Pumpless extracorporeal interventional lung assist in patients with acute respiratory distress syndrome: a prospective pilot study

Introduction  

Pumpless interventional lung assist (iLA) is used in patients with acute respiratory distress syndrome (ARDS) aimed at improving extracorporeal gas exchange with a membrane integrated in a passive arteriovenous shunt. In previous studies, feasibility and safety of the iLA system was demonstrated, but no survival benefit was observed. In the present pilot study we tested the hypothesis that timely initiation of iLA using clear algorithms and an improved cannulation technique will positively influence complication rates and management of lung protective ventilation.     

肺部超声新评分法评估新生儿呼吸窘迫综合征机械通气撤机时机的应用价值

目的探讨肺部十四分区超声评分法评估新生儿呼吸窘迫综合征(NRDS)患儿机械通气撤机时机的临床应用价值。方法选取我院新生儿重症监护室使用机械通气治疗的NRDS患儿62例,根据撤机结果分为撤机成功组49例和撤机失败组13例,在达到临床撤机标准拟拔管前行床旁肺部超声检查,采用肺部六分区法、十分区法、十二分区法及十四分区法对两组患儿进行肺部超声评分(LUS),撤机失败者于再次插管前和再次撤机前再行LUS。绘制受试者工作特征(ROC)曲线分析不同分区方法LUS对撤机时机的预测价值。结果两组患儿四种肺部分区法获得的LUS比较,差异均有统计学意义(均P<0.05)。撤机失败组经肺部超声检查发现存在:4例明显肺水肿,5例后肺部大范围肺实变,2例肺底部大范围肺实变,1例右上肺大片肺不张,1例肺部超声未见异常但心脏超声发现心功能不全。ROC曲线分析显示,肺部十四分区法较其他三种分区方法对撤机时机有更好的诊断效能,以40.5分为截断值,其预测撤机失败风险的曲线下面积0.965,敏感性92.31%,特异性93.88%。结论肺部十四分区法对NRDS患儿机械通气撤机时机的评估具有良好的应用价值,可早期预测撤机失败高风险患儿,进一步指导临床诊疗,提高撤机成功率。     

Combination of high frequency oscillatory ventilation and interventional lung assist in severe acute respiratory distress syndrome

Background

The combination of high-frequency oscillatory ventilation (HFOV) and extracorporeal carbon dioxide removal with the interventional lung assist (iLA) in severe acute respiratory distress syndrome (ARDS) represents a novel treatment option.

Methods

The study used a retrospective single-center analysis of 21 consecutive adult patients with severe ARDS, ventilated with HFOV/iLA. Efficiency, side effects, and outcome of combined treatment are presented as median (interquartile range).

Measurements and Main Results

The following were used to determine patient characteristics: sequential organ failure assessment score, 14; simplified acute physiology score II, 41; and Murray score, 4. The duration of combined treatment was 6 days. The blood flow through the iLA was 1.9 L/min.The Pao₂/inspired fraction of oxygen ratio increased from 61 (47-86) to 98 (67-116) within 2 hours and to 106 (70-135) mm Hg at 24 hours. Paco₂ decreased from 58 (50-76) to 37 (29-47) mm Hg at 2 hours with normalization of pH 7.28 (7.16-7.36) to 7.43 (7.33-7.49) after 2 hours associated with hemodynamic stabilization. In 6 patients, complications due to iLA treatment were observed, and in 3 patients, complications associated with HFOV were seen. Weaning from HFOV/iLA was successful in 10 patients. The 30-day mortality rate was 43%, and hospital mortality rate was 57%.

Conclusion

The combination of HFOV/iLA is an option in severe pulmonary failure if conventional ventilation fails and pumpdriven extracorporeal membrane oxygenation therapy is not available.     

群体烧伤伤员空运后送的护理做法与体会

目的进一步研究群体烧伤病员远距离空运后送的护理组织与实施。方法对2006年34例烧伤伤员空运后送护理的全过程进行了回顾分析。结果34名伤员全部为男性,病重25人(占73.53%),病危3人(占8.82%),100%合并吸入性呼吸道损伤;重度吸入性损伤16人占47.06%,中度吸入性损伤18人占52.94%。空中飞行距离约1 600 km。按空运申请、空运前医疗护理准备、运送伤员到达登机点、组织伤员登机、实施空中医疗护理、组织伤员离机与交接、进行飞机的清洁与消毒、补充药材等8个阶段逐步展开救护。结论对于群体烧伤伤员空运后送,转运前的护理准备非常重要;对群体伤员进行分类编号管理,是防止护理工作混乱的基础。空中转送的医疗与护理具有独特性,但现代化的监护增加了转运的安全;统筹使用空中与地面的护理力量,可以提高护理组织绩效。     

Time course of physiologic variables in response to ventilator-induced lung injury

BACKGROUND: The time course of the physiological derangements that result from ventilator-induced lung injury has not been adequately described. Similarly, the regional topographies of pleural pressure and tissue edema have not been carefully mapped for this injury process. METHODS: Lung injury was induced in 9 normal pigs by ventilating for 6 hours at a transpulmonary pressure of 35 cm H(2)O, with the animals in the supine position. Eight additional normal pigs received right thoracotomy to place pleural-surface-pressure sensors prior to an identical period and intensity of injurious ventilation. Gas exchange and lung mechanics were tracked in all the animals. Cytokines (tumor necrosis factor alpha, interleukin 6, and interleukin 8) in peripheral blood were assayed at 2 hour intervals, beginning at the onset of mechanical ventilation, from all the animals. RESULTS: After a brief "induction" period, P(aO(2)) and tidal volume declined steadily in the animals that were ventilated to induce lung injury. The rate of decline was greater in the animals that received thoracotomy. The pleural pressure gradient steadily increased from ventral to dorsal. The serum cytokine levels did not evolve with developing injury, but cytokines were elevated at the onset of ventilation. Tissue edema, as assessed by the ratio of wet weight to dry weight, was greater in the thoracotomized animals than in the nonthoracotomized animals, and tissue edema tended to be greater in the caudal lung regions than in the cephalad lung regions. CONCLUSIONS: Following the induction period, the development of ventilator-induced lung injury progressed steadily and then plateaued, as assessed by quantitative physiology variables during 6 hours of ventilation at a transpulmonary pressure of 35 cm H(2)O. Greater injury developed in animals that had a coexisting potential insult (thoracotomy). Injury development was not paralleled by bloodborne inflammatory cytokines.     

A new pumpless extracorporeal interventional lung assist in critical hypoxemia/hypercapnia

OBJECTIVE: Pump-driven extracorporeal gas exchange systems have been advocated in patients suffering from severe acute respiratory distress syndrome who are at risk for life-threatening hypoxemia and/or hypercapnia. This requires extended technical and staff support. DESIGN: We report retrospectively our experience with a new pumpless extracorporeal interventional lung assist (iLA) establishing an arteriovenous shunt as the driving pressure. SETTING: University hospital. PATIENTS: Ninety patients with acute respiratory distress syndrome. INTERVENTIONS: Interventional lung assist was inserted in 90 patients with acute respiratory distress syndrome. MEASUREMENTS AND MAIN RESULTS: Oxygenation improvement, carbon dioxide elimination, hemodynamic variables, and the amount of vasopressor substitution were reported before, 2 hrs after, and 24 hrs after implementation of the system. Interventional lung assist led to an acute and moderate increase in arterial oxygenation (Pao2/Fio2 ratio 2 hrs after initiation of iLA [median and interquartile range], 82 mm Hg [64-103]) compared with pre-iLA (58 mm Hg [47-78], p < .05). Oxygenation continued to improve for 24 hrs after implementation (101 mm Hg [74-142], p < .05). Hypercapnia was promptly and markedly reversed by iLA within 2 hrs (Paco2, 36 mm Hg [30-44]) in comparison with before (60 mm Hg [48-80], p < .05], which allowed a less aggressive ventilation. For hemodynamic stability, all patients received continuous norepinephrine infusion. The incidence of complications was 24.4%, mostly due to ischemia in a lower limb. Thirty-seven of 90 patients survived, creating a lower mortality rate than expected from the Sequential Organ Failure Assessment score. CONCLUSIONS: Interventional lung assist might provide a sufficient rescue measure with easy handling properties and low cost in patients with severe acute respiratory distress syndrome and persistent hypoxia/hypercapnia.     

Role of poly-(ADP-ribose) synthetase in lipopolysaccharide-induced vascular failure and acute lung injury in pigs

PURPOSE: To assess the contribution of poly (adenosine 5'-diphosphate ribose) synthetase (PARS) to the development of bacterial lipopolysaccharide (LPS)-induced acute lung injury and vascular failure in pigs. MATERIALS AND METHODS: Four groups of anesthetized, paralyzed, and mechanically ventilated domestic white pigs. Group 1 served as control, whereas Escherichia coli LPS (20 microg/kg/h) was continuously infused in group 2. Group 3 received 20 mg/kg injection of 3-aminobenzamide (a selective inhibitor of PARS activity) 15 minutes before LPS infusion. Only 3-aminobenzamide and not LPS was injected in group 4. All animals were examined for 180 minutes. Systemic and pulmonary hemodynamics and lung mechanics were measured during the experimental period. Lung wet/dry ratio, bronchoalveolar lavage (BAL) protein levels and cell counts and lung nitrotyrosine (footprint of peroxynitrite) immunostaining were also measured in a few animals. RESULTS: LPS infusion evoked a progressive decline in systemic arterial pressure, a small increase in cardiac output, and biphasic elevation of pulmonary arterial pressure. Lung compliance declined progressively, whereas lung and total respiratory resistance rose significantly after LPS infusion. Prominent nitrotyrosine immunostaining was detected around small airways and pulmonary endothelium of LPS-infused animals. No significant changes in lung wet/dry ratio and BAL protein levels and cell counts were produced by LPS infusion. Pretreatment with 3-aminobenzamide did not alter the systemic and pulmonary hemodynamic responses to LPS infusion but eliminated the rise in pulmonary and total respiratory resistance. CONCLUSIONS: We concluded that PARS activation plays an important role in the changes of lung mechanics associated with LPS-induced acute lung injury but had no role in vascular failure.     

Electrical impedance tomography in monitoring experimental lung injury

Objective: To apply electrical impedance tomography (EIT) and the new evaluation approach (the functional EIT) in monitoring the development of artificial lung injury. Design: Acute experimental trial. Setting: Operating room for animal experimental studies at a university hospital. Subjects: Five pigs (41.3 ± 4.1 kg, mean body weight ± SD). Interventions: The animals were anaesthetised and mechanically ventilated. Sixteen electrodes were attached on the thoracic circumference and used for electrical current injection and surface voltage measurement. Oleic acid was applied sequentially (total dose 0.05 ml/kg body weight) into the left pulmonary artery to produce selective unilateral lung injury. Measurements and results: The presence of lung injury was documented by significant changes of PaCO₂ (40.1 mmHg vs control 37.1 mmHg), PaO₂ (112.3 mmHg vs 187.5 mmHg), pH (7.35 vs 7.42), mean pulmonary arterial pressure (29.2 mmHg vs 20.8 mmHg) and chest radiography. EIT detected 1) a regional decrease in mean impedance variation over the affected left lung (–41.4 % vs control) and an increase over the intact right lung ( + 20.4 % vs control) indicating reduced ventilation of the affected, and a compensatory augmented ventilation of the unaffected lung and 2) a pronounced fall in local baseline electrical impedance over the injured lung (–20.6 % vs control) with a moderate fall over the intact lung (–10.0 % vs control) indicating the development of lung oedema in the injured lung with a probable atelectasis formation in the contralateral one. Conclusion: The development of the local impairment of pulmonary ventilation and the formation of lung oedema could be followed by EIT in an experimental model of lung injury. This technique may become a useful tool for monitoring local pulmonary ventilation in intensive care patients suffering from pulmonary disorders associated with regionally reduced ventilation, fluid accumulation and/or cell membrane changes. Received: 22 December 1997 Accepted: 7 April 1998     

Trauma helicopter emergency medical services transport: Annotated review of selected outcomes-related literature

Based on its roots in military air evacuation, helicopter emergency medical services (HEMS) has always been emphasized as a tool for trauma transportation. Despite much discussion regarding resource allocation for HEMS, a literature search found little recent systematic review of pertinent studies. As HEMS utilization is subject to increased scrutiny in a health care dollar-conscious environment, it was felt that a compendium of available outcomes-related literature could assist those assessing utility of HEMS trauma transport. The current study utilized a Medline search to identify outcomes studies relative to HEMS trauma transport. The goal of this review is to provide a useful resource for those interested in pursuing systematic review of the HEMS trauma outcomes literature. The primary purpose of the review is bibliographic, but there is editorial comment after each paper's summary. The initial article in this two-part series focused on HEMS outcomes literature covering noninjured patients as well as papers assessing outcome in mixed trauma-nontrauma HEMS study groups. PREHOSPITAL EMERGENCY CARE 2002;6:359-371     

Inhaled budesonide in experimental chlorine gas lung injury: influence of time interval between injury and treatment

OBJECTIVE: To examine the time window between injury and treatment during which nebulized corticosteroid lessens lung injury induced by chlorine gas inhalation. DESIGN: An experimental laboratory study. SETTING: Academic research laboratory. SUBJECTS: Twenty-four juvenile female pigs. INTERVENTIONS: Twenty-four mechanically ventilated pigs were exposed to chlorine gas (400 PPM in air) for 20 min, then divided into four groups (six in each group). Nebulized budesonide (BUD) was given immediately (BUD 0 min), 30 min (BUD 30 min) or 60 min (BUD 60 min) after chlorine gas exposure. Six pigs receiving nebulized saline served as controls. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, gas exchange and lung mechanics were evaluated for 5 h after chlorine gas exposure. All animals had an immediate increase in airway and pulmonary artery pressure and a sharp drop of arterial oxygenation. The mean arterial oxygen tension of BUD 0 min and BUD 30 min animals was significantly higher than in the control and the BUD 60 min groups ( p<0.001). The recovery of lung compliance in the BUD 0 min and the BUD 30 min groups was significantly more rapid than in the control and the BUD 60 min groups ( p<0.001). The pulmonary wet to dry weight ratio was greater in the control group than in the BUD-treated groups ( p<0.05). CONCLUSION: Treatment with inhaled budesonide immediately or 30 min after chlorine gas lung injury had similar positive effects on symptoms and signs of pulmonary injury, whereas treatment delayed for 60 min was less effective.     

Early detection of acute lung injury uncoupled to hypoxemia in pigs using ultrasound lung comets

OBJECTIVE: Oleic acid-induced lung injury is an established experimental model of acute lung injury in pigs and is considered to reproduce the early exudative phase of acute respiratory distress syndrome. Ultrasound lung comets are an echographic sign of extravascular lung water, originating from thickened interlobular septa. The objective of this study was to evaluate the timing and relationship between the number of ultrasound lung comets, the Pao2/Fio2 ratio, and the static respiratory compliance in an experimental model of oleic acid-induced lung injury in pigs. DESIGN: Laboratory experiment. SETTING: Research institute. SUBJECTS: Ten anesthetized pigs. INTERVENTIONS: Acute lung injury was induced by injection of oleic acid (0.1 mL/kg, intravenously). Ultrasound lung comets, Pao2/Fio2, and static respiratory compliance were measured at baseline and at 15, 30, 60, and 90 mins after the injection of oleic acid. We evaluated ultrasound lung comets by transthoracic echography (7.5-MHz vascular probe), scanning on right and left hemithoraxes at 12 predefined scanning sites. MEASUREMENTS AND MAIN RESULTS: Acute lung injury/acute respiratory distress syndrome was present in all pigs at 90 mins. The number of ultrasound lung comets increased over time and was consistently earlier than the decrease in Pao2/Fio2. At 15 mins, ultrasound lung comets were markedly increased, but no significant changes in Pao2/Fio2 were observed. Accordingly, static respiratory compliance was dramatically reduced at 15 mins compared with baseline (17.04 +/- 1.82 vs. 34.84 +/- 2.62 mL/cm H2O, p < .05). CONCLUSIONS: Ultrasound lung comets, assessed by transthoracic echography, detected extravascular lung water accumulation very early in the course of the oleic acid lung injury in pigs, in the presence of a normal Pao2/Fio2. These results suggest that ultrasound lung comets could be a very early, noninvasive, and simple method to detect and quantify pulmonary edema in acute lung injury.     

Bilateral lavage with diluted surfactant improves lung function after unilateral lung contusion in pigs

OBJECTIVE: This study evaluates the effects of bronchoalveolar lavage with diluted surfactant on unilateral lung contusion-induced lung dysfunction. DESIGN: Randomized prospective animal study. SETTING: An animal laboratory. SUBJECTS: Twenty adult pigs, weighing 25-35 kg. INTERVENTIONS: Animals were randomly assigned to controls and surfactant treatment. Bilateral lavage with surfactant treatment began 30 mins after unilateral lung contusion. Then 25 mg/kg of body weight diluted Curosurf (5 mg/mL) was applied in a volume of 5 mL/kg of body weight. Observation time was 8 hrs postinjury. MEASUREMENTS AND MAIN RESULTS: The Pao2/Fio2 ratio fell from 500 to 250 and then recovered gradually in controls and surfactant-treated pigs. After another 4 hrs, the Pao2/Fio2 ratio deteriorated again in controls, but not in surfactant-treated animals. Total compliance fell by 50% after injury but was completely restored by surfactant treatment. Lung contusion increased the median number of neutrophils in bronchoalveolar lavage fluid from 2% to 30% of total cells and peaked >60% at 480 mins in the contused lungs of control pigs. Surfactant-treated pigs had 40% neutrophils at 480 mins without reaching significant difference to controls. The leukocyte neutral proteinase inhibitor increased to 500 ng/mL at 30 mins postinjury in the contused lungs and increased to 2000 ng/mL after surfactant treatment. CONCLUSIONS: Bilateral bronchoalveolar lavage with diluted surfactant can effectively improve lung function after experimental unilateral lung contusion in pigs.     

Histamine and methacholine aerosol bronchial challenge in awake guinea pigs

Cardiopulmonary responses to histamine and methacholine aerosol challenge were examined and compared in unanesthetized spontaneously breathing guinea pigs. All animals had surgically implanted intrapleural catheters and some had arterial or right heart catheters as well. Animals were placed in plethysmographs and exposed to ascending doses of aerosolized agonists. The provocative dose, i.e., the dose that caused a clear bronchospastic response, was defined as the concentration that increased intrapleural pressure to at least 20 cm H2O. Results showed that bronchospasm was characterized further by decreases in dynamic lung compliance and arterial PO2 and an increase in airway resistance. The accumulation of trapped gas in the lung, after challenge, measured in the excised collapsed lung correlated with the increase in intrapleural pressure and with the fall in lung compliance. Male guinea pigs between 3- and 15-weeks of age did not vary in sensitivity to histamine. Methacholine and histamine were equipotent and produced similar responses. Tachyphylaxis was not demonstrated for either compound. In addition, the provocative dose for the drugs remained stable on a day-to-day basis. These results offer insight into the nature of the bronchospastic response in guinea pigs and provide new data on response to methacholine.     

Effects of adenosine on extravascular lung water content in endotoxemic pigs.

OBJECTIVE: To investigate whether adenosine protects against endotoxin-induced increments in extravascular lung water content. DESIGN: Prospective, randomized, animal study. SETTING: University research laboratory. SUBJECTS: Twenty-one anesthetized juvenile pigs. INTERVENTIONS: The animals were divided into two groups subjected to endotoxin infusion: Endotoxin alone (n = 7), or endotoxin combined with adenosine infusion (n = 7) administered during the whole experimental period. Two other groups were exposed to anesthesia alone (n = 4) or adenosine infusion alone (n = 3), respectively. MEASUREMENTS AND MAIN RESULTS: Central hemodynamic variables and extravascular lung water, as assessed by the thermal dye dilution double indicator technique, were monitored. Plasma endothelin-1 concentrations were measured hourly. Extravascular lung water increased significantly in response to endotoxemia (p <.001) along with an increase in pulmonary microvascular pressure (P(mv) [p <.01]). Although the Pmv increased less in endotoxemic animals exposed to adenosine infusion, no intergroup difference was found. From 4 through 6 hrs, adenosine-treated pigs displayed only half of the extravascular lung water content of nontreated animals (p <.01). The latter did not differ from that of anesthetized controls receiving anesthesia or adenosine alone. Adenosine administered alone had no effect on P(mv). In pigs receiving adenosine alone, extravascular lung water content reached nadir after 3 hrs. In both endotoxin groups, plasma endothelin-1 concentration increased two-fold, peaking 4-6 hrs after the start of endotoxin infusion (p <.001). CONCLUSIONS: The endotoxin-induced increase in lung extravascular water was hampered by intravenously infused adenosine in the presence of a nonsignificantly reduced microvascular pressure. This leaves reduced microvascular permeability the most likely reason for the beneficial effect of adenosine.     

Optional active compliance chamber performance in a pulmonary artery-pulmonary artery configured paracorporeal artificial lung

INTRODUCTION: Our group has developed a paracorporeal artificial lung (PAL) attached in a pulmonary artery (PA) to PA in series configuration to address profound respiratory failure and serve as a bridge to transplant and/or recovery. We recently designed, developed and converted our passive pre-PAL compliance chamber to an active, synchronized, counterpulsating assist device to relieve right heart strain and offset increased work placed on the right ventricle when the PAL is attached. In this study, we evaluated the safety and performance of both a valved and non-valved optional active compliance chamber (OACC) in a PA-PA PAL for right heart assistance in normal adult sheep. METHODS: Eleven sheep (30-50 kg) were divided into non-valved OACC (n = 6) and valved (n = 5) OACC groups. To mimic pulmonary hypertension, a C-clamp was placed distal to the OACC-PAL and occluded until a 20% decrease in cardiac output (CO) was achieved. The OACC was activated, and right ventricular pressure (RVP), pulmonary artery pressure (PAP), mean arterial pressure (MAP) and CO were recorded. RESULTS: All eleven animals tolerated the implantation of the OACC PAL. Activation of the OACC resulted in a significant increase in CO. Systolic and diastolic right ventricular pressure decreased in both groups. Lastly, counterpulsation increased the mean PAP in all animals and peak PAP reached 89 mmHg. Despite providing right heart assistance, synchronizing the counterpulsation was technically difficult, and the high peak PA pressures resulted in anastomotic bleeding in all animals and anastomotic breakdown in 4/11 animals. CONCLUSIONS: An OACC PAL perfused by the right ventricle applied in series with the pulmonary circulation reduces ventricular load and improves cardiac efficiency. These preliminary data suggest the potential of an artificial lung in unloading the strained right ventricle and acting as a bridge to transplantation. The augmented peak PA pressures, resulting in bleeding and anastomotic breakdown, and complexity in synchronizing the cardiac cycle with the pulsations of the augmented OACC, compromise this configuration.     

Smoke inhalation causes a delayed increase in airway blood flow to primarily uninjured lung areas

Objective Single lung inhalation injury causes tissue damage to the contralateral lung. We therefore examined airway blood flow after smoke inhalation in chronic instrumented sheep to get further information about the underlying pathophysiology.Design/patients The right lung and lower trachea of 5 animals were smoke-exposed, while their left lung was air-insufflated using a split ventilation technique. Three animals, where both lungs were only air-insufflated, served as controls. Blood flow to the airway was measured using a labeled microsphere technique. All animals were studied for 24 h following smoke inhalation. Then they were sacrificed and their tissues harvested.Results The airway blood flow to the smoke-exposed lung was elevated 11-fold immediately after inhalation injury. The bronchial blood flow to the air insufflated lung became significantly elevated 24 h post-smoke, although to a lesser extent. The control animals did not show any changes of bronchial blood flow during the observation time.Conclusions Damage to one lung can lead to pathophysiologic changes in the contralateral lung. This response appears to be mediated by hematogenous factors.Supported by grant # GM33324, # HL37411, and grant from the Sealy Smith Foundation and the Shriners of North America     

维和部队二级医院伤员空运后送前的护理

笔者报道中国首支维和医疗队驻刚果(金)第5战区二级医院13例伤员空运后送前的护理。总结后送前掌握后送标准及时机、后送程序、后送人员职责,做好伤病员的心理准备、生命体征的评估、充分物品准备以及从医院至机场后送过程中的护理,为我军伤病员分级救治和后送提供借鉴。     

Use of ultrasound to enhance nonviral lung gene transfer in vivo

We have assessed if high-frequency ultrasound (US) can enhance nonviral gene transfer to the mouse lung. Cationic lipid GL67/pDNA, polyethylenimine (PEI)/pDNA and naked plasmid DNA (pDNA) were delivered via intranasal instillation, mixed with Optison microbubbles, and the animals were then exposed to 1 MHz US. Addition of Optison alone significantly reduced the transfection efficiency of all three gene transfer agents. US exposure did not increase GL67/pDNA or PEI/pDNA gene transfer compared to Optison-treated animals. However, it increased naked pDNA transfection efficiency by approximately 15-fold compared to Optison-treated animals, suggesting that despite ultrasound being attenuated by air in the lung, sufficient energy penetrates the tissue to increase gene transfer. US-induced lung haemorrhage, assessed histologically, increased with prolonged US exposure. The left lung was more affected than the right and this was mirrored by a lesser increase in naked pDNA gene transfer, in the left lung. The positive effect of US was dependent on Optison, as in its absence US did not increase naked pDNA transfection efficiency. We have thus established proof of principle that US can increase nonviral gene transfer, in the air-filled murine lung.     

Normal fetal lung volume measured with three-dimensional ultrasound.

OBJECTIVES: To construct reference intervals for fetal lung volumes measured longitudinally using three-dimensional (3D) ultrasound, and to evaluate the effect of gender on lung size. METHODS: This was a prospective, longitudinal study in the obstetric outpatient department of the VU University Medical Center, Amsterdam. Seventy-eight women with uncomplicated pregnancies were scanned three to four times at gestational ages of 18-34 weeks. 3D models of the lung were constructed using the ultrasound machine's software. After the infants were delivered the entire group was reanalyzed with regard to fetal gender. Centiles for the lung volumes of the entire group and for each gender separately were estimated using multilevel modeling. RESULTS: Charts and tables of right and left fetal lung volumes, using gestational age and estimated fetal weight as the independent variables, are presented. There was a significant difference in lung volume between male and female fetuses at each gestational age. Charts and tables of right and left fetal lung volumes for each gender at gestational ages of 18-34 weeks are also presented. CONCLUSIONS: We present valid references for volumetric measurements of the right and left fetal lungs in male and female fetuses. The feasibility and reliability of fetal lung volume measurements using 3D ultrasound is good.