5. New approaches to the management of flail chest.

Although continuous positive-pressure ventilation (internal pneumatic fixation) was a great advance in the treatment of flail chest and is now the standard treatment of this condition, early and late complications related to tracheostomy and long-term ventilation are associated with this method. These complications can be avoided by use of three recently adopted techniques--expectant therapy, intermittent mandatory ventilation with positive end-expiratory pressure, and early surgical stabilization of fractures. All patients should continue to be treated in intensive care units so that impending respiratory failure can be identified and treated. These newer forms of therapy not only have the advantages of avoiding complications inherent in tracheostomy and prolonged ventilation, but also decrease the length of hospital stay and expense of treatment.     

尿液分析及胸部X线筛查重度感染或者脓毒性休克感染源的回顾性分析

目的：评估重症监护室的重症感染或者脓毒性休克患者尿常规检查和胸部X线检查的准确性。方法：回顾性分析我院进入重症监护室的确诊为重症感染或者脓毒性休克的患者,收集所有入组患者的个人情况,进入监护室以后的尿液检查结果、胸部X线检查结果,以及体液细菌学培养的结果,分析上述数据与诊断泌尿系感染或者肺部感染之间关系。结果：我们回顾了400例患者,其中70例患者确诊为重症感染或者脓毒性休克,其中13例患者确诊为泌尿系感染（尿常规,白细胞〉10／高倍镜视野）,敏感性和特异性分别为81％（95％CI0．67-0．92）和65％（95％CI0．51—0．75）;36例患者确诊为肺部感染,胸部X线检查诊断肺部感染的的敏感性和特畀性分别为57％（95％C10．45—0．69）和92％（95％C10．82-0．93）。结论：对于脓毒血症或者脓毒性休克的患者,胸部X线检查敏感性较低,这可能与肺部X线检查干扰因素较多,并且肺部感染发生到出现影像学变化有一定的时间间隔：而尿液分析敏感性较高,但是也可能由于尿液中上皮细胞的存在而干扰诊断。     

Positive end-expiratory pressure and surfactant decrease lung injury during initiation of ventilation in fetal sheep

The initiation of ventilation in preterm, surfactant-deficient sheep without positive end-expiratory pressure (PEEP) causes airway injury and lung inflammation. We hypothesized that PEEP and surfactant treatment would decrease the lung injury from initiation of ventilation with high tidal volumes. Fetal sheep at 128-day gestational age were randomized to ventilation with: 1) no PEEP, no surfactant; 2) 8-cmH(2)O PEEP, no surfactant; 3) no PEEP + surfactant; 4) 8-cmH(2)O PEEP + surfactant; or 5) control (2-cmH(2)O continuous positive airway pressure) (n = 6-7/group). After maternal anesthesia and hysterotomy, the head and chest were exteriorized, and the fetus was intubated. While maintaining placental circulation, the fetus was ventilated for 15 min with a tidal volume escalating to 15 ml/kg using heated, humidified, 100% nitrogen. The fetus then was returned to the uterus, and tissue was collected after 30 min for evaluation of early markers of lung injury. Lambs receiving both surfactant and PEEP had increased dynamic compliance, increased static lung volumes, and decreased total protein and heat shock proteins 70 and 60 in bronchoalveolar lavage fluid compared with other groups. Ventilation, independent of PEEP or surfactant, increased mRNA expression of acute phase response genes and proinflammatory cytokine mRNA in the lung tissue compared with controls. PEEP decreased mRNA for cytokines (2-fold) compared with groups receiving no PEEP. Surfactant administration further decreased some cytokine mRNAs and changed the distribution of early growth response protein-1 expression. The use of PEEP during initiation of ventilation at birth decreased early mediators of lung injury. Surfactant administration changed the distribution of injury and had a moderate additive protective effect.     

Respiratory Nursing Interventions Following Tracheostomy in Acute Traumatic Cervical Spinal Cord Injury

Tracheostomy is frequently performed in severe cervical spinal cord injury (SCI) patients with the pulmonary dysfunction. A series of respiratory nursing interventions are required to plan tracheostomy removal. Tracheostomy was performed in 29 patients after acute traumatic cervical SCI. A series of respiratory nursing interventions were introduced in these patients after closed tracheostomy and decannulation, including closed tracheostomy tube training, manually assisted cough. Chacheostomy was successfully removed in 21 patients after the respiratory nursing interventions. In contrast, eight patients died from associated injuries. The average time from tracheostomy to decannulation was 40 days (14–104 days), the average time from closed tracheostomy to decannulation was 18.80 ± 13.50 days. Second tracheostomy was performed in one patient after 29 days’ removal due to pulmonary infection. One patient presented with delayed incision healing for 29 days. Closed tracheostomy tube training and manually assisted cough are key factors for tracheostomy removal, although intensive nursing are also needed. The time from tracheostomy to decannulation and from closed tracheostomy to decannulation is increased in case of "late" (>24 h) tracheostomy and longer mechanical ventilation.     

Injuries from antipersonnel mines: the experience of the International Committee of the Red Cross.

OBJECTIVE--To describe and quantify patterns of injury from antipersonnel mines in terms of distribution of injury, drain on surgical resources, and residual disability. DESIGN--Retrospective analysis. SETTING--Two hospitals for patients injured in war. SUBJECTS--757 patients with injuries from antipersonnel mines. MAIN OUTCOME MEASURES--Distribution and number of injuries; number of blood transfusions; number of operations; disability. RESULTS--Pattern 1 injury results from standing on a buried mine. These patients usually sustain traumatic amputation of the foot or leg; they use most surgical time and blood and invariably require surgical amputation of one or both lower limbs. Pattern 2 injury is a more random collection of penetrating injuries caused by multiple fragments from a mine triggered near the victim. The lower limb is injured but there is less chance of traumatic amputation or subsequent surgical amputation. Injuries to the head, neck, chest, or abdomen are common. Pattern 3 injury results from handling a mine: the victim sustains severe upper limb injuries with associated face injuries. Eye injuries are common in all groups. CONCLUSIONS--Patients who survive standing on a buried mine have greatest disability. Non-combatants are at risk from these weapons; in developing countries their social and economic prospects after recovery from amputation are poor.     

Survey of intensive care of severely head injured patients in the United Kingdom.

OBJECTIVES--To study practice in intensive care of patients with severe head injury in neurosurgical referral centres in United Kingdom. DESIGN--Structured telephone interview of senior nursing staff in intensive care unit of adult neurosurgical referral centre. SETTING--39 intensive care units in hospitals that accepted acute head injuries for specialist neurosurgical management, identified from Medical Directory and information from professional bodies. MAIN OUTCOME MEASURES--Details of organisation and administration of intensive care and patterns of monitoring and treatment for patients admitted with severe head injury. RESULTS--Patients were managed in specialist neurosurgical intensive care units in 21 of the centres and in general intensive care units in 18. Their intensive care was coordinated by an anaesthetist in 25 units and by a neurosurgeon in 12. Annual case-load varied between units: 20 received > 100 patients, 12 received 50-100, and seven received 25-49. Monitoring and treatment varied considerably between centres. Invasive arterial pressure monitoring was used routinely in 36 units, but central venous pressure monitoring was routinely used in 24 and intracranial pressure was routinely monitored in only 19. Corticosteroids were used to treat intracranial hypertension in 19 units. Seventeen units routinely aimed for arterial carbon dioxide pressure of 3.3-4.0 kPa, and one unit still used severe hyperventilation to a pressure of < 3.3 kPa. CONCLUSION--The intensive care of patients with acute head injuries varied widely between the centres surveyed. Rationalisation of the intensive care of severe head injury with the production of widely accepted guidelines ought to improve the quality of care.     

Sustained Inflation at Birth Did Not Alter Lung Injury from Mechanical Ventilation in Surfactant-Treated Fetal Lambs

Background

Sustained inflations (SI) are used with the initiation of ventilation at birth to rapidly recruit functional residual capacity and may decrease lung injury and the need for mechanical ventilation in preterm infants. However, a 20 second SI in surfactant-deficient preterm lambs caused an acute phase injury response without decreasing lung injury from subsequent mechanical ventilation.

Hypothesis

A 20 second SI at birth will decrease lung injury from mechanical ventilation in surfactant-treated preterm fetal lambs.

Methods

The head and chest of fetal sheep at 126±1 day GA were exteriorized, with tracheostomy and removal of fetal lung fluid prior to treatment with surfactant (300 mg in 15 ml saline). Fetal lambs were randomized to one of four 15 minute interventions: 1) PEEP 8 cmH₂O; 2) 20 sec SI at 40 cmH₂O, then PEEP 8 cmH₂O; 3) mechanical ventilation with 7 ml/kg tidal volume; or 4) 20 sec SI then mechanical ventilation at 7 ml/kg. Fetal lambs remained on placental support for the intervention and for 30 min after the intervention.

Results

SI recruited a mean volume of 6.8±0.8 mL/kg. SI did not alter respiratory physiology during mechanical ventilation. Heat shock protein (HSP) 70, HSP60, and total protein in lung fluid similarly increased in both ventilation groups. Modest pro-inflammatory cytokine and acute phase responses, with or without SI, were similar with ventilation. SI alone did not increase markers of injury.

Conclusion

In surfactant treated fetal lambs, a 20 sec SI did not alter ventilation physiology or markers of lung injury from mechanical ventilation.     

Inflammation and lung maturation from stretch injury in preterm fetal sheep

Mechanical ventilation is a risk factor for the development of bronchopulmonary dysplasia in premature infants. Fifteen minutes of high tidal volume (V(T)) ventilation induces inflammatory cytokine expression in small airways and lung parenchyma within 3 h. Our objective was to describe the temporal progression of cytokine and maturation responses to lung injury in fetal sheep exposed to a defined 15-min stretch injury. After maternal anesthesia and hysterotomy, 129-day gestation fetal lambs (n = 7-8/group) had the head and chest exteriorized. Each fetus was intubated, and airway fluid was gently removed. While placental support was maintained, the fetus received ventilation with an escalating V(T) to 15 ml/kg without positive end-expiratory pressure (PEEP) for 15 min using heated, humidified 100% nitrogen. The fetus was then returned to the uterus for 1, 6, or 24 h. Control lambs received a PEEP of 2 cmH(2)O for 15 min. Tissue samples from the lung and systemic organs were evaluated. Stretch injury increased the early response gene Egr-1 and increased expression of pro- and anti-inflammatory cytokines within 1 h. The injury induced granulocyte/macrophage colony-stimulating factor mRNA and matured monocytes to alveolar macrophages by 24 h. The mRNA for the surfactant proteins A, B, and C increased in the lungs by 24 h. The airway epithelium demonstrated dynamic changes in heat shock protein 70 (HSP70) over time. Serum cortisol levels did not increase, and induction of systemic inflammation was minimal. We conclude that a brief period of high V(T) ventilation causes a proinflammatory cascade, a maturation of lung monocytic cells, and an induction of surfactant protein mRNA.     

Penetrating chest wound: a case report.

An unusual penetrating chest injury was caused by a ball-point pen. Because of apparent penetration of the heart, preparations were made for an emergency open-heart procedure before emergency thoracotomy was undertaken, with the pen still in situ. The pen had bruised the epicardium but had not penetrated the pericardial sac. After removal of the pen, the wound was closed and a chest tube left in place. Recovery, apart from minor degrees of basal atelectasis, pleural effusion and wound infection, was uneventful. The outcome was consistent with that associated with current aggressive management of penetrating chest injuries. Management is based on three approaches. The primary one is intercostal thoracostomy tube drainage and fluid and blood replacement. In cases of massive hemorrhage or air leak, thoracotomy is necessary. The third approach is to prevent post-traumatic pulmonary insufficiency by using fine, high-efficiency filters during blood transfusion, avoiding excessive administration of intravenous fluids, performing tracheostomy after prolonged endotracheal intubation, and using a volume respirator with positive end-expiratory pressure. The average mortality for penetrating wounds of the heart is 25%.     

Reflex changes in tracheal smooth muscle tone during high-frequency oscillation

We examined the effect of high-frequency oscillatory ventilation (HFOV) on tracheal smooth muscle tension and upper airway resistance in anesthetized dogs. The animals were ventilated via a low tracheostomy by HFOV or conventional intermittent positive pressure ventilation (IPPV) with and without added positive end-expiratory pressure (PEEP). The transverse muscle tension of the trachea above the tracheostomy was measured and found to be lower during HFOV when compared with IPPV or IPPV with PEEP. When both vagi were cooled to 8 degrees C to interrupt afferent traffic from the lungs, there was no longer any difference between the modes of ventilation. In a second series of experiments, the airflow resistance of the upper airway above the tracheostomy was measured (Ruaw). During HFOV, Ruaw was significantly lower than during either IPPV or IPPV with PEEP. We conclude that HFOV induces a relaxation of tracheal smooth muscle and a reduction of upper airway resistance through a vagally mediated mechanism.     

Use of the kinetic treatment table to prevent the pulmonary complications of multiple trauma.

The kinetic treatment table (KTT) has been developed to prevent and treat complications of immobility. Because atelectasis and pneumonia may be related to immobility, we studied the effect of the KTT on the prevention and treatment of pulmonary complications in a prospective randomized study of 30 patients with severe traumatic injuries. All were receiving mechanical ventilation and were randomly assigned to treatment with a KTT or a conventional bed. Both groups received conventional medical-surgical therapy while pulmonary function, chest roentgenograms, and the presence or absence of lung infection were monitored for one week. In the patients who began the study with a clear chest roentgenogram, atelectasis and pneumonia were significantly less frequent in those treated with a KTT (P less than .05). Thus, the KTT can reduce pulmonary complications in selected patients with multiple trauma. The effect of this benefit on overall outcome is uncertain.     

损伤控制外科在严重胸外伤为主的全身多发伤救治中的应用

目的:探讨损伤控制外科(DCS)在严重胸外伤为主的全身多发伤救治中应用的临床效果。方法:2010年1月至2012年6月收治的57例患者采用早期全面治疗(ETC组),2012年7月至2013年12月收治的57例患者采用DCS理论救治(DCS组)。比较两组相关生理指标恢复情况及并发症的发生情况。结果:与ETC组比较,DCS组乳酸清除时间、体温恢复时间、PT和APTT恢复时间、住院时间、ICU治疗时间明显缩短,出血量明显减少(P0.05);DCS组腹腔感染、ARDS、应激性溃疡的发生率及死亡率均较ETC组明显降低(P0.05)。结论:严重胸外伤为主的全身多发伤救治中应用DCS理论可明显改善患者生理指标恢复,减少并发症,提高救治成功率。     

Retrospective Cohort Analysis of Chest Injury Characteristics and Concurrent Injuries in Patients Admitted to Hospital in the Wenchuan and Lushan Earthquakes in Sichuan,China

Background

The aim of this study was to compare retrospectively the characteristics of chest injuries and frequencies of other, concurrent injuries in patients after earthquakes of different seismic intensity.

Methods

We compared the cause, type, and body location of chest injuries as well as the frequencies of other, concurrent injuries in patients admitted to our hospital after the Wenchuan and Lushan earthquakes in Sichuan, China. We explored possible relationships between seismic intensity and the causes and types of injuries, and we assessed the ability of the Injury Severity Score, New Injury Severity Score, and Chest Injury Index to predict respiratory failure in chest injury patients.

Results

The incidence of chest injuries was 9.9% in the stronger Wenchuan earthquake and 22.2% in the less intensive Lushan earthquake. The most frequent cause of chest injuries in both earthquakes was being accidentally struck. Injuries due to falls were less prevalent in the stronger Wenchuan earthquake, while injuries due to burial were more prevalent. The distribution of types of chest injury did not vary significantly between the two earthquakes, with rib fractures and pulmonary contusions the most frequent types. Spinal and head injuries concurrent with chest injuries were more prevalent in the less violent Lushan earthquake. All three trauma scoring systems showed poor ability to predict respiratory failure in patients with earthquake-related chest injuries.

Conclusions

Previous studies may have underestimated the incidence of chest injury in violent earthquakes. The distributions of types of chest injury did not differ between these two earthquakes of different seismic intensity. Earthquake severity and interval between rescue and treatment may influence the prevalence and types of injuries that co-occur with the chest injury. Trauma evaluation scores on their own are inadequate predictors of respiratory failure in patients with earthquake-related chest injuries.     

Role of the Fas/FasL system in a model of RSV infection in mechanically ventilated mice

Infection with respiratory syncytial virus (RSV) in children can progress to respiratory distress and acute lung injury necessitating mechanical ventilation (MV). MV enhances apoptosis and inflammation in mice infected with pneumonia virus of mice (PVM), a mouse pneumovirus that has been used as a model for severe RSV infection in mice. We hypothesized that the Fas/Fas ligand (FasL) system, a dual proapoptotic/proinflammatory system involved in other forms of lung injury, is required for enhanced lung injury in mechanically ventilated mice infected with PVM. C57BL/6 mice and Fas-deficient ("lpr") mice were inoculated intratracheally with PVM. Seven or eight days after PVM inoculation, the mice were subjected to 4 h of MV (tidal volume 10 ml/kg, fraction of inspired O(2) = 0.21, and positive end-expiratory pressure = 3 cm H(2)O). Seven days after PVM inoculation, exposure to MV resulted in less severe injury in lpr mice than in C57BL/6 mice, as evidenced by decreased numbers of polymorphonuclear neutrophils in the bronchoalveolar lavage (BAL), and lower concentrations of the proinflammatory chemokines KC, macrophage inflammatory protein (MIP)-1α, and MIP-2 in the lungs. However, when PVM infection was allowed to progress one additional day, all of the lpr mice (7/7) died unexpectedly between 0.5 and 3.5 h after the onset of ventilation compared with three of the seven ventilated C57BL/6 mice. Parameters of lung injury were similar in nonventilated mice, as was the viral content in the lungs and other organs. Thus, the Fas/FasL system was partly required for the lung inflammatory response in ventilated mice infected with PVM, but attenuation of lung inflammation did not prevent subsequent mortality.     

Hydrogen inhalation reduced epithelial apoptosis in ventilator-induced lung injury via a mechanism involving nuclear factor-kappa B activation

We recently demonstrated the inhalation of hydrogen gas, a novel medical therapeutic gas, ameliorates ventilator-induced lung injury (VILI); however, the molecular mechanisms by which hydrogen ameliorates VILI remain unclear. Therefore, we investigated whether inhaled hydrogen gas modulates the nuclear factor-kappa B (NFκB) signaling pathway. VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg or 10 ml/kg without positive end-expiratory pressure). The ventilator delivered either 2% nitrogen or 2% hydrogen in balanced air. NFκB activation, as indicated by NFκB DNA binding, was detected by electrophoretic mobility shift assays and enzyme-linked immunosorbent assay. Hydrogen gas inhalation increased NFκB DNA binding after 1 h of ventilation and decreased NFκB DNA binding after 2 h of ventilation, as compared with controls. The early activation of NFκB during hydrogen treatment was correlated with elevated levels of the antiapoptotic protein Bcl-2 and decreased levels of Bax. Hydrogen inhalation increased oxygen tension, decreased lung edema, and decreased the expression of proinflammatory mediators. Chemical inhibition of early NFκB activation using SN50 reversed these protective effects. NFκB activation and an associated increase in the expression of Bcl-2 may contribute, in part, to the cytoprotective effects of hydrogen against apoptotic and inflammatory signaling pathway activation during VILI.     

Effect of lung-protective ventilation on severe Pseudomonas aeruginosa pneumonia and sepsis in rats

Pneumonia caused by Pseudomonas aeruginosa carries a high rate of morbidity and mortality. A lung-protective strategy using low tidal volume (V(T)) ventilation for acute lung injury improves patient outcomes. The goal of this study was to determine whether low V(T) ventilation has similar utility in severe P. aeruginosa infection. A cytotoxic P. aeruginosa strain, PA103, was instilled into the left lung of rats anesthetized with pentobarbital. The lung-protective effect of low V(T) (6 ml/kg) with or without high positive end-expiratory pressure (PEEP, 10 or 3 cmH(2)O) was then compared with high V(T) with low PEEP ventilation (V(T) 12 ml/kg, PEEP 3 cmH(2)O). Severe lung injury and septic shock was induced. Although ventilatory mode had little effect on the involved lung or septic physiology, injury to noninvolved regions was attenuated by low V(T) ventilation as indicated by the wet-to-dry weight ratio (W/D; 6.13 +/- 0.78 vs. 3.78 +/- 0.26, respectively) and confirmed by histopathological examinations. High PEEP did not yield a significant protective effect (W/D, 4.03 +/- 0.32) but, rather, caused overdistension of noninvolved lungs. Bronchoalveolar lavage revealed higher concentrations of TNF-alpha in the fluid of noninvolved lung undergoing high V(T) ventilation compared with those animals receiving low V(T). We conclude that low V(T) ventilation is protective in noninvolved regions and that the application of high PEEP attenuated the beneficial effects of low V(T) ventilation, at least short term. Furthermore, low V(T) ventilation cannot protect the involved lung, and high PEEP did not significantly alter lung injury over a short time course.     

AECOPD并重度呼吸衰竭患者有创机械通气的治疗时机探讨及其预后的影响因素分析

摘要 目的：探讨慢性阻塞性肺疾病急性加重（AECOPD）合并重度呼吸衰竭患者有创机械通气的治疗时机,并分析其预后的影响因素。方法：选取2020年3月~2021年12月期间于首都医科大学附属北京世纪坛医院治疗的161例AECOPD合并重度呼吸衰竭患者,按照气管插管时间分为早期组（n=89）和延期组（n=72）,对比两组治疗后临床指标、血气分析指标及28 d内病死率（预后）。根据预后的不同将患者分为死亡组（n=29）和存活组（n=132）,收集患者的一般资料和实验室资料,采用Logistic回归分析预后的影响因素。结果：早期组的总机械通气时间、有创通气时间、重症监护室（ICU）住院时间均短于延期组（P<0.05）。两组治疗后动脉血二氧化碳分压（PaCO₂）较治疗前下降,氧合指数（OI）、动脉血氧分压（PaO₂）较治疗前升高,且早期组变化程度大于延期组（P<0.05）。延期组28 d内病死率为15/72（20.83%）。早期组28 d内病死率为14/89（15.73%）,两组患者的28 d病死率对比无差异（P>0.05）。单因素分析结果显示,AECOPD合并重度呼吸衰竭患者的预后影响因素与并发呼吸机相关肺炎、并发多脏器功能不全综合征、年龄、PaCO₂、血红蛋白（Hb）、血尿素氮（BUN）、白细胞计数（WBC）、pH值、中性粒细胞计数/淋巴细胞计数比值（NLR）、血小板计数/淋巴细胞计数（PLR）、C反应蛋白（CRP）、D-二聚体（D-D）、B型尿钠肽有关（P<0.05）。AECOPD合并重度呼吸衰竭患者预后不良的危险因素主要有并发呼吸机相关肺炎、并发多脏器功能不全综合征、PaCO₂偏高、年龄偏大、Hb偏低、pH值偏低、D-D偏高（P<0.05）。结论：AECOPD合并重度呼吸衰竭患者早期使用有创机械通气,可有效改善血气分析,缩短有创通气时间、总机械通气时间、ICU住院时间。并发呼吸机相关肺炎、并发多脏器功能不全综合征、PaCO₂偏高、年龄偏大、Hb偏低、pH值偏低、D-D偏高均是导致AECOPD合并重度呼吸衰竭患者预后不良的危险因素。     

Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation (1-3, 5, 8, 26, 30, 33-36). ALI is defined by the acute onset of the disease, which leads to non-cardiac pulmonary edema and subsequent impairment of pulmonary gas exchange (36). We have developed a murine model of ALI by using a pressure-controlled ventilation to induce ventilator-induced lung injury (2). For this purpose, C57BL/6 mice are anesthetized and a tracheotomy is performed followed by induction of ALI via mechanical ventilation. Mice are ventilated in a pressure-controlled setting with an inspiratory peak pressure of 45 mbar over 1 - 3 hours. As outcome parameters, pulmonary edema (wet-to-dry ratio), bronchoalveolar fluid albumin content, bronchoalveolar fluid and pulmonary tissue myeloperoxidase content and pulmonary gas exchange are assessed (2). Using this technique we could show that it sufficiently induces acute lung inflammation and can distinguish between different treatment groups or genotypes (1-3, 5). Therefore this technique may be helpful for researchers who pursue molecular mechanisms involved in ALI using a genetic approach in mice with gene-targeted deletion.     

Effects of melatonin in an experimental model of ventilator-induced lung injury

Melatonin is a free radical scavenger and a broad-spectrum antioxidant and has well-documented immunomodulatory effects. We studied the effects of this hormone on lung damage, oxidative stress, and inflammation in a model of ventilator-induced lung injury (VILI), using 8- to 12-wk-old Swiss mice (n = 48). Animals were randomized into three experimental groups: control (not ventilated); low-pressure ventilation [peak inspiratory pressure 15 cmH(2)O, positive end-expiratory pressure (PEEP) 2 cmH(2)O], and high-pressure ventilation (peak inspiratory pressure 25 cmH(2)O, PEEP 0 cmH(2)O). Each group was divided into two subgroups: eight animals were treated with melatonin (10 mg/kg ip, 30 min before the onset of ventilation) and the remaining eight with vehicle. After 2 h of ventilation, lung injury was evaluated by gas exchange, wet-to-dry weight ratio, and histological analysis. Levels of malondialdehyde, glutathione peroxidase, interleukins IL-1beta, IL-6, TNF-alpha, and IL-10, and matrix metalloproteinases 2 and 9 in lung tissue were measured as indicators of oxidation status, pro-/anti-inflammatory cytokines, and matrix turnover, respectively. Ventilation with high pressures induced severe lung damage and release of TNF-alpha, IL-6, and matrix metalloproteinase-9. Treatment with melatonin improved oxygenation and decreased histological lung injury but significantly increased oxidative stress quantified by malondialdehyde levels. There were no differences in TNF-alpha, IL-1beta, IL-6, or matrix metalloproteinases caused by melatonin treatment, but IL-10 levels were significantly higher in treated animals. These results suggest that melatonin decreases VILI by increasing the anti-inflammatory response despite an unexpected increase in oxidative stress.     

Mechanisms of early pulmonary neutrophil sequestration in ventilator-induced lung injury in mice

Polymorphonuclear leukocytes (PMN) play an important role in ventilator-induced lung injury (VILI), but the mechanisms of pulmonary PMN recruitment, particularly early intravascular PMN sequestration during VILI, have not been elucidated. We investigated the physiological and molecular mechanisms of pulmonary PMN sequestration in an in vivo mouse model of VILI. Anesthetized C57/BL6 mice were ventilated for 1 h with high tidal volume (injurious ventilation), low tidal volume and high positive end-expiratory pressure (protective ventilation), or normal tidal volume (control ventilation). Pulmonary PMN sequestration analyzed by flow cytometry of lung cell suspensions was substantially enhanced in injurious ventilation compared with protective and control ventilation, preceding development of physiological signs of lung injury. Anesthetized, spontaneously breathing mice with continuous positive airway pressure demonstrated that raised alveolar pressure alone does not induce PMN entrapment. In vitro leukocyte deformability assay indicated stiffening of circulating leukocytes in injurious ventilation compared with control ventilation. PMN sequestration in injurious ventilation was markedly inhibited by administration of anti-L-selectin antibody, but not by anti-CD18 antibody. These results suggest that mechanical ventilatory stress initiates pulmonary PMN sequestration early in the course of VILI, and this phenomenon is associated with stretch-induced inflammatory events leading to PMN stiffening and mediated by L-selectin-dependent but CD18-independent mechanisms.