Inactivation of exogenous surfactant in experimental respiratory failure induced by hyperoxia

Adult guinea pigs were exposed to 100% oxygen until, after 54-85 h, they developed severe respiratory insufficiency. One subgroup of animals was ventilated artificially with 100% oxygen for an additional 60-960 min. When the PaO2 was less than 15 kPa or the PaCO2 greater than 20 kPa, 1 ml of porcine surfactant (phospholipid concentration 80 mg.ml-1) was instilled via the trachea. These animals were ventilated for one more hour and then sacrificed. Surfactant instillation did not improve the blood gases, nor the pulmonary pressure-volume characteristics. All hyperoxia-exposed guinea pigs showed prominent histologic lung lesions, including intraalveolar edema and desquamation of airway epithelium. Compared to normal guinea pigs the volume density of intraalveolar "gas" was decreased and that of intraalveolar fluid increased. The alveolar expansion pattern in histologic sections was not improved in the surfactant-treated animals, compared to hyperoxia-exposed guinea pigs studied immediately after death. In hyperoxia-exposed animals, about 1.5 ml of edema fluid was sampled from the airways. Evaluated with pulsating bubble, our surfactant preparation had a minimum surface tension (gamma min) close to zero. However, the gamma min values of edema fluid from surfactant-treated and nontreated guinea pigs were both about 20 mN.m-1. the edema fluid thus seemed to inhibit the essential physical properties of exogenous surfactant. This, together with the prominent lung lesions, may explain the failure of surfactant replacement therapy at a late stage of hyperoxia-induced respiratory failure.     

Surfactant inactivation and surfactant replacement in experimental models of ARDS

Lung structure and function, and the effect of surfactant replacement, were studied in three animal models of adult respiratory distress syndrome (ARDS): surfactant depletion by repeated lung lavage, proteinaceous pulmonary edema induced by prolonged exposure to hyperoxia, and inoculation with hybridoma making an antibody to the hydrophobic surfactant-associated protein, SP-B. Surfactant replacement therapy restored normal gas exchange in respiratory failure induced by repeated lung lavage but was ineffective in animals with severe lung parenchymal lesions induced by hyperoxia or antibody to SP-B. Lung edema fluid from animals exposed to hyperoxia inhibited surfactant function in a concentration-dependent manner. These observations indicate that, in experimental ARDS, the effect of surfactant replacement depends on the type of animal model and, especially, on the degree of lung injury present at the time of therapy.     

High surface tension pulmonary edema

Dogs were anesthetized with pentobarbital and placed on a piston ventilator with room air. Ten animals received an endobronchial lavage of normal saline (3 mg/kg). Ten other animals received an endobronchial lavage of the same volume of a nonionic detergent, Tween 20, 5% in saline. Detergent lavage was shown by Wilhelmy balance to increase surface tension of lung extracts. Saline lavage did not alter the surface tension of lung extracts. No significant differences between the groups were noted in cardiac output, left ventricular and diastolic pressure, mean pulmonary artery pressure, or colloid oncotic pressure. Static compliance and arterial PO2 were decreased following detergent lavage. Animals were sacrificed 2 hr after lavage and pulmonary extravascular water volume (PEWV) was measured gravimetrically. Saline-lavaged lungs with normal surface tension had a PEWV of 4.3 ml/g dry lung. Tween-lavaged lungs with increased surface tension had a PEWV of 5.3 ml/g dry lung (P less than 0.005). When the estimated volume of residual lavage solution remaining in the lung parenchyma was subtracted from the total wet lung wt, the corrected PEWV was 3.62 +/- 0.12 ml/g dry lung for saline-lavaged lung and 4.76 +/- 0.19 ml/g dry lung for Tween-lavaged lung. PEWV for 11 control animals ventilated 2 hr without lavage was 3.61 +/- 0.13 ml/g dry lung. It is concluded that, experimentally, high alveolar surface tension can induce pulmonary edema even when pulmonary microvascular hydrostatic and colloid oncotic pressures are normal.     

测定胎盘型碱性磷酸酶判定烟雾吸入所致肺泡I型细胞损害

通过动态观察血浆及支气管肺泡灌洗液(BALF)中PLAP的变化,探讨烟雾吸入所致肺泡Ⅰ型细胞损害及其与肺损伤发生发展的关系,采用大鼠烟雾吸入伤模型,分别检测了正常对照及致伤2,6,12和24小时动物的动脉血气、肺水量、BALF中总蛋白和白蛋白含量,BALF和血浆中PLAP含量,并作了病理检查。结果表明:动物伤后出现急性呼吸衰竭和严重肺水肿,BALF中总蛋白及白蛋白含量明显升高;血浆及BALF中PLAP水平亦显著增加,且与BALF中蛋白含量的改变相关显著;病理检查亦见严重肺泡Ⅰ型细胞损害。提示PLAP不仅可作为肺泡Ⅰ型细胞损害的标志,而且与烟雾吸入伤后肺泡一毛细血管膜通透性增加有密切关系。     

The use of positive end-expiratory pressure in the management of the acute respiratory distress syndrome

Clinical and experimental research on the effects of positive end-expiratory pressure (PEEP) has produced a plethora of information during the last two decades. The application of PEEP is expected to increase PaO2; however, it is generally agreed that simply using increased PaO2 as the end point is inappropriate. Four mechanisms have been proposed to explain the improved pulmonary function and gas exchange with PEEP: 1) increased functional residual capacity; 2) alveolar recruitment; 3) redistribution of extravascular lung water; and 4) improved ventilation-perfusion matching. The optimal method of applying PEEP is still controversial. The main effect of augmenting PEEP is maintain recruitment of alveolar units that were previously collapsed. Thus, since tidal volume is distributed to more alveoli, peak airway pressure is reduced and compliance is increased. During acute lung injury, and depending on the severity of lung disease, PEEP can markedly alter the compliance of the lung by alveolar recruitment. The greater the alveolar collapse and pulmonary edema, the more the compliance curve of the respiratory system shifts downward and to the right. As PEEP is applied and alveoli recruited, the pressure-volume curve shifts upward and to the left. Despite its intuitive benefit, there were very few controlled studies of the effects of PEEP on ARDS outcome and no prospective randomised controlled trial of PEEP has been ever carried out in patients with acute lung injury and/ or ARDS to evaluate its efficacy until recently.     

Reversible pulmonary oxygen toxicity in the primate.

In order to investigate the effects of high concentrations of oxygen on the lung, experiments were performed on 18 baboons exposed to a humidified environment of 95% oxygen for five days. Open lung biopsies for biochemical assay, histologic and electron microscopic analysis and measurement of tissue respiration were performed before and after oxygen exposure. Pulmonary function was evaluated by measurement of arterial blood gases, compliance, closing capacity (CC), functional residual capacity (FRC), total lung capacity (TLC), residual volume (RV) and vital capacity (VC) before and after exposure and then at seven and 14 days in the animals which recovered. Six baboons removed from the oxygen environment after 96--110 hours and exposed to room air died within three to 20 hours of profound hypoxemia (PaO2 40 +/- 6). The remaining 12 baboons were successfully weaned to room air over a three day period with a return of ABGs to control values (PaO2 89+/- 2). Electron microscopic analysis of alveolar membranes exposed to 120 hours of hyperoxia demonstrated endothelial cell swelling, interstitial alveolar membrane edema, and an increased predominance of Type II pneumocytes. Lung volume measurements showed significant decreases in TLC (25%), VC (34%), CC/TLC (28%) and dynamic compliance (47%). Biochemical studies indicated a shift toward anaerobic metabolism with a decrese in tissue oxygen consumption, reduced cytochrome oxidase activity, and increased lung lactic acid production. These changes were all found to be reversible in the 12 baboons slowly weaned back to room air.     

Cardiopulmonary effects of oleic acid-induced pulmonary edema and mechanical ventilation

In order to define the mechanisms whereby cardiac output and arterial oxygen transport are reduced by acute permeability pulmonary edema and by positive end-expiratory pressure (PEEP), hemodynamic, respiratory, and lung water changes were measured in 12 mechanically ventilated dogs prior to the injection of oleic acid and at 1, 2.5, and 4 hr after the injection. Measurements were performed at each interval before and after the addition of 20 cm H2O PEEP. Positive end-expiratory pressure was not continued between measurements. One hour after the oleic acid injection, the lung water content and the pulmonary vascular resistance had increased more than 100% while the right ventricular (RV) volume, RV stroke volume, and PaO2 had decreased more than 35%. Each application of PEEP increased the PaO2 to control levels. However, PEEP also significantly increased the lung water content and pulmonary vascular resistance, and decreased the RV volume and stroke volume by 33%. The extravasation of fluid from the intravascular to the interstitial and alveolar spaces of the lung with oleic acid pulmonary edema is associated with substantial decreases in right ventricular volume and stroke volume and significant increases in the pulmonary vascular resistance. Treatment with 20 cm H2O PEEP further increases the lung water content and pulmonary vascular resistance and substantially reduces the right ventricular volume and stroke volume.     

Morphology and pathogenesis of desquamative interstitial pneumonitis.

Thirty human lung biopsy specimens have been diagnoses as desquamative interstitial pneumonitis. Six cases had intraalveolar lesions, believed to be early, while 20 had advanced disease characterised by intraalveolar cellular clumps, alveolar wall fibrosis, distortion, and loss of pulmonary parenchyma. Electron microscopy, high resolution light microscopy, and cytological examination have shown that the characteristic clumps in the alveolar air spaces are formed predominantly by enlarged and aggregated macrophages. Lymphocytes and eosinophils are also present in the intraalveolar clumps and in alveolar walls. Inflammation and immunological mechanisms are suggested as causes of the cellular clumping. Interstitial pneumonitis, alveolar wall fibrosis, changes in the alveolar epithelium, and loss of lung parenchyma are believed to be secondary events.     

肺灌洗及外源性肺表面活性物质治疗烟雾吸入性损伤的实验研究

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

Experimental study of dynamic changes in elastase-antiprotease in rabbits in the early stage of inhalation injury

In this experiment, rabbit model with smoke inhalation injury was used. The study was designed to observe the dynamic changes of elastase activities of polymorphonuclear leukocytes (PMN), alveolar macrophages (AM) and bronchoalveolar lavage fluid (BALF); and trypsin inhibitory capacities of serum and BALF (STIC & BTIC). The relationships between these changes and acute lung injury, as well as the concomitant changes of arterial blood gas levels, lung water volume and pathomorphology of trachea and lung tissues were also observed. It was found that after injury the elastase activities of PMN and AM were markedly reduced, and the elastase activity of BALF was rapidly increased. STIC was also reduced. PaO2 progressively dropped and PaCO2 progressively increased. Animals showed respiratory distress. Pathomorphological phagocytes aggregations in lungs, pulmonary edema and pneumorrhagia were found. There were serious destructions of capillary endothelial cells, alveolar epithelial cells, basement membranes and interstitial fibers. The number of elastic fibers of parenchyma decreased. The lung water volume was markedly increased, and there was a significant correlation between the increment of extravascular lung water and the rising of elastase activity of BALF. On the basis of our observation, it is proposed that the imbalance of elastase-antiprotease may play an important role in the development of acute lung injury after smoke inhalation.     

Liquid ventilation improves pulmonary function, gas exchange, and lung injury in a model of respiratory failure.

OBJECTIVE: The authors evaluated gas exchange, pulmonary function, and lung histology during perfluorocarbon liquid ventilation (LV) when compared with gas ventilation (GV) in the setting of severe respiratory failure. BACKGROUND: The efficacy of LV in the setting of respiratory failure has been evaluated in premature animals with surfactant deficiency. However, very little work has been performed in evaluating the efficacy of LV in older animal models of the adult respiratory distress syndrome (ARDS). METHODS: A stable model of lung injury was induced in 12 young sheep weighing 16.4 +/- 3.0 kg using right atrial injection of 0.07 mL/kg of oleic acid followed by saline pulmonary lavage and bijugular venovenous extracorporeal life support (ECLS). For the first 30 minutes on ECLS, all animals were ventilated with gas. Animals were then ventilated with either 15 mL/kg gas (GV, n = 6) or perflubron ([PFC], LV, n = 6) over the ensuing 2.5 hours. Subsequently, ECLS was discontinued in five of the GV animals and five of the LV animals, and GV or LV continued for 1 hour or until death. MAIN FINDINGS: Physiologic shunt (Qps/Qt) was significantly reduced in the LV animals when compared with the GV animals (LV = 31 +/- 10%; GV = 93 +/- 4%; p < 0.001) after 3 hours of ECLS. At the same time point, pulmonary compliance (CT) was significantly increased in the LV group when compared with the GV group (LV = 1.04 +/- 0.19 mL/cm H2O/kg; GV = 0.41 +/- 0.02 mL/cm H2O/kg; p < 0.001). In addition, the ECLS flow rate required to maintain the PaO2 in the 50- to 80-mm Hg range was substantially and significantly lower in the LV group when compared with that of the GV group (LV = 14 +/- 5 mL/kg/min; GV = 87 +/- 15 mL/kg/min; p < 0.001). All of the GV animals died after discontinuation of ECLS, whereas all the LV animals demonstrated effective gas exchange without extracorporeal support for 1 hour (p < 0.01). Lung biopsy light microscopy demonstrated a marked reduction in alveolar hemorrhage, lung fluid accumulation, and inflammatory infiltration in the LV group when compared with the GV animals. CONCLUSION: In a model of severe respiratory failure, LV improves pulmonary gas exchange and compliance with an associated reduction in alveolar hemorrhage, edema, and inflammatory infiltrate.     

Bronchoscopic surfactant administration preserves gas exchange and pulmonary compliance after single lung transplantation in dogs

BACKGROUND: Surfactant abnormalities have been implicated in reperfusion injury and respiratory failure in lung transplantation. METHODS: We investigated the efficacy of bronchoscopic administration of a bovine natural lung surfactant extract (Alveofact) to improve gas exchange and lung mechanics after heterologous left lung transplantation in foxhounds (+4 degrees C ischemia for 24 hours, conservation with Euro-Collins solution). Animals received either no surfactant therapy (untreated controls, n = 6) or 50 mg/kg body weight (prior to explantation, only graft) and 200 mg/kg body weight Alveofact (immediately after reperfusion, both lungs, n = 6). After lung transplantation, separate but synchronized ventilation of each lung was performed in a volume-controlled, pressure-limited mode for 12 hours, with the animals prone. Small catheters were inserted into the pulmonary veins of both the graft and the recipient's native lung for separate blood gas analysis. In the control group, marked protein leakage, influx of neutrophils into the alveolar space, and pulmonary edema formation (extravascular lung water; wet/dry ratio) were encountered in the transplanted lung but only to a very minor extent in the recipient's native lung. RESULTS: Lung compliance values and arterial oxygenation progressively deteriorated in the transplanted but not in the native lungs. Pulmonary hemodynamics did not change significantly. Surfactant administration did not significantly influence the development of reperfusion edema, protein leakage, and neutrophil influx into the grafts. However, surfactant restored the surface activity and the gas exchange (PaO2/FIO2 of 201.2 +/- 20.2 mm Hg vs 119.8 +/- 21.7 mm Hg in controls; P <.05) in the transplanted lungs, and compliance was markedly improved in the surfactant-treated animals (18.8 +/- 1.8 mL/mbar vs 11.5 +/- 1.6 mL/mbar in the controls; P <.05). CONCLUSION: Bronchoscopic surfactant administration does not prevent leukocyte influx or vascular leakage but does protect against respiratory failure and improves lung mechanics in single lung transplantation in dogs.     

Protective Effects of Isoflurane Pretreatment in Endotoxin-induced Lung Injury

Background: The concept of antiinflammatory effects of volatile anesthetics is well established in vitro and in some organ systems. Their protective role in lung injury, however, remains to be elucidated. The authors hypothesized that in the lung, isoflurane pretreatment may attenuate neutrophil infiltration and reduce endotoxin-induced injury.

Methods: Male C57Bl/6 mice were exposed to aerosolized lipopolysaccharide. Neutrophil recruitment into the pulmonary vasculature and migration into the different lung compartments (interstitium and alveolar air space) were determined by flow cytometry. Capillary protein leakage, formation of lung edema, and concentration of the chemokines keratinocyte-derived chemokine (CXCL1) and macrophage inflammatory protein 2 (CXCL2/3) in bronchoalveolar lavage were compared in mice with or without isoflurane treatment (1.4% inspired for 30 min) at different times before and after endotoxin exposure.

Results: Endotoxin inhalation induced significant neutrophil migration into all lung compartments. Isoflurane pretreatment attenuated both neutrophil recruitment into lung interstitium and alveolar space when given 1 or 12 h before or 1 h after lipopolysaccharide but not at 4, 6, or 24 h before endotoxin exposure. Isoflurane pretreatment 1 or 12 h before lipopolysaccharide also reduced protein leakage and pulmonary edema. Production of CXCL1 and CXCL2/3 in the bronchoalveolar lavage was reduced when isoflurane was given 1 h but not 12 h before lipopolysaccharide, suggesting different mechanisms for early and late protection.     

Improvement of rat lung structure and function after preservation with celsior

Ischemia/reperfusion-induced increase in pulmonary microvascular permeability was shown to be reduced after preservation with Celsior. We investigated reimplantation-induced lung injury in isolated, reperfused rat lungs after preservation via the pulmonary artery with Celsior, Celsior + prostacyclin, and reduced-potassium (40 mmol) Euro-Collins solution (40 ml/kg/body wt each) followed by 2 h of cold ischemia. Arterial and veneous oxygen tensions were recorded during 50 min of in vitro reperfusion after which the lungs (10 right lungs per experimental group) were fixed by vascular perfusion. The tissue was further processed for microscopy, and histological changes were quantified stereologically. Lung preservation with Celsior resulted in a significantly higher volume of air-filled alveolar space with a large proportion of widely distended alveoli compared with the other groups. In the Euro-Collins group the fraction of atelectatic alveoli exceeded that observed in Celsior-preserved lungs. In accordance, the difference between arterial and venous oxygen tensions was significant among Euro-Collins- and Celsior-protected lungs, with improved oxygenation values in the Celsior group. In contrast, addition of prostacyclin to Celsior treatment resulted in rather variable structural as well as functional data. There were no differences in the volumes of intraalveolar edema among the groups tested. However, the volume of alveolar tissue was increased in the Euro-Collins group. In conclusion, compared with Euro-Collins and Celsior + prostacyclin solutions, preservation with Celsior resulted in improved structural characteristics which in combination with improved oxygenation parameters supports the prospective advantage of Celsior in clinical organ preservation.     

Innovative pulmonary preservation of non-heart-beating donor grafts in experimental lung transplantation.

OBJECTIVE: Lung transplantation is limited by scarcity of donor organs. Lung retrieval from non-heart-beating donors (NHBD) might have the potential to extend the donor pool and has been reported recently. However, no studies in NHBD exist using the novel approach of retrograde preservation with Perfadex solution. METHODS: Asystolic heparinized pigs (n = 5/group) were continuously ventilated for 90, 180 or 300 min of warm ischemia. Lungs were then retrogradely preserved with Perfadex and stored at 4 degrees C in inflation. After 3 h of additional cold ischemia, left lung transplantation was performed. Hemodynamics, pO(2)/F(i)O(2) and dynamic compliance were monitored for 5 h. Intrapulmonary lung water was determined by both global wet-to-dry lung weight ratio (W/D ratio) and standard stereological examination of relative volume fractions of intraalveolar edema. All results were compared to sham-operated controls and to lungs obtained from standard heart-beating donors after retrograde preservation with Perfadex and 27 h of cold ischemia. Statistics comprised ANOVA analysis with repeated measures and Mann-Whitney tests. RESULTS: No mortality was observed. During flush preservation of NHBD lungs, continuous elimination of blood clots via the pulmonary artery was observed. Oxygenation, compliance, intraalveolar edema fraction and W/D ratio were comparable between groups, whereas PVR was significantly lower in sham-controls. CONCLUSIONS: Use of NHBD lungs is feasible and results in similar postischemic outcome when compared to sham-controls and standard preservation procedures even after 5 h of pre-harvest warm ischemia. Especially, the NHBD with high-risk constellations for intravascular coagulation might benefit from retrograde preservation by elimination of thrombi from the pulmonary circulation. This innovative technique might also be considered in situations, where brain-dead organ donors become hemodynamically unstable prior to onset of organ harvest. Further trials with longer warm and cold ischemic periods are initiated to further elucidate this promising approach of donor pool expansion.     

Lung retrieval from non-heart-beating donors: first experience with an innovative preservation strategy in a pig lung transplantation model

OBJECTIVE: Lung transplantation is limited by the scarcity of donor organs. Lung retrieval from non-heart-beating donors (NHBD) might extend the donor pool and has been reported recently. However, no studies in NHBD exist using the novel approach of retrograde preservation with Perfadex solution. METHODS: Heparinized asystolic pigs (n = 5, 30-35 kg) were ventilated for 90 min. The lungs were retrogradely preserved with Perfadex solution and stored inflated at 4 degrees C for 3 h. Left lung transplantation in the recipient was followed by exclusion of the right lung. Results were compared to sham-operated animals. Oxygenation, hemodynamics and dynamic compliance were monitored for 4 h. Infiltration of polymorphonuclear cells (PMNs) and stereological quantification of alveolar edema was performed. Statistical analysis comprised Kruskal-Wallis and Mann-Whitney tests and ANOVA analysis with repeated measures. RESULTS: No mortality was observed. During preservation, continuous elimination of blood clots via the pulmonary artery venting site was observed. Oxygenation and compliance were similar between groups, but sham controls showed significantly lower pulmonary vascular resistance. Stereological quantification revealed higher volume fractions of intra-alveolar edema in NHBD grafts, while PMN infiltration was comparable to sham controls. CONCLUSIONS: Use of NHBD lungs results in excellent outcome after 90 min of warm ischemia followed by retrograde preservation with Perfadex solution. This novel approach can optimize lung preservation by eliminating clots from the pulmonary circulation and might clinically be considered in brain-dead organ donors who become hemodynamically unstable prior to organ harvest. Further trials with longer warm and cold ischemic periods are necessary to further elucidate this promising approach to donor pool expansion.     

Protective effects of isoflurane pretreatment in endotoxin-induced lung injury

BACKGROUND: The concept of antiinflammatory effects of volatile anesthetics is well established in vitro and in some organ systems. Their protective role in lung injury, however, remains to be elucidated. The authors hypothesized that in the lung, isoflurane pretreatment may attenuate neutrophil infiltration and reduce endotoxin-induced injury. METHODS: Male C57Bl/6 mice were exposed to aerosolized lipopolysaccharide. Neutrophil recruitment into the pulmonary vasculature and migration into the different lung compartments (interstitium and alveolar air space) were determined by flow cytometry. Capillary protein leakage, formation of lung edema, and concentration of the chemokines keratinocyte-derived chemokine (CXCL1) and macrophage inflammatory protein 2 (CXCL2/3) in bronchoalveolar lavage were compared in mice with or without isoflurane treatment (1.4% inspired for 30 min) at different times before and after endotoxin exposure. RESULTS: Endotoxin inhalation induced significant neutrophil migration into all lung compartments. Isoflurane pretreatment attenuated both neutrophil recruitment into lung interstitium and alveolar space when given 1 or 12 h before or 1 h after lipopolysaccharide but not at 4, 6, or 24 h before endotoxin exposure. Isoflurane pretreatment 1 or 12 h before lipopolysaccharide also reduced protein leakage and pulmonary edema. Production of CXCL1 and CXCL2/3 in the bronchoalveolar lavage was reduced when isoflurane was given 1 h but not 12 h before lipopolysaccharide, suggesting different mechanisms for early and late protection. CONCLUSION: Isoflurane pretreatment reduces acute lung injury when given 1 or 12 h before an endotoxin challenge or within the first hour of an already established inflammation.     

Diffusing capacity limitations of the extent of lung volume reduction surgery in an animal model of emphysema

OBJECTIVE: The purpose of this study was to investigate in an elastase-induced emphysema rabbit model the effects of increasing resection volumes during lung volume reduction surgery on pulmonary compliance, forced expiratory air flow, and diffusing capacity to assess factors limiting optimal resection. METHODS: Emphysema was induced in 68 New Zealand White rabbits with 15,000 units of aerosolized elastase. Static respiratory system compliance, forced expiratory flow, and single-breath diffusing capacity were measured before the induction of emphysema, after the induction of emphysema, and 1 week after a bilateral upper and middle lobe lung volume reduction operation. RESULTS: Static respiratory system compliance with 60 mL insufflation above functional residual capacity increased with emphysema induction and then decreased progressively with resection of larger volumes of lung tissue (P =.001 by analysis of variance). Expiratory flow improved after lung resection in the rabbits with large resection volumes. In contrast, diffusing capacity tended to deteriorate with larger resection volumes (P =. 18). CONCLUSION: Improvements in respiratory system compliance and forced expiratory flow after lung volume reduction operations may account for the improvements seen clinically. Declines in diffusing capacity with extensive lung reduction may limit the clinical benefits associated with greater tissue resection volumes. Future investigations with animal models may reveal other physiologic parameters that may further guide optimal lung volume reduction procedures.     

Röntgenologische Lungenveränderungen bei polytraumatisierten Patienten während Dauerbeatmung

An analysis of roentgenographic pulmonary findings was done in 46 multiple trauma patients on controlled long term ventilation. 67% of the patients sustained thoracic trauma. The most common lung changes were interstitial and intraalveolar pulmonary edema and inflammatory pneumonia related to contusions, atelectasis and aspiration. The pulmonary lesions predominantly occurred in the middle and lower portions of each lung. The thoracic trauma group had four times as many lung changes than the non-thoracic trauma group. Daily roentgenographic controls are necessary in multiple trauma patients to explain a deterioration in pulmonary gas exchange leading to respiratory failure. To demonstrate discrete lesions in lung parenchyma, we recommend the high voltage technique for chest X-rays in intensive care units.     

The pathophysiology of smoke inhalation injury.

The consequences of near-lethal smoke inhalation in dogs were studied for a 72-hour period following injury. Progressive hypoxemia and decrease in compliance developed. Severe respiratory distress and frank pulmonary edema were not encountered. Respiratory insufficiecy was related more to alterations in ventilation perfusion ratios than to alveolar destruction. These data were related to clinical observations made by others. No deterioration of lung function was seen with crystalloid overload imposed upon smoke inhalation. The presence of bacterial infection in dogs surviving beyond 24 hours appears pathogenically significant.