Inhaled and intravenous corticosteroids both attenuate chlorine gas-induced lung injury in pigs

BACKGROUND: The accidental release of chlorine gas is a constant threat in urban areas. The purpose of this randomized, blinded, controlled experiment was to examine the effects of post-injury administration of inhaled or intravenous corticosteroid in chlorine gas-injured pigs followed for 23 h. METHODS: Anaesthetized, ventilated pigs (n = 24) in the prone position were exposed to chlorine gas (400 parts per million in air) (1160 mg/m3) for 15 min, then randomly allocated to receive inhaled budesonide (BUD) and intravenous placebo, intravenous betamethasone (BETA) and inhaled placebo or inhaled and intravenous placebo. Haemodynamics, gas exchange and lung mechanics were evaluated for 23 h after exposure to chlorine gas. RESULTS: Airway and pulmonary artery pressures increased and arterial oxygenation fell sharply (from 13.5 +/- 0.8 to 6.7 +/- 0.9 kPa, P < 0.001) after chlorine gas exposure. These immediate changes were followed by a gradual improvement over 5-7 h to a stable level of dysfunction for the rest of the experiment in placebo animals. Arterial oxygen tension, pulmonary vascular resistance and airway pressure recovered faster and more completely in the budesonide and betamethasone groups than in the placebo group (P < 0.01). Lung wet weight to dry weight ratios were greater in the placebo group than in the budesonide and betamethasone groups (6.34 +/- 0.59 vs. 5.56 +/- 0.38 and 5.53 +/- 0.54, respectively, P < 0.05). There was a trend towards lower histological injury scores compared with placebo in animals that received budesonide (P = 0.05) or betamethasone (P = 0.07). CONCLUSION: Treatment of chlorine gas lung injury with nebulized budesonide or intravenous betamethasone had similar positive effects on recovery of lung function.     

Effects of inhalation of corticosteroids immediately after experimental chlorine gas lung injury

BACKGROUND: To assess the effects of treatment with nebulized corticosteroids immediately after chlorine gas injury. METHODS: Eighteen anesthetized and mechanically ventilated pigs were exposed to chlorine gas (140 ppm for 10 minutes) and observed for 6 hours. Nine pigs were treated with nebulized beclomethasone-dipropionate 20 microg/kg (BDP group), and nine pigs were given no treatment (control group). RESULTS: All animals developed severe pulmonary dysfunction. The initial decrease in PaO2 was similar in both groups, but BDP-treated animals improved whereas control animals deteriorated (p < 0.005; analysis of variance). Pulmonary vascular resistance increased in both groups but less in the BDP group (p < 0.01). Lung-thorax compliance was better preserved in the BDP group (p < 0.01), and oxygen delivery was significantly better in the BDP group (p < 0.01). One animal died in the BDP group, as did three animals in the control group. CONCLUSION: Immediate treatment with nebulized BDP improved pulmonary and cardiovascular function after experimental chlorine gas injury.     

Budesonide and terbutaline or terbutaline alone in children with mild asthma: effects on bronchial hyperresponsiveness and diurnal variation in peak flow.

The effects of treatment with budesonide (200 micrograms twice daily) and terbutaline (500 micrograms four times daily) has been compared with the effects of placebo and terbutaline in 27 children with mild asthma, aged 7-14 years, in a double blind, randomised placebo controlled study over eight weeks. Bronchial responsiveness (PC20 histamine), lung function, the amplitude of diurnal variation in peak expiratory flow (PEF), and symptom scores were measured. Baseline FEV1 was over 70% predicted and PC20 histamine less than 8 mg/ml. Twelve children were treated with budesonide and terbutaline and 15 with placebo and terbutaline. After four and eight weeks of treatment the change in PC20 was significantly greater after budesonide and terbutaline than after terbutaline alone by 2.1 (95% CI 0.5-3.8) and 1.3 (95% CI 0.1-2.5) doubling doses respectively. Mean FEV1 did not change in either group. The change in afternoon and nocturnal PEF was significantly greater after budesonide and terbutaline than after terbutaline alone. The amplitude of diurnal variation in PEF did not change significantly in either group. Peak flow reversibility decreased in the budesonide group. There were no differences between treatments for cough and dyspnoea, but wheeze improved in the budesonide group. The children with mild asthma treated with budesonide and terbutaline showed improvement in bronchial responsiveness, afternoon and nocturnal PEF, and symptoms of wheeze and a fall in peak flow reversibility by comparison with those who received terbutaline alone.     

Effect of regular terbutaline on the airway response to inhaled budesonide.

BACKGROUND: The rebound increase in bronchial reactivity and fall in forced expiratory volume in one second (FEV1) following treatment with beta agonists seen in several studies has occurred regardless of concurrent steroid therapy. Little is known about the effect of adding beta agonists to corticosteroids, but in a recent study regular treatment with terbutaline appeared to reduce some of the beneficial effects of budesonide. The effects of budesonide alone and in combination with regular terbutaline treatment on lung function, symptom scores, and bronchial reactivity were therefore examined. METHODS: Sixteen subjects with mild stable asthma inhaled budesonide 800 micrograms twice daily for two periods of 14 days with terbutaline 1000 micrograms three times daily or placebo in a double blind crossover fashion. FEV1 and the dose of histamine or adenosine monophosphate (AMP) causing a 20% fall in FEV1 (PD20) were measured before and 12 hours after the final dose of treatment, and changes from baseline were compared. Seven day mean values for daily morning and evening peak expiratory flow (PEF) values, symptom scores, and rescue medication were compared before and during treatment. RESULTS: Morning and evening PEF rose more with budesonide plus terbutaline than with budesonide alone, with a mean difference of 19 l/min occurring in the evening (95% confidence interval (CI) 2 to 36). There was no difference in symptom scores during treatment. Following treatment the mean increase in FEV1 was 150 ml higher with budesonide alone (95% CI-10 to 300). There was no difference between treatments in change in histamine and AMP PD20. CONCLUSIONS: Evening PEF was greater when budesonide was combined with regular terbutaline. There was no evidence of a difference in bronchial reactivity following the two treatment regimens. The findings of a previous study were not confirmed as the reduction in FEV1 after budesonide and terbutaline was smaller and not statistically significant. Further work is needed to determine whether this disparity in findings in the two studies is due to a type 2 statistical error in this study or a spurious finding in the previous study.     

Randomised trial of an inhaled β2 agonist, inhaled corticosteroid and their combination in the treatment of asthma

BACKGROUND: Although many asthmatic patients are treated with a combination of beta2 agonist and corticosteroid inhalers, the clinical effects of combining the drugs are unknown. Studies on the early asthmatic response to allergen suggest that beta2 agonists may reduce the benefit of inhaled corticosteroids. A study of the effects of combining the drugs on asthma control was undertaken. METHODS: Sixty one subjects with mild to moderate asthma were randomised to a double blind crossover comparison of inhaled budesonide (200-400 microg twice daily), terbutaline (500-1000 microg four times daily), combined treatment, and placebo. Each treatment was given for six weeks following a four week washout period. Ipratropium was used for symptom relief. Treatments were ranked from worst (1) to best (4) based on need for oral steroid, mean morning peak flow, nocturnal awakening, ipratropium use, and asthma symptoms. Lung function and bronchial hyperresponsiveness were measured before and after each treatment. RESULTS: Evaluable data for all four treatments were obtained from 47 subjects. The mean rank of each treatment was: placebo = 2.05; terbutaline = 2.13; budesonide = 2.48; combined treatment = 3.34. Combined treatment was ranked significantly better than any other treatment (p<0.01). Mean (95% CI) morning and evening peak flows were 14 (5 to 23) and 24 (15 to 34) l/min higher, respectively, during combined treatment than during budesonide, and 27 (17 to 37) and 15 (7 to 23) l/min higher than during terbutaline. Asthma symptoms tended to be least frequent during combined treatment but were not significantly different from budesonide alone. There was no significant difference between combined treatment and budesonide alone for lung function and bronchial hyperresponsiveness. CONCLUSIONS: In this group of mild to moderate asthmatic subjects the combination of beta2 agonist and corticosteroid gave better asthma control than either treatment alone. There was no evidence that regular beta2 agonist treatment impaired the beneficial effect of inhaled corticosteroid.     

Combining partial liquid ventilation and prone position in experimental acute lung injury.

BACKGROUND: Partial liquid ventilation (PLV) and prone position can improve arterial oxygen tension (PaO2) in acute lung injury (ALI). The authors evaluated additive effects of these techniques in a saline lung lavage model of ALI. METHODS: ALI was induced in 20 medium-sized pigs (29.2+/-2.5 kg body weight). Gas exchange and hemodynamic parameters were determined in both supine and prone position in all animals. Thereafter, one group was assigned to PLV with two sequential doses of 15 ml/kg of perfluorocarbon (n = 10); the second group was assigned to gaseous ventilation (n = 10). Gas-exchange and hemodynamic parameters were determined at corresponding time points in both groups in prone and supine position. RESULTS: In the PLV group, positioning the animals prone resulted in an increase of PaO2 prior to PLV and during PLV with both doses of perfluorocarbon when compared to ALI. PLV in supine position was only effective if 30 ml/kg of perfluorocarbon was applied. In the gaseous ventilation group, PaO2 increased reproducibly compared with ALI when the animals were turned prone. A significant additive improvement of arterial oxygenation was observed during combined therapy with 30 ml/kg of perfluorocarbon and prone position in the PLV group compared with either therapy alone. CONCLUSIONS: The authors conclude that combining PLV with prone position exerts additive effects on pulmonary gas exchange in a saline lung lavage model of ALI in medium-sized pigs.     

开肺陷胸汤对大鼠胰源性肺损伤的防治效应

目的：在制备大鼠胰源性肺损伤动物模型基础上给予中药治疗，动态观察血氧分压及二氧化碳分压变化，并对肺脏进行病理学分析。方法：实验分为模型组及中药治疗组,72h后观察肺脏病理变化及不同时间血气分析。结果：治疗组肺脏病理改变明显减轻（P＜0．05）；治疗组72h血氧分压明显高于模型组（P＜0．01），血二氧化碳分压明显低于模型组（P＜0．01）。结论：在胰源性肺损伤发病过程中，血氧分压及二氧化碳分压的变化直接反应出肺损伤病理改变的严重程度，治疗组随着氧分压升高，二氧化碳分压降低，标志着肺脏病理改变明显减轻。     

Surfactant and inhaled nitric oxide in rats alleviate acute lung injury induced by intestinal ischemia and reperfusion.

BACKGROUND: Respiratory distress and acute lung injury (ALI) are severe complications of intestinal ischemia and reperfusion injury (I/R). The authors hypothesize that a combined surfactant and inhaled nitric oxide (iNO) may alleviate I/R-induced ALI. METHODS: Adult rats (body weight 285 to 315 g, n = 45) were allocated randomly to either a negative control group (N-Control, n = 9) with only sham laparotomy, or groups (n = 9 each) for induction of I/R by occlusion of superior mesenteric artery, followed by treatment with (1) surfactant at 100 mg/kg (Surf), (2) iNO at 20 ppm (NO), (3) both surfactant and iNO (SNO), or (4) no surfactant no iNO (a positive control, P-Control). Mechanical ventilation was provided for 120 minutes with variable peak insufflation pressure and FIO2 to achieve adequate arterial pH, PaO2, and PaCO2. Blood gas values, dynamic lung compliance (Cdyn), and airway resistance (Raw) were measured during the 2-hour treatment. Lung wet-to-dry weight ratio (W/D), histopathology, and morphometric analysis of alveolar expansion (V(V)) were determined at the end of the experiment. RESULTS: After 120 minutes of treatment, the SNO group had the highest PaO2 and Cdyn values, close to that of the N-Control group. The Surf, NO, and SNO groups had higher V(V) and lower CV (V(V)) values than the P-Control, but modest decrease of W/D values. The NO group had moderately improved PaO2 but Cdyn and V(V) were as low as that of the P-Control. The lungs of the SNO group had significantly alleviated edema and neutrophil infiltration compared with the P-Control. CONCLUSIONS: The combined surfactant and iNO treatment alleviated rat ALI induced by I/R, and exerted effects better than the use of surfactant or iNO alone.     

No early respiratory benefit with CVVHDF in patients with acute renal failure and acute lung injury.

BACKGROUND: There is debate as to whether, in patients with acute lung injury, continuous renal replacement therapy has beneficial effects on pulmonary gas exchange by mechanisms other than fluid removal. Because continuous renal replacement therapy is associated with potential morbidity and mortality, it seems unethical to perform a randomized trial in patients with acute lung injury without renal failure. Therefore, the effects of continuous venovenous haemodiafiltration with zero volume balance on gas exchange were evaluated in patients with acute renal failure and acute lung injury. Because haemofilter conditions should be comparable between patients, we opted for an evaluation of the effects during a 24-h period. Results of this trial can guide future studies in non-renal patients with acute lung injury. METHODS: In all 37 patients with acute renal failure and acute lung injury, treated with continuous venovenous haemodiafiltration with zero fluid balance during a 1 year period, ventilatory and haemodynamic parameters were measured every 8 h during the 24 h preceding therapy and during the first 24 h of therapy. RESULTS: We found a slight, although not statistically significant, increase in the PaO(2)/FIO(2) ratio and the oxygenation index, in the total group of patients, and in the subgroups of patients with acute lung injury of extrapulmonary and pulmonary causes. CONCLUSIONS: During the first 24 h of treatment, continuous venovenous haemodiafiltration with zero volume balance did not result in a significant improvement of the respiratory status in patients with acute renal failure and acute lung injury, nor in the subgroups of patients with acute lung injury with extrapulmonary causes.     

Effects of prone and supine posture on cardiopulmonary function after experimental chlorine gas lung injury

BACKGROUND: Chlorine gas may induce severe acute lung injury. Improvement of pulmonary gas exchange in patients and animals with acute lung injury nursed in the prone position was observed in recent years. The purpose of this study was to evaluate the effects of prone and supine positions on pulmonary and cardiovascular functions following experimental chlorine gas lung injury. METHODS: Twenty anesthetized and mechanically ventilated pigs were exposed to chlorine gas (400 p.p.m. in air) for 20 min in the supine position, then assigned randomly to ventilation in the supine or prone positions (n=10 in each group). Hemodynamics, gas exchange, lung mechanics and oxygen transport were evaluated for 5 h. RESULTS: All animals showed severe pulmonary dysfunction immediately after chlorine gassing with a threefold increase in pulmonary vascular resistance index, a drop in arterial oxygenation (12.3+/-1.3 kPa to 5.4+/-0.7 kPa) and a fall in lung-thorax compliance (22+/-1 ml cmH2O-1 to 8+/-2 ml cmH2O-1). Venous admixture (Qs/Qt) improved in animals in the prone position while there was no change in the supine position (prone 32+/-11% vs. supine 42+/-9% at 5 h,P<0.05). Lung-thorax compliance improved significantly with time in the prone group only (P<0.01). Oxygen delivery increased significantly in prone animals compared with animals nursed in the supine posture (P<0.001). CONCLUSION: Immediate prone positioning after chlorine gas injury not only inhibited deterioration of gas exchange but was also associated with improved pulmonary function and oxygen transport.     

Effect of inhaled prostacyclin in combination with almitrine on ventilation-perfusion distributions in experimental lung injury

BACKGROUND: Inhaled prostacyclin and intravenous almitrine have both been shown to improve pulmonary gas exchange in acute lung injury (ALI). This study was performed to investigate a possible additive effect of prostacyclin and almitrine on pulmonary ventilation-perfusion (VA/Q) ratio in ALI compared with inhaled prostacyclin or intravenous almitrine alone. METHODS: Experimental ALI was established in 24 pigs by repeated lung lavage. Animals were randomly assigned to receive either 25 ng.kg(-1).min(-1) inhaled prostacyclin alone, 1 microg.kg(-1).min(-1) almitrine alone, 25 ng.kg(-1).min(-1) inhaled prostacyclin in combination with 1 microg.kg(-1).min(-1) almitrine, or no specific treatment (controls) for 30 min. For each intervention, pulmonary gas exchange and hemodynamics were analyzed and VA/Q distributions were calculated using the multiple inert gas elimination technique. The data was analyzed within and between the groups by analysis of variance for repeated measurements, followed by the Student-Newman-Keuls test for multiple comparison when analysis of variance revealed significant differences. RESULTS: All values are expressed as mean +/- SD. In controls, pulmonary gas exchange, hemodynamics, and VA/Q distribution remained unchanged. With prostacyclin alone and almitrine alone, arterial oxygen partial pressure (PaO2) increased, whereas intrapulmonary shunt (QS/QT) decreased (P < 0.05). Combined prostacyclin and almitrine also increased PaO2 and decreased QS/QT (P < 0.05). When compared with either prostacyclin or almitrine alone, the combined application of both drugs revealed no additional effect in gas exchange or VA/Q distribution. CONCLUSIONS: The authors conclude that, in this experimental model of ALI, the combination of 25 ng.kg(-1).min(-1) prostacyclin and 1 microg.kg(-1).min(-1) almitrine does not result in an additive improvement of pulmonary gas exchange or VA/Q distribution when compared with prostacyclin or almitrine alone.     

Effects of short-term inhaled nitric oxide on interleukin-8 release after single-lung transplantation in pigs.

BACKGROUND: Lung transplantation has evolved to become an effective treatment for a variety of end-stage lung diseases. However, severe reperfusion injury is still a major cause for postoperative morbidity and mortality. Although lung reperfusion injury is complex and has not been fully comprehended yet, neutrophil infiltration and cytokine activation have been postulated to play a main role. Recent studies showed that nitric oxide (NO) therapy has salutary effects on lung chronic and acute pathologies because it inhibits interleukin-8 (IL-8) release, but no data have been found on its effects during organ harvest. The aim of this study was to assess whether low doses of inhaled NO pre-treatment at the time of harvesting improves allograft function during early reperfusion in a porcine model. METHODS: Twenty-two Landrace pigs were randomly assigned to NO-treated and control groups. In NO-treated pigs, NO at 20 ppm was administered 30 min before harvest. During the early allograft reperfusion period IL-8 content, dynamic and static compliance and gas exchange (Pa/FiO2 and PaO2) were measured in both control and NO-treated lungs. RESULTS: Pre-treatment with NO at the time of harvesting showed improvement of allograft function in terms of dynamic (92 +/- 8% in NO vs 72 +/- 7% in the control group, p < .05) and static (83 +/- 8% in NO vs 63 +/- 7% in the control group, p < 0.05) compliance and gas exchange (PaO2: 96 +/- 4% in NO vs 74 +/- 4.5% in the control group, p < 0.01; Pa/FiO2: 97 +/- 5% in NO vs 74 +/- 5% in the control group, p < 0.01) by diminishing IL-8 (66.5 +/- 4.7 pg/ml in NO versus 208 +/- 43 pg/ml in the control group, p < 0.05) release in pigs. CONCLUSION: These results show for the first time that NO pre-treatment at the time of harvesting reduces allograft reperfusion injury in part due to its effects on IL-8 release.     

Effect of PEEP and inhaled nitric oxide on pulmonary gas exchange during gaseous and partial liquid ventilation with small volumes of perfluorocarbon

BACKGROUND: Partial liquid ventilation, positive end-expiratory pressure (PEEP) and inhaled nitric oxide (NO) can improve ventilation/perfusion mismatch in acute lung injury (ALI). The aim of the present study was to compare gas exchange and hemodynamics in experimental ALI during gaseous and partial liquid ventilation at two different levels of PEEP, with and without the inhalation of nitric oxide. METHODS: Seven pigs (24+/-2 kg BW) were surfactant-depleted by repeated lung lavage with saline. Gas exchange and hemodynamic parameters were assessed in all animals during gaseous and subsequent partial liquid ventilation at two levels of PEEP (5 and 15 cmH2O) and intermittent inhalation of 10 ppm NO. RESULTS: Arterial oxygenation increased significantly with a simultaneous decrease in cardiac output when PEEP 15 cmH2O was applied during gaseous and partial liquid ventilation. All other hemodynamic parameters revealed no relevant changes. Inhalation of NO and instillation of perfluorocarbon had no additive effects on pulmonary gas exchange when compared to PEEP 15 cmH2O alone. CONCLUSION: In experimental lung injury, improvements in gas exchange are most distinct during mechanical ventilation with PEEP 15 cmH2O without significantly impairing hemodynamics. Partial liquid ventilation and inhaled NO did not cause an additive increase of PaO2.     

Combining Partial Liquid Ventilation and Prone Position in Experimental Acute Lung Injury

Background: Partial liquid ventilation (PLV) and prone position can improve arterial oxygen tension (PaO2) in acute lung injury (ALI). The authors evaluated additive effects of these techniques in a saline lung lavage model of ALI.

Methods: ALI was induced in 20 medium-sized pigs (29.2 +/- 2.5 kg body weight). Gas exchange and hemodynamic parameters were determined in both supine and prone position in all animals. Thereafter, one group was assigned to PLV with two sequential doses of 15 ml/kg of perfluorocarbon (n = 10); the second group was assigned to gaseous ventilation (n = 10). Gas-exchange and hemodynamic parameters were determined at corresponding time points in both groups in prone and supine position.

Results: In the PLV group, positioning the animals prone resulted in an increase of PaO2 prior to PLV and during PLV with both doses of perfluorocarbon when compared to ALI. PLV in supine position was only effective if 30 ml/kg of perfluorocarbon was applied. In the gaseous ventilation group, PaO2 increased reproducibly compared with ALI when the animals were turned prone. A significant additive improvement of arterial oxygenation was observed during combined therapy with 30 ml/kg of perfluorocarbon and prone position in the PLV group compared with either therapy alone.     

Acute respiratory distress syndrome secondary to inhalation of chlorine gas in sheep

BACKGROUND: Toxic industrial chemicals (TICs) are potential terrorist weapons. Several TICs, such as chlorine, act primarily on the respiratory tract, but knowledge of the pathophysiology and treatment of these injuries is inadequate. This study aims to characterize the acute respiratory distress syndrome (ARDS) caused by chlorine gas (Cl2) inhalation in a large-animal model. METHODS: Anesthetized female sheep were ventilated with 300 L of a Cl2/air/oxygen mixture for 30 minutes. In phase 1 (n = 35), doses were 0 ppm (Group 1, n = 6); 120 ppm (Group 2, n = 6); 240 to 350 ppm (Group 3, n = 11); and 400 to 500 ppm (Group 4, n = 12). In phase 2 (n = 17), doses were 0 ppm (Group 5, n = 5); 60 ppm (Group 6, n = 5); and 90 ppm (Group 7, n = 7), and the multiple inert gas elimination technique (MIGET) was used to characterize the etiology of hypoxemia. Computed tomography (CT) scans were performed daily for all animals. RESULTS: In Phase 1, lung function was well maintained in Group 1; Cl2 caused immediate and sustained acute lung injury (PaO2-to-FiO2 ratio, PFR<3.0) in Group 2 and ARDS (PFR<2.0) in Groups 3 and 4. All animals in Groups 1 and 2 survived 96 hours. Kaplan-Meier analysis showed dose-related differences in survival (log-rank test, p < 0.0001). Logistic regression identified 280 ppm as the lethal dose 50%. CT and histopathology demonstrated lesions of both small airways and alveoli. In Phase 2, MIGET showed diversion of blood flow from normal to true-shunt lung compartments and, transiently, to poorly ventilated compartments. CONCLUSIONS: Cl2 causes severe, dose-related lung injury, with features seen in both smoke inhalation and in ARDS secondary to systemic disease. This model will be used to test new therapeutic modalities.     

Almitrine bismesylate and oxygen therapy in hypoxic cor pulmonale.

The effect of oral treatment with the thiazine derivative almitrine bismesylate was studied in 28 patients with chronic obstructive pulmonary disease and arterial hypoxaemia receiving long term domiciliary oxygen therapy in a placebo controlled, double blind crossover trial. The initial treatment was given for three months and the second for two months. Because almitrine had an unexpectedly prolonged washout effect crossover analysis could not be performed; data from the placebo treatment administered in the second arm of the trial were used to calculate the half life of almitrine. Nine patients were withdrawn from the study (5 almitrine, 4 placebo). Patients' tolerance of the drug was good. The estimated plasma half life of almitrine was 20.5 days, considerably longer than previously reported. Almitrine caused a significant improvement in arterial oxygen tension (PaO2) with a mean maximum increase of 0.7 kPa at a plasma concentration of 500 ng/ml. Higher plasma concentrations were not associated with any further increase in PaO2. There was no significant effect on arterial carbon dioxide tension (PaCO2). In a second, acute study at the end of each arm of the chronic trial nine patients were subjected to increasing oxygen delivery rates (2, 4, and 6 l/min) for 90 minutes or until blood gas concentrations plateaued. Almitrine increased PaO2 in a dose dependent fashion at all delivery rates, but the effect diminished as PaO2 approached normoxic levels. There was no significant effect on PaCO2. Almitrine treatment results in a significant improvement in PaO2 over that achieved by oxygen alone, an effect that diminishes at high flow rates. Whether this is of clinical benefit is not known. In view of the prolonged half life revised dosage schedules are required.     

Effects of the beta-2 receptor agonist terbutaline on hemodynamics and gas-exchange in endotoxin shock

The effects of the beta-2 receptor agonist, terbutaline, on hemodynamics and gas-exchange were evaluated in sheep exposed to endotoxin shock. Terbutaline was not given until signs of shock and lung injury had developed. Twenty sheep were anesthetized and ventilated without PEEP. After 90 min of stabilization (t = 0) all animals received E. coli endotoxin 10 micrograms/kg by i.v. infusion during 15 min. Thirty minutes later (t = 30) 10 animals (group TER) received i.v. infusion of terbutaline, 20 micrograms/kg/h, during 4 hours, while the other 10 served as controls (group S). The endotoxin infusion resulted in marked increase in pulmonary artery pressure (PAP) and a significant decrease in mean arterial pressure (MAP), respiratory compliance, arterial oxygen tension (PaO2) and oxygen delivery index (DO2) in both groups (t = 15 and t = 30). After 4 hours the PAP had decreased significantly in the terbutaline treated animals, but remained high in the controls (p less than 0.01). Also, MAP, PaO2, DO2 and compliance improved significantly in the terbutaline treated animals. The wet to dry weight ratio of the lungs was 4.85 +/- 0.2 in the terbutaline treated and 5.35 +/- 0.5 in the controls (p less than 0.05). It was concluded that terbutaline treatment improves gas-exchange and hemodynamics in sheep exposed to endotoxin shock.     

Aerosolized surfactant and dextran for experimental acute respiratory distress syndrome caused by acidified milk in rats

BACKGROUND: Inhibition of pulmonary surfactant by plasma-derived proteins is an important pathogenetic factor of acute respiratory distress syndrome (ARDS). Inhalation of aerosolized surfactant may be suitable for early treatment of ARDS. However, requirement of a high dose is a drawback. Because dextran reverses surfactant inhibition, we examined whether dextran improves the therapeutic effects of aerosolized surfactant in rats with experimental ARDS. METHODS: Acidified milk (pH 1.8, 1.5 ml kg(-1)) was injected into the trachea of the rats ventilated with pure oxygen using 2.45 kPa peak inspiratory pressure and 0.74 kPa positive end-expiratory pressure. When PaO2 decreased to <13 kPa, the rats were assigned to four groups: control group (n = 8), receiving no material; D-only group (n = 6), receiving aerosolized dextran for 45 min; S-only group (n = 8), receiving aerosolized modified natural surfactant (MNS) for 30 min; and S-plus-D group (n = 9), receiving aerosolized MNS for 30 min followed by aerosolized dextran for 15 min. RESULTS: In the control group and D-only groups, the mean PaO2 remained at <10 kPa for 180 min. In the S-only and S-plus-D groups, the PaO2 increased to 50 kPa (P < 0.01 vs. untreated). The PaO2 of the surfactant-only group gradually decreased to <17 kPa at 180 min, whereas the PaO2 of the S-plus-D group was maintained at >38 kPa for 180 min (P < 0.01 vs. S-only group). CONCLUSION: Inhalation of aerosolized dextran potentiates the effects of aerosolized surfactant by prolonging the therapeutic response.     

Effect of terbutaline on alveolar liquid clearance after oleic acid-induced lung injury in rats

To investigate whether terbutaline affects alveolar liquid deorance after oleic acid-induced lung injury in rats. Methods ： Forty healthy Wistor rats （ weighing 250- 280 g） were randomly divided into five groups （ n = 8 in each group ） ： the normal control group （ control group ）, oleic acid injury group （injury group）, group （terbutaline group ）, terbutaline plus amiloridetreated group （ terbutaline ＋ amiloride group ） and terbutaline plus ouabaln-treated group （terbutaline ＋ ouabaln group）. Acute lung injury model was induced by intravenous oleic acid （0. 25 ml/kg body weight）. 24 hours later, 1.5 μCi^125 I-labeled 5% albumin solution （5 ml/kg body weight） was dripped into the lungs through trachea. The alveolar liquid clearance rate, extravascular lung water content, and arterial blood gas were measured 1 hour thereafter. Results： At24 hours after infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia,with the alveolar liquid clearance rate decreased by 49. 2 % and the extravascnlar lung water content elevated by 47.9%. Compared with the rats in the injury group, terbutaline （ 10^-4 mol/L ） significantly increased the alveolar liquid clearance rate, decreased the extravascular lung water content and improved hypoxemia. The effect of terlmtaUne was partly blocked by amiloride and ouabain, which were inhibitors of sodium transport. Terbutaline increased the alveolar liquid clearance rate by 63.7 %, and amiloride and ouabain reduced the alveolar liquid clearance rate by 54.7 % and 56. 8 %, respectively. Conclusions： Terbutaline can accelerate alveolar liquid clearance through increasing sodim transport to attenuate pulmonary edema, thus improving gas exchange, which may have therapeutical effect on pulmonary edema after acute lung injury.     

Hemodynamic and oxygenation changes of combined therapy with inhaled nitric oxide and inhaled aerosolized prostacyclin

OBJECTIVE: To evaluate hemodynamic and oxygenation changes of combined therapy with inhaled nitric oxide (iNO) and inhaled aerosolized prostcyclin (IAP) during lung transplantation. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Ten patients scheduled for lung transplantation. INTERVENTIONS: Ten patients, with a mean age of 38 years (range, 24 to 56 years), were scheduled for lung transplantation (2 single-lung transplantations and 8 double-lung transplantations). During first lung implantation with single-lung perfusion and ventilation, hemodynamic and oxygenation data were analyzed in 3 phases: (1) baseline, 5 minutes after pulmonary artery clamping; (2) inhaled NO phase, 15 minutes after inhaled NO administration (20 ppm) in 100% oxygen; and (3) IAP-inhaled NO phase, 15 minutes after combined administration of inhaled NO (20 ppm) and IAP (10 ng/kg/min) in 100% oxygen. MEASUREMENTS AND MAIN RESULTS: During the inhaled NO phase, reductions of mean pulmonary arterial pressure (p < 0.05) and intrapulmonary shunt (p < 0.05) were noted. After the start of prostacyclin inhalation, a further decrease in mean pulmonary arterial pressure (p < 0.05) was observed. PaO2/FIO2 increased during the IAP-inhaled NO phase (p < 0.05), whereas intrapulmonary shunt decreased (p < 0.05). CONCLUSION: This study confirms the action of inhaled NO as a selective pulmonary vasodilator during lung transplantation. Combined therapy with IAP and inhaled NO increases the effects on pulmonary arterial pressure and oxygenation compared with inhaled NO administered alone without any systemic changes.