不同压力呼气末正压对单肺通气时肺内分流及氧合的影响

目的观察单肺通气(OLV)期间通气侧肺实施不同大小的呼气末正压通气(PEEP)对肺内分流及氧合的影响。方法45例ASAⅠ～Ⅱ级择期在全麻下行肺叶切除手术病人,随机分为3组,每组15例。A组为不采用PEEP的OLV对照组;B组为OLV PEEP(5cmH2O)组;C组为OLV PEEP(8cmH2O)组。各组病例于OLV前、OLV后30min、OVL结束、恢复双肺通气后30min进行动脉血气分析,根据公式计算肺内分流率(QS/QT)。结果OVL30min及OVL结束时,B、C两组的PaO2较A组高,QS/QT较A组低(P<0.05);B、C两组各时点参数比较差异无统计学意义(P>0.05)。结论OVL期间通气侧肺实施5cmH2O及8cmH2O的PEEP可明显提高PaO2,减少肺内分流;5cmH2O的PEEP有利于手术操作,临床实用价值更高。     

A rat model of acute respiratory distress syndrome (ARDS): Part 1. Time dependency of histological and pathological changes

The time course of histopathological changes in a rat lung lavage model of the acute respiratory distress syndrome (ARDS) was analyzed by sacrificing animals 10, 30, 60, 180, and 210 min after the last lung parenchyma lavage which was performed with physiological saline solution. This lavage depleted the lung from its natural surfactant resources leading into a pathophysiological cascade similar to that of the acute respiratory distress syndrome. Tracheotomized rats (12 animals per time point) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths/min, inspiration-expiration ratio of 1:2, peak inspiratory pressure of 28 cm H2O at positive end-expiratory pressure (PEEP) of 8 cm H2O. During the whole experimental period, the ventilation was not changed. Blood gases (partial arterial oxygen pressures [PaO2, mmHg] and partial arterial carbon dioxide pressures [PaCO2, mmHg]) were estimated before, directly after, and 10, 30, 60, 90, 120, 150, 180, and 210 min after the last lavage. For grading lung lavage-induced histopathological changes associated with the time-dependent development of ARDS, slides were coded and evaluated without any knowledge of the sacrifice time. A semiquantitative grading was performed with respect to the severity of the following parameters: hyaline membrane formation (HM), interstitial and intraalveolar edema edema (E), and margination and infiltration of polymorphonuclear neutrophil leukocytes (PMNL) into the lung alveoli. The severity of these parameters showed a time-dependent increase after the last lavage. This was accompanied by a time-dependent decrease in partial arterial oxygen pressure (PaO2) values during the early postlavage period (up to 30 min). Thereafter, PaO2 levels remained fairly stable. The severity of intraalveolar and/or perivascular hemorrhages within the lung was not time dependent. The rat lavage model shows similarities to the pathophysiological sequelae occuring during the acute phase of the acute respiratory distress syndrome in humans. Most of the characteristic pathognomic histological changes seen in humans can be observed in this lung lavage model. This ARDS model is brief and easy in its experimental design, showed a good and homogeneous reproducibility of pathophysiological and histopathological parameters, and is therefore a useful model to estimate the influence of therapeutic pharmacological treatments of ARDS.     

Protein- and lipid modification of natural bovine surfactant. Effects in experimental lung failure with special consideration of the response in neonates

Surfactant therapy does not lead to a uniform, optimal and sustained effect on gas exchange in neonatal respiratory distress syndrome (RDS) and acute respiratory distress syndrome (ARDS). The aim of the present study therefore was to compare the effects of a lipid-enriched and protein-modified natural surfactant preparations with a licensed, clinically used bovine surfactant preparation - SF-Ril (Alveofact). METHODS: SF-Ril was enriched with phosphatidylglycerol, sphingomyeline, phosphatidylethanolamine plasmalogen, phosphatidylethanolamine. Furthermore, SF-Ril was modified with increased surfactant protein B (SP-B)/surfactant protein C (SP-C) content and finally a mercaptoethanol (ME) treated preparation for breaking the sulfhydril bondage of SP-B/SP-C by chemical reduction in methylene chloride using ME was developed. Finally ME was removed by vacuum extraction. These modified surfactants were tested at a dosage of 100 mg/ kg each in a model of respiratory failure induced by lung lavage in male adult rats and compared with SF-Ril at an identical dosage. Mechanical ventilation was standardised with fraction of inspiratory oxygen (FiO2) 1.0 and time-cycled pressure limited ventilation 16/0.8 cmH2O before and 26/6 cmH2O (peak inspiratory pressure/positive endexpiratory pressure) after lung lavage (target arterial oxygen pressure [pa02] < 100 mmHg), respiratory rate 36/min, inspiration/expiration time ratio 1:2. RESULTS: During the observation period of 120 min, the sphingomyeline substituted and protein-modified (ME reduced) surfactant preparations exerted improved and sustained oxygenation compared with SF-Ril. Similar effects were observed for tidal volumes. All other preparations were equal or inferior to SF-Ril in our model. CONCLUSION: For the development of surfactant preparations less prone for inactivation the above mentioned data may provide useful information, provided they can be confirmed in further investigations employing other alternative models.     

呼气末正压通气对急性呼吸窘迫综合征患者氧利用率的影响

目的探讨呼气末正压通气（PEEP）对急性呼吸窘迫综合征（ARDS）患者氧利用率（O2UC）的影响。方法选择28例ARDS机械通气患者,放置中心静脉导管,依次调节PEEP为0、5、10、15和20cmH2O五种不同压力水平,分别采动静脉血查血气并计算O2UC,记录心率及平均动脉血压（MBP）等变化。同时抽取30例健康人动静脉血（1次）查血气计算O2UC作为对照。结果（1）ARDS患者五种不同水平的PEEP,其O2UC与健康人O2UC相比均明显下降（P〈0．05或P〈0．01）。（2）在PEEP为15cmH2O时,O2UC值显著低于PEEP为0cmH2O时的02UC（P〈0．05）;PEEP为20cmH2O时,O2UC则非常显著地降低（P〈0．01）。PEEP为5、10cmH2O时,O2UC差异无统计学意义（与PEEP为0cmH2O时比较,P〉0．05）。（3）当PEEP在15cmH2O及20cmH2O时,MBP明显下降（P〈0．05或P〈0．01）,HR却明显上升（P〈0．05或P〈0．01）。结论过高PFEP会导致ARDS患者氧利用率的进一步下降,不能真正纠正患者体内组织细胞的缺氧状态,必须寻找最佳PEEP,并适当增加血容量及有效心输出量,才能真正改善患者的缺氧状态。     

压力控制肺复张术对老年患者腹腔镜肝切除术后肺部并发症(PPCs)的影响

目的 探讨压力控制肺复张术对老年患者腹腔镜肝切除术后肺部并发症(PPCs)的影响.方法 选择择期全身麻醉下行腹腔镜肝切除术的老年患者46例,年龄61～78岁,ASAⅡ～Ⅲ级,随机分为A组和B组,每组23例.A组患者在手术中常规控制呼吸,B组在手术过程中每隔1 h 25 cmH2O(1 cmH2O=98 Pa)涨肺1 min;两组患者在手术过程中其他麻醉处理均相同.记录麻醉前(T0)、拔管后(T1)、术后4h (T2)、术后24h (T3)患者的动脉血气分析结果(PaO2、PaCO2),于术后4h行B超检查有无肺不张,术后24 h拍床旁胸片.结果 与A组比较,B组T1、T2及T3 PaO2有所升高(P＜0.05),PaCO2下降(P＜0.05).A组术毕4h肺部B超显示肺不张发生9例(9/23),B组2例(2/23),B组肺不张发生率明显降低(P＜0.05).术后24h床边胸片显示,A组3例(3/23)发生肺部炎症,B组0例(0/23),B组肺部炎症发生率明显降低(P＜0.05).结论 压力控制肺复张术可以减少老年患者腹腔镜肝切除术后肺部并发症(PPCs)的发生.     

呼气末正压对不同肺部病变重症患者腹内压的影响

目的 探讨呼气末正压(PEEP)对不同肺部病变重症患者腹内压(IAP)的影响.方法 选择2012年1月至2016年12月本院重症医学科进行机械通气的重症患者72例,按照肺部病变分为慢性阻塞性肺疾病(COPD)组、急性呼吸窘迫综合征(ARDS)组及无胸肺部疾患组各24例,观察患者在平卧位时PEEP分别为0、3、6、9、12和15 cmH2O(1 cmH2O=0.098 kPa)条件下的IAP、肺顺应性(CL)、总顺应性(CT)及胸廓顺应性(CTH)的变化,并分析IAP与PEEP、CL、CT、CTH的关系.结果 PEEP对不同肺部病变重症患者IAP的影响:ARDS组＜无胸肺部疾患组＜COPD组(P＜0.05);各组患者肺顺应性:ARDS组＜无胸肺部疾患组＜ COPD组(P＜0.05).相关分析显示,IAP与PEEP存在明显的线性相关(r=0.92,P＜0.01),IAP与CL、CT、CTH存在明显的线性相关(r=0.83、0.64、-0.56,P均＜0.05).结论 不同肺部病变状态下PEEP对IAP的影响不同,其中COPD患者影响较大,而ARDS患者影响较小;影响的大小与肺顺应性大小一致.     

A rat model of acute respiratory distress syndrome (ARDS) Part 2, influence of lavage volume, lavage repetition, and therapeutic treatment with rSP-C surfactant

The influence of lavage volume, and lavage repetition with physiological saline solution (groups 1-3: 3x4, 4x4, 5x4, groups 7-9: 3x8, 5x8, 7x8, mL per animal) was studied in a rat lung lavage model of the acute respiratory distress syndrome (ARDS). Anesthetized and tracheotomized rats (12 rats/group) were pressure-controlled ventilated with 100% oxygen at a respiratory rate of 30 breaths/min, inspiration: expiration ratio of 1:2, peak inspiratory pressure of 28 cm H2O at positive end-expiratory pressure of 8 cm H2O during the whole experimental period. To investigate the influence of therapeutic treatment, a recombinant surfactant protein C (rSP-C) containing surfactant was used. Therefore, rats which received a lavage of 4x4 mL per animal (groups 4 to 6) or 7x8 mL per animal (groups 10-12) were treated intratracheally with surfactant doses of 12.5, 25, or 100 mg phospholipids (PL) per kg body weight (bw). In all groups, partial arterial oxygen pressures (PaO2, mm Hg) and partial arterial carbon dioxide pressures (PaCO2, mm Hg) were determined 30 min before, directly after, and 5, 30, 60, 90, 120, 150, 180, and 210 min after the last lavage. Additionally, animals were euthanized 210 min after the last lavage for semiquantitative histopathological grading of coded lung slides. Grading was performed with respect to the severity of hyaline membrane formation (HM), margination and infiltration of polymorphonuclear neutrophil leukocytes (PMNL) into the lung alveoli and interstitial and intraalveolar edema (E). The intrapulmonary distribution of intratracheally applied rSP-C was estimated in selected lung slides stained with polyclonal anti-rSP-C antibody and was compared to unlavaged control rats and unlavaged rats which received 100 mg/kg bw rSP-C. The repetitive lavage depleted the lung from its natural surfactant resources leading to a pathophysiological cascade similar to that of the acute respiratory distress syndrome. PaO2 levels and HM formation showed a lavage-induced decrease. Both changes were significantly dependent on the repetition and volume of the lavage; however, the parameters PMNL and E did not show such a dependence. Treatment with rSP-C surfactant significantly improved oxygenation and reduced HM-formation in a dose-dependent manner independent from the lavage volume. All doses of rSP-C surfactant showed no clear influence on the parameters PMNL and E independently from the lavage volume. In lavaged rat lungs (ARDS-model), the exogenously applied rSP-C was distributed homogeneously along the alveolar lining. Unlavaged rats that received a similar dose of rSP-C showed a marked inhomogeneous extracellular distribution, mainly associated with larger bronchi, while the type II pneumocytes were stained positively in unlavaged control and unlavaged rSP-C treated rats. Conclusion: This model mimics very closely the wide spectrum of the clinical situation of human acute lung injury (ALI) because the variation of lavage volume and repetition lead to reproducible different severity grades and states of ALI. The significant reduction of pathognomic changes due to treatment with rSP-C surfactant showed that this is a useful model to estimate the influence of therapeutic concepts in ALI and ARDS.     

Dexamethasone enhances the activity of rSP-C surfactant but not of exosurf in a rat model of the acute lung injury

The possible enhancement of surfactant activity by pretreatment with a glucocorticosteroid (dexamethasone) was investigated in a rat lung lavage model of acute lung injury. Animals received a dose of dexamethasone (10 mg/kg i.p.) prior to the protein-free surfactant preparation Exosurf (pure phospholipids containing surfactant, Wellcome GmbH, Burgwedel, Germany) and a rSP-C based surfactant, respectively. Both surfactants were intratracheally instilled at doses of 25 and 100 mg phospholipids per kg body weight and were compared with pretreatment with dexamethasone at each dose level. These groups were also compared with untreated controls and to pretreatment with dexamethasone alone with respect to improvements in oxygenation, to inhibition of infiltration of polymorphonuclear neutrophil leukocytes (PMNL) and to influence formation of hyaline membranes. Dexamethasone alone had no influence on the reduced PaO(2) but reduced the infiltration of PMNL and the formation of hyaline membranes. Dexamethasone improved the oxygenation at both doses of rSP-C surfactant. At the low dose of rSP-C surfactant there were additional effects detectable with regard to histopathologic improvements. In contrast, dexamethasone had no additional effect on oxygenation and formation of hyaline membranes when combined with Exosurf. Only the infiltration of PMNL was decreased by combined treatment with dexamethasone and Exosurf. The effect was comparable to that of pretreatment with dexamethasone alone. In this animal model, pretreatment with dexamethasone showed additional effects on rSP-C surfactant that were superior to each treatment alone. From the comparison of rSP-C surfactant with the synthetic surfactant preparation Exosurf, we conclude that the activity of Exosurf cannot be improved substantially by additional pretreatment with drugs like glucocorticosteroids.     

术中不同时期呼气末正压通气对全身麻醉老年患者血气指标和肺顺应性的影响

目的 探讨术中低潮气量复合不同时期呼气末正压通气(PEEP)的保护性肺通气策略对开腹手术全身麻醉老年患者动脉血气分析指标和肺顺应性的影响. 方法 选择接受开放性腹部手术的老年全身麻醉患者60例,随机分为常规通气组、中期PEEP组和后期PEEP组.常规通气组未复合PEEP,中期PEEP组在手术开始后1 h 复合PEEP,后期PEEP组在拔管前1h复合PEEP,各组PEEP设定为10cmH2O,持续1h.3组均采用间歇性正压通气(IPPV)模式,潮气量为6mL/kg,吸呼比为1∶1.5~2,调节呼吸频率,维持呼气末二氧化碳分压(PETCO2) 在35~45mmHg(1mmHg=0.133kPa).分别于术前、术后1h、术后24h抽取动脉血行血气分析,并记录气管插管后30min、术中90min和拔管前30min的潮气量、PEEP值、气道峰压(Ppeak),计算肺顺应性(CL). 结果 与术前比较,术后1h各组PaCO2明显升高(P<0.05),常规通气组和后期PEEP组氧合指数(OI)明显降低(P<0.05),常规通气组和中期PEEP组肺泡-动脉氧分压差(A-aDO2)明显升高(P<0.05);与术后1h比较,术后24h中期PEEP组PaCO2明显降低(P<0.05),常规通气组OI明显升高(P<0.05),常规通气组和中期PEEP组A-aDO2明显下降(P<0.05),其余差异无统计学意义(P>0.05). 结论 低潮气量复合术中1h PEEP或拔除气管导管前1h复合PEEP均能改善术后血气指标,前者可以改善术后1h和术后24h的氧合功能.     

小剂量糖皮质激素联合小潮气量、肺复张在重症肺炎肺损伤患儿中的应用

目的:观察小剂量糖皮质激素联合小潮气量、肺复张(RM)治疗重症肺炎肺损伤患儿的临床有效性及安全性。方法:入我院PICU 符合重症肺炎肺损伤患儿42例,随机分为试验组和对照组各21例,所有入选患儿均给予常规治疗、小剂量糖皮质激素,试验组入院24 h内给予小潮气量(VT:6~8 mL/kg)机械通气和RM,对照组只给予机械通气(VT:8~10 mL/kg)。分析两组患儿血流动力学、呼吸力学、血气变化、预后及并发症。结果:试验组患儿在小剂量糖皮质激素、小潮气量基础上共进行RM操作73例次, RM后5 min、15 min、60 min气道峰压、呼吸频率、呼气末压力、吸气氧体积分数、平均气道压水平均低于RM前(P<0.05);呼吸频率、平均动脉压RM前后比较差异无统计学意义(P>0.05);两组血气分析均较通气前改善(P<0.05);通气后两组患儿PaO2 / FiO2、肺动态顺应性、呼气功比较差异有统计学意义(P<0.05);试验组机械通气时间、吸氧时间、住院时间均较对照组短,并发症较对照组减少(P<0.05)。结论:小剂量糖皮质激素联合小潮气量、RM可以改善重症肺炎肺损伤患儿氧合功能,提高患儿肺的顺应性,患儿耐受性良好,能缩短患儿机械通气时间、氧暴露时间、住院时间,减少不良反应。     

Acute ozone-induced lung injury in rats: structural-functional relationships of developing alveolar edema.

As part of a study on the effects of acute ozone stress on the lung surfactant system, we correlated morphometric, biochemical, and functional indices of lung injury using male rats exposed to 3 ppm ozone for 1, 2, 4, and 8 hr. Evaluation of lung mechanics, using the Pulmonary Evaluation and Diagnostic Laboratory System, revealed a significant decrease in dynamic lung compliance (ml/cmH2O/kg) from a control value of 0.84 +/- 0.02 (SEM) to 0.72 +/- 0.04 and 0.57 +/- 0.06 at 4 and 8 hr, respectively. At 2 hr there was a transient increase in PaO2 to 116 torr (control = 92 torr) followed by a decrease at 4 hr (65 torr) and 8 hr (55 torr). Morphometry of lung tissue, fixed by perfusion of fixative via the pulmonary artery at 12 cm H2O airway distending pressure, demonstrated an increase in the area of the intravascular compartment at 8 hr, in association with a 65 and 39% replacement of the alveolar area by fluid in ventral and dorsal lung regions, respectively. There was a positive correlation (r = 0.966) between alveolar edema and transudated proteins in lavage fluid. A stepwise multiple regression model, with edema as the dependent variable, suggested that pulmonary vasodilatation, hypoxemia, and depletion of surfactant tubular myelin in lavage fluid were indices for predicting alveolar edema. In a second model, with lavage protein concentration as the dependent variable, decreasing dynamic compliance and hypoxemia were predictors of progressive, intraalveolar transudation of plasma proteins. The above structural-functional relationships support the concept that ozone-induced high-protein alveolar edema is pathogenetically linked to pulmonary hyperemia, deficiency of surfactant tubular myelin, and associated lung dysfunctions.     

Inhalation of the endothelin-A receptor antagonist LU-135252 at various doses in experimental acute lung injury

We studied the effects of the inhaled endothelin-A receptor antagonist LU-135252 at different doses on hemodynamics and gas exchange in an animal model of acute lung injury. Thirtysix piglets (27 +/- 1 kg) were anesthetized, mechanically ventilated (FiO2 1.0), and surfactant-depleted by repeated lung lavage. The animals were randomly assigned to receive either nebulized LU- 135252 for 30 minutes at a dose of 0.3 mg/kg (n = 12), or at a dose of 3.0 mg/kg (n = 12); n = 12 animals received no further treatment (Controls). Induction of acute lung injury decreased PaO2 from 566 +/- 8 mmHg to 53 +/- 2 mmHg (mean +/- SEM) and increased intrapulmonary shunt (QS/QT) from 13 +/- 1% to 57 +/- 2%. Inhalation of LU-135252 at either dose induced a significant and sustained increase in PaO2 (0.3 mg/kg: 349 +/- 39 mmHg; 3.0 mg/kg: 219 +/- 40 mmHg), and a significant decrease in QS/QT (0.3 mg/kg: 19 +/- 2%; 3.0 mg/kg: 27 +/- 3%) when compared with Controls (PaO2: 50 +/- 3 mmHg, QS/QT: 50 +/- 5%) (P < 0.05; values at 4 hours). Mean pulmonary artery pressure in LU-135252-treated animals (0.3 mg/kg: 31 +/- 2 mmHg; 3.0 mg/kg: 30 +/- 1 mmHg) was significantly lower than in Controls (40 +/- 2 mmHg), while there were no differences in mean arterial pressure and cardiac output. We conclude that inhalation of LU-135252 at either dose improved gas exchange and hemodynamics comparably, indicating that the lower dose was already sufficient to block the majority of endothelin-A receptors in ventilated regions of the injured lung.     

Cardiopulmonary haemodynamics in lambs during induced capillary leakage immediately after preterm birth

1. Early postnatal events might play a critical role in the development of cardiorespiratory diseases of prematurity. Although the exact mechanism is unknown, capillary leakage resulting in increased interstitial fluid volume has been postulated to play a critical role. We investigated the effects of capillary leakage, induced by a volume load, on cardiopulmonary and systemic haemodynamics immediately after preterm delivery. 2. Fetal sheep were instrumented at 129 days gestation, delivered and ventilated. After 15 min, lambs in the volume load group received intravenous saline (50 mL/kg) infused over 10 min; control lambs received no infusion. At 30 min, lambs underwent a pulmonary challenge by increasing positive end-expiratory pressure (PEEP) by 2 cmH(2)O every 10 min to 10 cmH(2)O, with similar decrements back to baseline PEEP. Pulmonary blood flow (PBF) and arterial pressures were recorded in real-time and cardiovascular variables were measured by Doppler echocardiography. 3. Total protein concentration in the bronchoalveolar-lavage fluid was higher in volume load lambs compared with controls, and histological interstitial fluid retention was evident in volume load lambs, both indicative of capillary leak. PBF increased immediately after the volume load, but PBF, pulmonary and systemic arterial pressures, and oxygenation all deteriorated during the PEEP challenge compared with controls, coinciding with an increase in downstream pulmonary resistance. Three of six volume load lambs had pulmonary haemorrhage, which was not observed in control lambs. 4. Capillary leakage had moderate effects, but subsequent high levels of PEEP had significant negative effects on cardiopulmonary and respiratory function in preterm lambs. Capillary leakage might contribute to postnatal cardiopulmonary failure in preterm infants.     

Exogenous pulmonary surfactant as a drug delivering agent: influence of antibiotics on surfactant activity.

1. It has been proposed to use exogenous pulmonary surfactant as a drug delivery system for antibiotics to the alveolar compartment of the lung. Little, however, is known about interactions between pulmonary surfactant and antimicrobial agents. This study investigated the activity of a bovine pulmonary surfactant after mixture with amphotericin B, amoxicillin, ceftazidime, pentamidine or tobramycin. 2. Surfactant (1 mg ml-1 in vitro and 40 mg ml-1 in vivo) was mixed with 0.375 mg ml-1 amphotericin B, 50 mg ml-1 amoxicillin, 37.5 mg ml-1 ceftazidime, 1 mg ml-1 pentamidine and 2.5 mg ml-1 tobramycin. Minimal surface tension of 50 microliters of the mixtures was measured in vitro by use of the Wilhelmy balance. In vivo surfactant activity was evaluated by its capacity to restore gas exchange in an established rat model for surfactant deficiency. 3. Surfactant deficiency was induced in ventilated rats by repeated lavage of the lung with warm saline until PaO2 dropped below 80 cmH2O with 100% inspired oxygen at standard ventilation settings. Subsequently an antibiotic-surfactant mixture, saline, air, or surfactant alone was instilled intratracheally (4 ml kg-1 volume, n = 6 per treatment) and blood gas values were measured 5, 30, 60, 90 and 120 min after instillation. 4. The results showed that minimal surface tensions of the mixtures were comparable to that of surfactant alone. In vivo PaO2 levels in the animals receiving ceftazidime-surfactant or pentamidine-surfactant were unchanged when compared to the surfactant group. PaO2 levels in animals receiving amphotericin B-surfactant, amoxicillin-surfactant or tobramycin-surfactant were significantly decreased compared to the surfactant group. For tobramycin it was further found that PaO2 levels were not affected when 0.2 M NaHCO3 (pH = 8.3) buffer was used for suspending surfactant instead of saline. 5. It is concluded that some antibiotics affect the in vivo activity of a bovine pulmonary surfactant. Therefore, before using surfactant-antibiotic mixtures in clinical trials, interactions between the two agents should be carefully evaluated.     

Comparison of rSP-C surfactant with natural and synthetic surfactants after late treatment in a rat model of the acute respiratory distress syndrome

1. In a previous paper we showed that an SP-C containing surfactant preparation has similar activity as bovine-derived surfactants in a rat lung lavage model of the adult respiratory distress syndrome. In this study surfactant was given ten minutes after the last lavage (early treatment). In the present investigation we were interested how different surfactant preparations behave when they are administered 1 h after the last lavage (late treatment).
2. Four protein containing surfactants (rSP-C surfactant, bLES, Infasurf and Survanta) were compared with three protein-free surfactants (ALEC, Exosurf and the phospholipid (PL) mixture of the rSP-C surfactant termed PL surfactant) with respect to their ability to improve gas exchange in this more stringent model when surfactant is given one hour after the last lavage. For better comparison of the surfactants the doses were related to phospholipids. The surfactants were given at doses of 25, 50 and 100 mg kg⁻¹ body weight. The surfactants were compared to an untreated control group that was only ventilated for the whole experimental period.
3. Tracheotomized rats (8–12 per dose and surfactant) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min⁻¹, inspiration expiration ratio of 1 : 2, peak inspiratory pressure of 28 cmH₂O at positive endexpiratory pressure (PEEP) of 8 cmH₂O. Animals were ventilated for one hour after the last lavage and thereafter the surfactants were intratracheally instilled. During the whole experimental period the ventilation was not changed.
4. Partial arterial oxygen pressures (PaO₂, mmHg) at 30 min and 120 min after treatment were used for statistical comparison. All protein containing surfactants caused a dose-dependent increase of the reduced PaO₂ values at 30 min after treatment. The protein-free surfactants showed only weak dose-dependent increase in PaO₂ values at this time. This difference between the protein-containing and the protein-free surfactants was even more pronounced when comparing the PaO₂ values at 120 min after treatment. Only rSP-C surfactant, bLES and Infasurf showed a dose-dependent increase in PaO₂ at this time.
5. With this animal model of late treatment it is possible even to differentiate between bovine derived surfactants. The differences between protein-containing and protein-free surfactants become even more pronounced. From the comparison of rSP-C surfactant with bovine-derived surfactants and the PL surfactant without rSP-C, it can be concluded that addition of rSP-C is sufficient to achieve the same activity as that of natural surfactants.

     

Effects of positive end-expiratory pressure on hyaline membrane formation in a rabbit model of the neonatal respiratory distress syndrome

Sixteen rabbits were anaesthetized and subjected to saline lavage of the lungs to produce surfactant deficiency. This resulted in an arterial oxygen tension of less than 12 kPa on 100% inspired oxygen and an inflection point on the pressure-volume curve at a pressure of 8–12 mmHg. After lavage the animals were randomly assigned to receive either conventional mechanical ventilation (CMV) with a positive end-expiratory pressure (PEEP) of 1–2 mmHg (group I —low PEEP) or CMV with PEEP equal to the inflection point pressure (group II — high PEEP). Mean airway pressures were kept at 14–16 mmHg in both groups by increasing the inspiratory: expiratory time ratios in the low PEEP group. The 5-h protocol was completed by 4 animals in group I and 6 animals in group II, early death usually being associated with a metabolic acidosis. On 100% oxygen, the mean PaO₂ at 2-h post-lavage was 15.2±8.3 kPa in group I and 39.6±21.8 kPa in group II. Group I had much lower end-expiratory lung volumes (3.0±1.5 ml above FRC) than group II (34.9±12.2 ml above FRC). Histological examination of the lungs revealed significantly less hyaline membrane formation in group II (p=0.001). Thus, the prevention of alveolar collapse by the use of high PEEP levels appears to reduce lung damage in this preparation.     

Effect of the glucocorticosteroid budesonide and a novel phosphodiesterase type 4 inhibitor CDP840 on antigen-induced airway responses in neonatally immunised rabbits.

1. The effects of the inhaled corticosteroid budesonide and a novel PDE 4 inhibitor CDP840 given systematically, were evaluated in a model of antigen-induced airway inflammation in the rabbit. 2. Adult litter-matched NZW rabbits (2.4-3.5 kg) immunised within 24 h of birth with Alternaria tenuis antigen were pretreated with budesonide (total dose 100 micrograms, inhaled over 2 days) or CDP840 (total dose 7 mg kg-1, i.p. over 3 days), before antigen challenge. For each drug-treated group a parallel group of rabbits was pretreated with the appropriate vehicle. In all groups airway responsiveness to inhaled histamine was assessed and bronchoalveolar lavage (BAL) performed 24 h before and after antigen challenge. 3. Basal lung function in terms of total lung resistance (RL; cmH2O l 1s-1) and dynamic compliance (Cdyn; ml cmH2O-1) were unaltered by pretreatment with budesonide or CDP840 compared to their respective vehicles 24 h before or after antigen challenge. 4. The RL component of the acute bronchoconstriction induced by inhaled Alternaria tenuis aerosol was unaffected by pretreatment with budesonide. However, budesonide prevented the fall in Cdyn due to antigen. Treatment with CDP840 significantly reduced antigen-induced acute bronchoconstriction in terms of both RL and Cdyn. 5. Airway hyperresponsiveness (AHR) to inhaled histamine was indicated by reduced RL PC50 (2.4-4.5 fold) and Cdyn PC35 (2.1-3.9 fold) values 24 h after antigen challenge. Treatment with either budesonide or CDP840 abolished the antigen-induced increase in responsiveness to inhaled histamine. 6. Total cells recovered per ml of BAL fluid increased 24 h after antigen challenge. Antigen-induced pulmonary eosinophilia was reduced (93%) in budesonide and (85%) in CDP840 treated rabbits. Antigen-induced increases in neutrophil numbers were reduced (76%) with budesonide but not CDP840 pretreatment. 7. Inhalation of Alternaria tenuis aerosol elicited an acute bronchoconstriction, followed 24 hours later by an increased responsiveness to inhaled histamine and pulmonary neutrophil and eosinophil recruitment. CDP840 was more effective than budesonide in preventing the antigen-induced increase in total lung resistance (RL); however, both drugs prevented the antigen-induced reduction in dynamic compliance (Cdyn). CDP840 and budesonide also prevented antigen-induced AHR and eosinophilia in the immunised rabbit.     

双肺同期大容量肺泡灌洗56例分析

目的总结全麻下双肺大容量肺泡灌洗术的经验。方法回顾性分析2006年4月～2008年12月对56例患者行全麻下双肺同期大容量肺泡灌洗的病例资料。结果56例患者第一侧肺灌洗残留液量241.5±192.1ml,最多残留620ml,6例完全回收。第二侧肺灌洗残留液量362.3±186.4ml,最多残留790ml,5例完全回收。第一侧肺灌洗后气道压增加10.2±5.4cmH2O。两侧肺灌洗间隔时间68.2±15.8min。结论双肺同期大容量肺泡灌洗法节约医疗资源,副作用少安全性高,可减轻患者痛苦和降低医疗费用。     

盐酸戊乙奎醚注射液对呼吸功能不全患者呼吸力学的影响

目的拟对应用盐酸戊乙奎醚注射液前后呼吸力学参数的变化进行比较,旨在探讨盐酸戊乙奎醚注射液用于治疗呼吸系统有关疾病潜在的可能性。方法选择呼吸功能不全气管插管呼吸机支持通气ICU患者20例,全部患者均静注咪达唑仑5 mg,静注维库溴铵0.1 mg/kg维持肌松,呼吸机设定为定容模式,设定潮气量7 mL/kg,I∶E为1∶2,频率14次/min。采动脉血做血气分析,同时记录下列数值:呼气一秒率(V1.0)、肺胸顺应性(CT)、气道峰压(Ppeak)和气道平均压(Pmean)。然后静脉推注盐酸戊乙奎醚注射液1 mg,给药后每5 min记录1次上述呼吸力学指标至35 min,并于给药后35 min再次采动脉血行血气分析。结果给药前V1.0为83.17%±3.99%,给药后逐渐上升,至20 min和25 min时分别达91.08%±4.48%和90.83%±4.47%(P<0.05)。CT给药前为(32.67±5.23)mL/cmH2O,给药后逐渐上升,至15 min和20 min时分别达(36.92±5.95)mL/cmH2O和(37.67±6.18)mL/cmH2O(P<0.05)。Ppeak给药前为(16.08±3.60)cmH2O,至给药后15 min下降至(13.82±2.79)cmH2O,此后一直维持在这一水平。Pmean给药前为(15.83±3.43)cmH2O,至给药后15 min下降至(13.04±2.69)cmH2O,此后一直维持在这一水平。结论盐酸戊乙奎醚注射液能够改善已有肺疾患病人的呼吸力学指标。     

A combined in vivo/in vitro small animal model for studying pulmonary responses

A model has been developed which allows an isolated lung to be perfused by a blood-PSS solution continuously processed by an intact animal. This model combines the advantage of control of the isolated perfused lung with a recirculated perfusate that is physiologically maintained. Substances that are generated by the isolated lung are, therefore, removed by metabolism in the intact animal and essential consumables in the perfusate are restored. Studies were performed in rabbits utilizing isolated perfused lung both with and without the intact animal processing the perfusate. The greatest pressor responses to hypoxic ventilation are obtained with a non-processed recirculated perfusate circuit, but the pressor responses decrease with time (12.5 +/- 1.7 cmH2O to 8.2 +/- 1.3 cmH3O) and the baseline pressure is higher initially (18.5 +/- 0.7 mmH2O). With the whole animal in the circuit, the baseline pressure and the initial hypoxic pressor responses are not as large, but are maintained constant (6.8 +/- 0.5 cmH2O to 8.1 +/- 1.0 cmH2O) over the same time period. When the isolated lungs are perfused with either blood-PSS or PSS in a non-processed, non-recirculated system, the hypoxic responses are 8.7 +/- 1.7 cmH2O and 5.7 +/- 1.0 cmH2O at the beginning of the study and decrease with time to 6.5 +/- 1.3 cmH2O and 4.2 +/- 1.0 cmH2O, respectively. The response of the isolated lung is, therefore, more stable with time and shows less individual variability when the whole animal perfusion circuit is employed.