed Doppler measurement of mean pulmonary blood flow velocity (MPBFV) in the left pulmonary artery. Low PBF (LPBF) was defined as MPBFV < 0.2 m/s. RESULTS: Seventy infants of 23 to 31 wk GA with hypoxic respiratory failure were randomized either to receive or not to receive 5 ppm iNO in addition to optimal care. Twenty-eight infants were diagnosed with LPBF (11/35 in iNO vs 17/35 in the control groups). Thirty minutes after receiving iNO the number of LPBF infants dropped to 8/35. In the iNO group, aAO2 increased significantly from 0.14 +/- 0.05 to 0.24 +/- 0.08 after iNO, but only in the LPBF infants (mean +/- SD; p = 0.027). CONCLUSION: In infants below 32 wk GA with hypoxic respiratory failure, Doppler echocardiographic assessment of LPBF seems to be able to determine which patients are likely to benefit from iNO therapy on systemic oxygenation.     

Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression profiles in tracheal aspirates do not adequately reflect tracheal or lung tissue profiles in neonatal respiratory distress: observations from an animal model.

OBJECTIVE: Matrix metalloproteinase (MMP)/tissue inhibitor of matrix metalloproteinase (TIMP) expression in tracheal aspirates (TA) is commonly assayed to represent the protein profile in the lung. This study tests the hypothesis that the profile of MMPs 2, 7, and 9 and the profile of TIMPs 1 and 2 will be different in TA, tracheal tissue, and lung tissue in neonatal respiratory distress. DESIGN: Interventional laboratory study. SETTING: An academic medical research facility in northeastern United States. SUBJECTS: Oleic acid-injured, spontaneously breathing newborn piglets. INTERVENTIONS: Ten piglets (3-4 days old, 2.4 +/- 0.4 kg) were instrumented, injured by intravenous administration of oleic acid, and supported on continuous positive airway pressure of 2-5 cm H2O, with or without exogenous surfactant, depending on physiologic requirements. MEASUREMENT AND MAIN RESULTS: After 6 hrs, TA, trachea, and lung were obtained for MMP/TIMP analysis by substrate zymography/reverse zymography. TA contained less active (p < .01) and more latent (p < .05) MMP-2 than trachea and lung, and the active/latent ratio was less in TA than in both tissues (p < .01). TA and trachea contained more total (p < .05) and active (p < .01) MMP-9 than did the lung; TA contained more active MMP-9 than trachea (p < .01). MMP-7 was greater in all forms relative to total protein (p < .01) from both tissues compared with TA. Trachea contained more latent MMP-7 than lung (p < .01). TIMP-1 was different across protein sources (p < .01) where TA < trachea < lung. The active MMP-2/TIMP-2 ratio was lower in TA than in lung (p < .01); the MMP-9/TIMP-1 ratio had a significant trend (p < .01) where TA > trachea > lung. CONCLUSIONS: The MMP/TIMP profiles in TA do not adequately represent the profiles in either trachea or lung. Thus, MMP/TIMP profiles from TA are limited and should be interpreted for trends rather than actual tissue levels.     

肺表面活性物质和吸入一氧化氮治疗家兔胎粪吸入性肺损伤

目的　观察在应用肺表面活性物质 (Surf)和吸入一氧化氮 (NO)预防性治疗家兔胎粪吸入性急性肺损伤 (ALI)并机械通气时的疗效。方法　将 3 3只成年家兔随机分为 5组进行治疗 :即对照组 (C ,n =8)、NO组 (n =6)、Surf组 (n =7)、NO +Surf组 (SNO ,n =6)、正常组 (N ,n =6)。前四组用胎粪生理盐水混悬液滴入气道内经机械通气造成ALI并随机分四组治疗 ;N组气道内滴入生理盐水替代 ;NO组连续吸入NO 1× 10 - 6 、10× 10 - 6 、2 0× 10 - 6 、40× 10 - 6 各 1h ,间隔停用 3 0min ;Surf组气道内滴入猪肺Surf10 0mg/kg ;SNO组联合NO吸入及Surf组治疗 ,各组均治疗 6h ,同时测定血气、肺呼吸力学判断疗效。化学发光法检测吸入气NO浓度。结果　在C组胎粪滴入 3 0min后动脉血氧合 (PaO2 /FiO2 )及呼吸顺应性 (DynamicCompliance ,Cdyn)显著变差 ,治疗后血氧合、Cdyn在SNO组显著改善 ,Surf和NO组略有改善。在湿化器前持续接入NO可在供气管道“Y”近端测得较为稳定的吸入NO浓度 ,受呼出气的影响最小 ,( 10～ 2 0 )× 10 - 6 NO吸入有较好的效果。结论　Surf联合NO治疗在有效预防ALI上优于单独应用Surf或NO。从呼吸机供气管路持续接入NO测定到稳定NO浓度与接入气和监测部位有关     

连续性血液透析滤过治疗肠穿孔腹膜炎SIRS幼猪疗效观察

目的：全身炎症反应综合征（SIRS）是各种原因引起多脏器功能障碍综合征的共同通路,目前临床缺乏有效的治疗措施。该研究旨在对肠穿孔腹膜炎诱导的SIRS幼猪行早期连续性血液透析滤过,观察SIRS动物的体温、心率、呼吸、血压、血气分析和外周血细胞计数,为临床治疗提供实验依据。方法：12只上海种小白猪,体重7~9 kg,雌雄不限。随机分为2组：对照组（n=6）;治疗组（n=6,连续性血液透析滤过,CVVHDF）。以盲肠穿孔术诱导SIRS,造模成功后治疗组行CVVHDF 6 h,血流速度20 mL/min,透析液速度600 mL/h,置换液速度300 mL/h,零平衡。于动物基础状态、成模时、成模后2,4,6 h分别记录两组动物的心率、呼吸、血压、体温、外周血细胞计数和血气分析结果。结果：所有动物经造模后均出现心率、呼吸频率上升,血压、动脉血氧分压、白细胞计数下降。成模时对照组动物心率和呼吸增快在6 h内持续保持较高水平;治疗组动物成模2 h后心率下降,6 h后呼吸频率下降与对照组相比差异有显著性,P<0.05。对照组动物成模4 h后平均动脉压下降,与治疗组比较差异有显著性,P<0.05。两组动物成模后动脉血氧分压均较基础状态降低,6 h内对照组动物保持低水平,治疗组动物动脉血氧分压有上升趋势,但组间差异无显著性。实验中动物体温及外周血细胞计数变化组间比较差异无显著性。结论：早期CVVHDF可稳定肠穿孔腹膜炎诱导的SIRS幼猪血流动力学,改善血氧分压,可能对改善疾病预后有益。［中国当代儿科杂志,2007,9（3）：237-240］     

Auto-PEEP effects on respiratory mechanics and blood gases in mechanically ventilated patients

OBJECTIVE: The purpose of this study was to examine the auto-PEEP incidence and magnitude and the relationship between its reductions and changes in respiratory mechanics and gas exchanges in mechanically ventilated patients addmited in an Intensive Care Unit.METHODS: A prospective study was conducted in seventeen infants undergoing mechanical ventilation due to respiratory or neuromuscular diseases. We have measured blood gases, mean airway pressure, tidal volume, compliance, resistance and time constants of the respiratory system and monitored pressure, flow and volume waveforms and pressure-volume and flow-volume loops.RESULTS: Thirteen patients or 76% developed auto-PEEP and the reduction of its magnitude (from 5.4 -/+ 3.2 to 4.1 -/+ 2.6 cmH2O, p<0.01) showed association to mean airway pressure decrease (from 10.2 -/+ 3.1 to 9.3 -/+ 2.3 cmH2O, p<0.01), tidal volume (from 45.3 -/+ 19.1 to 51.3 -/+ 22.9 ml, p<0.01) and corrected compliance increase (1.02 -/+ 1.20 to 1.13 -/+ 1.41 ml/cmH2O/kg, p=0.05). Expiratory resistance remained unchanged (from 15.0 -/+ 8.6 to 15.7 -/+ 9.4 cmH2O/l/sec/kg, p=0.06). Arterial blood gases showed pH increase (from 7.37 -/+ 0.12 to 7.42 -/+ 0.05, p<0.05) and PCO2 and PO2 decrease (from 40.1 -/+ 11.1 mmHg to 33.1 -/+ 7.4 mmHg, p<0.01 and 65.0 -/+ 13.9 to 58.0 -/+ 12.6 mmHg, p<0.01 respectively).CONCLUSIONS: Auto-PEEP reduction was associated with pulmonary mechanics and blood gases improvement. Knowledge of auto-PEEP presence and magnitude allowed to respiratory system compliance and time constants correction, providing accurate index of the pulmonary mechanics.     

Albumin mixed with meconium attenuates pulmonary dysfunction in a newborn piglet model with meconium aspiration

We hypothesized that lipids and bile acids in meconium may induce pulmonary insufficiency in newborns. Because albumin may bind these components we studied the effect of albumin on meconium-induced lung injury in piglets. We measured concentration of FFA in the meconium (110 mg dry weight/mL) and added albumin to provide a molar FFA to albumin ratio of 1:1. Newborn piglets, 0-2 d of age, artificially ventilated and exposed to hypoxemia by ventilation with 8% O2, were randomized to group A receiving meconium (n = 12) or group B receiving meconium + albumin (n = 12), 3 mL/kg intratracheally. The animals were reoxygenated for 8 h. Reoxygenation was started when mean blood pressure was <20 mm Hg or base excess was <-20 mM. Pulmonary function was assessed in parallel with pulmonary hemodynamics. From the start of reoxygenation and the next 8 h we found a significant difference (by ANOVA) between the two groups in oxygenation index (p = 0.005), with an increase from 1.6 +/- 0.2 to 6.1 +/- 6.8 (p = 0.04) in the meconium group and from 1.8 +/- 0.3 to 3.1 +/- 3.1 (NS) in meconium + albumin group. There were also significant differences (by ANOVA) between the groups in favor of the treatment group concerning need of inspired fraction of O2, mean airway pressure, dynamic compliance of the respiratory system, time constant, ventilation index, and pulmonary vascular resistance. In conclusion, albumin given concurrently with meconium significantly reduced detrimental effects of meconium aspiration in the lungs of newborn piglets.     

Partial liquid ventilation versus conventional mechanical ventilation with high PEEP and moderate tidal volume in acute respiratory failure in piglets

This prospective randomized pilot study aimed to test the hypotheses that partial liquid ventilation combined with a high positive end-expiratory pressure (PEEP) and a moderate tidal volume results in improved gas exchange and lung mechanics without negative hemodynamic influences compared with conventional mechanical ventilation in acute lung injury in piglets. Acute lung injury was induced in 12 piglets weighing 9.0 +/- 2.4 kg by repeated i.v. injections of oleic acid and repeated lung lavages. Thereafter, the animals were randomly assigned either to partial liquid ventilation (n = 6) or conventional mechanical ventilation (n = 6) at a fractional concentration of inspired O(2) of 1.0, a PEEP of 1.2 kPa, a tidal volume < 10 mL/kg body weight (bw), a respiratory rate of 24 breaths/min, and an inspiratory/expiratory ratio of 1:2. Perfluorocarbon liquid 30 mL/kg bw was instilled into the endotracheal tube over 10 min followed by 5 mL/kg bw/h. Continuous monitoring included ECG, mean right atrial, pulmonary artery, pulmonary capillary, and arterial pressures, arterial blood gas, and partial pressure of end-tidal CO(2) measurements. When compared with control animals, partial liquid ventilation resulted in significantly better oxygenation with improved cardiac output and oxygen delivery. Dead space ventilation appeared to be lower during partial liquid ventilation compared with conventional mechanical ventilation. No significant differences were observed in airway pressures, pulmonary compliance, and airway resistance between both groups. The results of this pilot study suggest that partial liquid ventilation combined with high PEEP and moderate tidal volume improves oxygenation, dead space ventilation, cardiac output, and oxygen delivery compared with conventional mechanical ventilation in acute lung injury in piglets but has no significant influence on lung mechanics.     

Effects of dexamethasone on meconium aspiration syndrome in newborn piglets.

We examined the effects of dexamethasone on lung function in a piglet model of meconium aspiration syndrome. We induced lung injury in 10 newborn piglets (age 5 +/- 0.2 d) with 4 mL/kg body weight of 20% sterile human meconium in normal saline given via tracheostomy. Ventilator management was aimed at maintaining comparable values of end tidal carbon dioxide, Hb saturation, and arterial blood gases. Lung function was assessed using a BICORE CP100 neonatal monitor. Five piglets received 0.5 mg/kg of dexamethasone 2 and 8 h after meconium administration, whereas control piglets received normal saline at similar times. Ventilator settings, oxygen requirements, and lung compliance were similar between groups at the start of the study. Two hours after the instillation of meconium, there was marked lung dysfunction in both groups as evidenced by increased oxygen requirements [fraction of inspired oxygen (FiO2) 0.98 +/- 0.01 versus FiO2 0.21 +/- 0, p < 0.0001] and reduced lung compliance (0.35 +/- 0.03 versus 0.8 +/- 0.03 mL x kg(-1) x cm(-1) H2O, p < 0.0001). Administration of dexamethasone resulted in lower oxygen requirements (FiO2 0.27 +/- 0.01 versus FiO2 1.0 +/- 0.0, p < 0.00001), lower oxygenation index (2.17 +/- 0.17 versus 22.64 +/- 3.39, p < 0.0001), ventilatory efficiency index (0.30 +/- 0.01 versus 0.07 +/- 0.01, p < 0.0001), and improved lung compliance (0.68 +/- 0.04 versus 0.34 +/- 0.05 mL x kg(-1) x cm(-1) H2O, p < 0.001) compared with the control group. In summary, a two-dose course of 0.5 mg/kg of dexamethasone improved blood gases and lung function in a piglet model of meconium aspiration syndrome.     

Effects of anti-CD18 monoclonal antibody, R15.7, on the cardiopulmonary manifestations of group B streptococcal sepsis in piglets

We hypothesized that anti-CD18 monoclonal antibody, R15.7, a murine IgG(1) antibody which blocks leukocyte-endothelial cell adherence, might ameliorate the cardiopulmonary manifestations of sepsis secondary to group B streptococci (GBS). Twenty-six anesthetized, mechanically ventilated newborn piglets received a continuous infusion of GBS (7.5 x 10(9) cfu/kg/min) and were randomly assigned to a treatment group receiving R15.7 (1 mg/kg i.v.) 15 min prior to GBS infusion or to a control group. Cardiopulmonary measurements, arterial blood gases and peripheral blood leukocytes were obtained over 120 min of R15.7 infusion. GBS infusion caused significant increases in pulmonary artery and systemic arterial blood (Psa) pressures, pulmonary vascular (PVR) and systemic vascular (SVR) resistances, and PVR/SVR ratio with decreases in cardiac output and stroke volume. R15.7-treated piglets maintained significantly higher Psa (p < 0.003), dynamic lung compliance (p < 0.04), PaO2 and pH (p < 0.05), and lower total lung resistance (p < 0.01) and PaCO2 (p < 0.04). A longer median survival time was observed in the treatment group (p < 0.01). These data suggest that administration of a CD18-blocking agent prolongs survival in a young animal model of GBS sepsis, possibly secondary to improved tissue perfusion, lung mechanics and acid-base status.     

A dose response study of inhaled nitric oxide in hypoxic respiratory failure in preterm infants

BACKGROUND: Inhaled nitric oxide (iNO) is used widely in newborn infants with hypoxic respiratory failure, despite the known and theoretical toxicity of iNO, and a relative lack of information about appropriate doses. AIM: To determine whether a dose-response relationship existed for iNO in preterm infants. DESIGN: A four-period, four-dose, cross-over design was used with iNO given for 15 min in a randomised sequence in concentrations of 5, 10, 20 and 40 parts per million (ppm), with a minimum 5 min wash-out period. Data on ventilatory, blood gas and other physiological measurements were recorded before and at the end of each period. The relationship of clinical response with iNO dose and period was analysed using multivariate regression. SUBJECTS: Infants with gestational age < 34 weeks and < 28 days postnatal age with hypoxic respiratory failure were recruited. OUTCOME MEASURE: A clinically significant dose-response was defined as a rise in the post-ductal arterial oxygen tension (PaO(2)) of at least 3 kPa. RESULTS: Thirteen infants were recruited. At trial entry, ten were < 3 days of age; 11 were being treated with high frequency oscillatory ventilation; median (inter-quartile range) gestational age 27 (25-29) weeks; birthweight 983 (765-1120) g; oxygenation index 27.1 (21.8-28.8). Six infants (46%) showed a clinically significant response. After adjusting for period and patient effect, no evidence for an overall dose effect was identified (likelihood ratio test, p=0.34). CONCLUSION: No evidence of a dose-response relationship with iNO was found in this study of very preterm infants with respiratory failure.     

吸入一氧化氮对感染性急性肺损伤时红细胞变形能力的影响

目的 研究吸入一氧化氮(NO)对红细胞变形能力的影响及其可能机制.方法 将3～4周龄健康雄性幼猪30只麻醉后经口气管插管进行机械通气,随机分为4组.(1)正常组(C,n=6)单纯机械通气;(2)正常幼猪加吸入NO(CNO,n=4);(3)模型组(M,n=10)单纯机械通气;(4)模型制备加吸入N0(MNO,n=10).M和MNO组动物经腹腔注射标准大肠杆菌诱发急性肺损伤(ALI),C及CNO组用无菌生理盐水替代.MNO组出现ALI后进行吸入NO(10×10-6),治疗24h,CNO组则机械通气4 h后(0 h)开始吸入NO并维持24 h.在实验基础状态、ALI时(0 h)、ALI后12以及24 h测血细胞比容、全血黏度、红细胞膜Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶活性及红细胞内丙二醛(MDA)浓度.结果 CNO组吸入NO后12、24 h高切率下血液黏度(反映红细胞变形能力)、红细胞膜Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶活性及红细胞内MDA浓度变化不大.动物出现ALI时其红细胞变形能力降低,红细胞膜Ca2+-Mg2+-ATP酶、Na+-K+-ATP酶活性均下降,红细胞内MDA浓度升高(P＜0.05).MNO组在吸入NO 12 h时红细胞变形能力改善,红细胞膜Ca2+-Mg2+-ATP酶、Na+-K+-ATP酶活性均较M组高(P＜0.05),红细胞内MDA浓度则低于M组(P＜0.05);但这些参数在吸入NO 24 h与C组比较差异均无显著性(P＞0.05).结论 ALI时红细胞变形能力显著下降,可以因吸入NO而改善,但作用不持久.     

肺复张策略救治急性肺损伤幼猪的实验研究

目的：通过急性肺损伤（ALI）幼猪模型,研究肺复张策略（RM）的可行性和有效性,并探讨其对损伤后肺组织修复的影响。方法：健康幼猪12只,注射内毒素（LPS）成模后,随机分为常规潮气量通气组（CON组）和小潮气量联合RM通气组（RM组）,观察8 h,动态监测血液动力学、肺动态顺应性及血气分析指标,测定血浆、肺泡灌洗液中转化生长因子（TGF-β1）浓度,实时荧光定量PCR法检测TGF-β1在肺组织中的mRNA表达水平,并观察肺组织的病理学改变。结果：两组幼猪的心输出量和外周血管阻力指标差异无统计学意义;而RM组的血管外肺水指数在成模6 h以后,肺血管通透性指数于成模8 h时均较CON组明显下降（P＜0.05）;RM组的肺动态顺应性明显高于同时间点的CON组（P＜0.05）;RM组PaO2/FiO2值于成模2 h后明显高于CON组,而且RM组的肺泡-动脉氧分压差在成模2 h后即明显下降（P＜0.05）;RM组血浆、肺泡灌洗液中TGF-β1浓度及其在肺组织中的mRNA表达水平均低于相应CON组;RM组的肺泡扩张度明显高于CON组,而肺损伤评分明显下降（P＜0.05）。结论：RM可以改善ALI幼猪的气体交换和肺动态顺应性,且安全有效,能够扩张肺泡并减轻肺损伤程度,有助于改善损伤后的肺修复过程。     

Contribution of pulmonary surfactant with inhaled nitric oxide for treatment of pulmonary hypertension

BACKGROUND: Combined therapy of inhaled nitric oxide (iNO) with pulmonary surfactant replacement was reported to improve oxygenation in patients or animal models of persistent pulmonary hypertension of the newborn with pulmonary surfactant deficiency lung. To evaluate the potential of iNO for the treatment of persistent pulmonary hypertension of the newborn, pulmonary arterial pressure (PAP) was measured during iNO before and after pulmonary surfactant replacement in an animal model of pulmonary hypertension with surfactant deficiency. METHODS: Seven newborn piglets were injected with L-nitro-arginine-methylester to produce an animal model of pulmonary hypertension. After PAP increased, iNO (30 p.p.m.) was introduced. Then iNO was stopped, and animals were subjected to lung lavage with saline. After recording the effect of iNO, all animals then received exogenous pulmonary surfactant installation. After surfactant treatment, iNO was again introduced. RESULTS: Pulmonary arterial pressure and systemic arterial pressure were increased significantly by >30% after infusion of L-nitro-arginine-methylester. During iNO only PAP was reduced significantly. Respiratory system compliance decreased significantly after lung lavage, and increased significantly after pulmonary surfactant replacement with concomitant increase of PaO2. In contrast, significant reduction of PAP with iNO before and after pulmonary surfactant replacement were also observed. The reduction ratios of PAP under each condition were 75.2 +/- 7.4%, 81.3 +/- 3.1%, and 79.1 +/- 5.3%, respectively (not significant among conditions). CONCLUSION: These results suggest that iNO is still a potent pulmonary arterial vasodilator even under pulmonary surfactant deficiency in an animal model of pulmonary hypertension.     

Spontaneous breathing during partial liquid ventilation in animals with meconium aspiration

Partial liquid ventilation (PLV) has been shown to improve gas exchange in paralyzed animals and humans with lung disease. The present study tests the hypothesis that PLV improves gas exchange in spontaneously breathing animals with meconium aspiration supported by proportional assist ventilation. Twenty-five adult anesthetized intubated rabbits with experimental meconium aspiration were randomized to gas ventilation (GV) or PLV while being supported by proportional assist ventilation. Minute ventilation, tidal volume, respiratory rate, mean airway pressure, heart rate, and mean arterial and pulmonary arterial pressure were recorded continuously. Every 30 min, arterial blood gases were obtained, and lung compliance, airway resistance, work of breathing, and cardiac output were measured. Animals were sacrificed after 5 h to obtain lung histology. More PLV animals survived until the end of the study period. PaO(2) (14.5 +/- 4.5 versus 25.6 +/- 6.7 kPa; p < 0.01; GV versus PLV) and lung compliance (4.3 +/- 0.4 versus 6.1 +/- 1.2 mL.kPa(-1).kg(-1); p < 0.001) were improved during PLV, resulting in a lower work of breathing (5.3 +/- 2.8 versus 3.5 +/- 1.5 mL.kPa.kg(-1); p < 0.05) and less need for ventilatory support. Minute ventilation and respiratory rate were higher during GV versus PLV, resulting in a slightly lower PaCO(2) (3.9 +/- 0.5 versus 4.5 +/- 0.7 kPa; p < 0.05). Histologic evaluation showed more atelectasis, inflammatory changes, and hemorrhage in GV animals. Other parameters measured were similar. We conclude that PLV improves oxygenation, lung compliance, and survival and results in less lung injury in spontaneously breathing animals with meconium aspiration when supported by proportional assist ventilation.     

Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema.

We studied 50 preterm infants who had multiple or traumatic endotracheal intubations, or whose duration of endotracheal intubation was > or = to 14 days, and who were considered at high risk for airway edema. These infants were enrolled in a prospective, randomized, controlled clinical trial to assess whether prophylactic dexamethasone therapy would be effective in the prevention of postextubation stridor and respiratory distress. At study entry, both groups had similar weights, postnatal ages, methylxanthine use, ventilator settings, blood gas values, and pulmonary function test results (dynamic compliance, total respiratory resistance, tidal volume, peak-to-peak transpulmonary pressure, minute ventilation, and peak inspiratory and expiratory flow rates). Patients underwent blood gas studies, physical examinations, and pulmonary function testing at baseline (4 hours before extubation) and again 2 to 4 hours and 18 to 24 hours after extubation. Twenty-seven infants received dexamethasone, 0.25 mg/kg per dose, at baseline, and then every 8 hours for a total of three doses; 23 infants received saline solution at corresponding times. Eighteen to twenty-four hours after extubation, total pulmonary resistance increased by 225% from baseline in the control group compared with 33% in the dexamethasone group (p < 0.006), and the dexamethasone group had a greater tidal volume, a greater dynamic compliance, and a lower arterial carbon dioxide pressure. Of 23 control infants, 10 had postextubation stridor compared with 2 of 27 dexamethasone-treated patients (p < 0.006). Of the 23 control patients, 4 required reintubation compared with none of the treated group (p < 0.05). We conclude that the prophylactic use of corticosteroids for the prevention of postextubation stridor and respiratory distress is efficacious in low birth weight, high-risk preterm infants.     

Dose response to aerosolized perflubron in a neonatal swine model of lung injury

Aerosolized perfluorocarbon (PFC) improves gas exchange, lung mechanics, and pulmonary artery pressure. The objective of this intervention was to study the dose-response effect to aerosolized perfluorooctylbromide (PFOB; perflubron, LiquiVent, Alliance Pharmaceutical Corp.) in surfactant-depleted piglets. After induction of lung injury by saline lavage, 25 newborn piglets were randomly assigned to receive 0, 1.25, 2.5, 5.0, or 7.5 mL/kg aerosolized PFOB per hour. A 2-h therapy period was followed by a 3-h observation period. In all animals, respiratory support was performed with intermittent mandatory ventilation. After aerosol treatment and 3 h of observation, arterial oxygen pressure was similarly improved in the 2.5-, 5.0-, and 7.5-mL. kg(-1). h(-1) aerosol-PFOB groups and higher compared with the 1.25-mL. kg(-1). h(-1) aerosol-PFOB (P < 0.01) and the control groups (P < 0.001). Compared with the control group, arterial carbon dioxide pressure was significantly reduced with 2.5-, 5.0-, and 7.5-mL. kg(-1). h(-1) aerosol-PFOB (P < 0.001). Treatment with 1.25 mL. kg(-1). h(-1) aerosol-PFOB did not significantly affect arterial carbon dioxide pressure. The 20% terminal dynamic compliance/dynamic compliance was significantly improved in the groups that received 2.5, 5.0, and 7.5 mL. kg(-1). h(-1) aerosol-PFOB compared with control animals. Mean pulmonary artery pressure was lower after therapy with 5.0 and 7.5 mL. kg(-1). h(-1) aerosol-PFOB (P < 0.01) than in the control group. IL-1beta gene expression in lung tissue was significantly reduced with PFOB 1.25 mL. kg(-1). h(-1). In summary, aerosolized PFOB improved terminal dynamic compliance, pulmonary gas exchange, and pulmonary artery pressure in a dose-dependent manner. In terms of oxygenation and lung mechanics, the optimum dose was between 2.5 and 5 mL. kg(-1). h(-1).