The effect of Borago officinalis on the signaling pathway of the NLRP3 inflammasome complex, TLR4 and some inflammatory cytokines in type II diabetic patients with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which the lungs become severely inflamed, causing the alveoli to constrict or fill with fluid, which prevents the lungs from functioning properly. This disease becomes more dangerous when it occurs in patients with diabetes. Because of the clinical condition of these patients, it is not possible to treat them with usual medicines. One of the best options for treating these people is to use herbs. Borage (Borago officinalis) is a medicinal herb that, in addition to its anti-inflammatory properties, is also able to control blood sugar. Therefore, in the current study, the effect of borage oil was considered on the signaling pathway of the NLRP3 inflammasome complex, TLR4, and serum levels of inflammatory cytokines (IL-1? and IL-18) in type II diabetic patients with ARDS. For this purpose, 25 diabetic type II patients with ARDS were divided into three groups by ARDS Berlin Definition. Then, after providing the demographic and clinical characteristics of the patients, they were treated with 30 mg/day borage oil for seven days. The expression of NLRP3 and TLR4 genes (by Real-time PCR technique) and serum levels of IL-1? and IL-18 (by ELISA test) were evaluated before and after treatment with borage oil through blood samples taken from patients. The results showed that serum levels of inflammatory cytokines (IL-1? and IL-18), NLRP3 gene, and TLR4 gene were significantly decreased in diabetic type II patients with mild ARDS by treating with borage oil. IL-1? serum level and TLR4 were significantly decreased in diabetic type II patients with moderate ARDS. But there was not any significant decrease or increase in IL-1?, IL-18, NLRP3 gene, and TLR4 gene in diabetic type II patients with severe ARDS after 7 days of treatment with borage oil. According to the obtained results, borage oil can act as a double-edged blade. Thus, in the early and middle stages of ARDS, borage oil can be effective in reducing the inflammasome pathway of inflammation and also reduce blood sugar levels in these diabetic patients. But in the severe stage of ARDS, it not only does not help to treat the ARDS; it also increases systolic and diastolic blood pressure in diabetic patients.

Effect of different dosages of dexamethasone therapy on lung function and inflammation in an early phase of acute respiratory distress syndrome model.

Inflammation associated with acute respiratory distress syndrome (ARDS) can damage the alveolar epithelium and surfactant and worsen the respiratory failure. Glucocorticoids (GC) appear to be a rational therapeutic approach, but the effect is still unclear, especially for early administration and low-dose. In this study we compared two low doses of dexamethasone in early phase of surfactant-depleted model of acute respiratory distress syndrome (ARDS). In the study, lung-lavaged New Zealand rabbits with respiratory failure (PaO(2)<26.7 kPa in FiO(2) 1.0) were treated with intravenous dexamethasone (DEX): 0.5 mg/kg (DEX-0.5) and 1.0 mg/kg (DEX-1.0), or were untreated (ARDS). Animals without ARDS served as controls. Respiratory parameters, lung edema, leukocyte shifts, markers of inflammation and oxidative damage in the plasma and lung were evaluated. Both doses of DEX improved the lung function vs. untreated animals. DEX-1.0 had faster onset with significant improvement in gas exchange and ventilation efficiency vs. DEX-0.5. DEX-1.0 showed a trend to reduce lung neutrophils, local oxidative damage, and levels of TNFalpha, IL-6, IL-8 more effectively than DEX-0.5 vs. ARDS group. Both dosages of dexamethasone significantly improved the lung function and suppressed inflammation in early phase ARDS, while some additional enhancement was observed for higher dose (1 mg/kg) of DEX.

The Association of Vitamin D Status with Acute Respiratory Morbidity in Preterm Infants.

OBJECTIVE: To assess the association between serum 25-hydroxyvitamin D (25OHD) levels and outcomes in preterm infants (<32 weeks gestation). STUDY DESIGN: Serum 25OHD was measured in mothers and their infants within 24 hours of birth, before the start of enteral vitamin D supplementation, and at discharge from the neonatal intensive care unit. We evaluated the associations between vitamin D status and various early preterm outcomes. RESULTS: Ninety-four preterm infants and their mothers were included; 92% of the infants had a 25OHD level≤50 nmol/L (20 ng/mL), and 64% had a 25OHD level<30 nmol/L (12 ng/mL). A low 25OHD level (<30 nmol/L) in preterm infants at birth was associated with increased oxygen requirement (P=.008), increased duration of intermittent positive-pressure ventilation during resuscitation at delivery (P=.032), and greater need for assisted ventilation (P=.013). CONCLUSION: We observed a high prevalence of low 25OHD (<30 nmol/L), and found an association between vitamin D status and acute respiratory morbidity in preterm infants after birth.

Nutritional immunomodulation in critically ill children with acute lung injury: feasibility and impact on circulating biomarkers.

OBJECTIVE: Respiratory failure caused by acute lung injury or acute respiratory distress syndrome is associated with significant morbidity in children. Enteral nutrition enriched with eicosapentaenoic acid, γ-linolenic acid and antioxidants (eicosapentaenoic acid + γ-linolenic acid) can safely modulate plasma phospholipid fatty acid profiles, reduce inflammation, and improve clinical outcomes in adults. There is little information regarding the use of enteral eicosapentaenoic acid + γ-linolenic acid to modulate plasma phospholipid fatty acid profiles in children. We sought to determine if continuous feeding of enteral nutrition containing eicosapentaenoic acid, γ-linolenic acid, and antioxidants was feasible in critically ill children with acute lung injury or acute respiratory distress syndrome. We further evaluated the impact of such an approach on the alteration of plasma phospholipid fatty acid concentrations. DESIGN: Prospective, blinded, randomized, controlled, multicenter trial. SETTING: PICU. PATIENTS: Twenty-six critically ill children (age 6.2 ± 0.9 yr, PaO2/FIO2 185 ± 15) with the diagnosis of acute lung injury or acute respiratory distress syndrome. INTERVENTIONS: Mechanically ventilated children received either eicosapentaenoic acid + γ-linolenic acid or a standard pediatric enteral formula. Clinical, biochemical, plasma fatty acid, and safety data were assessed at baseline, study days 4 and 7. MEASUREMENTS AND MAIN RESULTS: At baseline, there were no significant differences in the two study groups. Both groups met enteral feeding goals within 30 hrs and had similar caloric delivery. There were no differences in formula tolerance as measured by serum chemistries, liver and renal function, and hematology studies after 7 days of feeding either eicosapentaenoic acid + γ-linolenic acid or pediatric enteral formula. On study day 4 and 7, plasma phospholipid fatty acid profiles in the eicosapentaenoic acid + γ-linolenic acid group showed a significant increase in anti-inflammatory circulating markers. CONCLUSIONS: Providing enteral nutrition with eicosapentaenoic acid + γ-linolenic acid to critically ill children with lung injury was feasible and caloric goals were met within 30 hrs. This feeding protocol effectively modulated plasma phospholipid fatty acid concentrations to reflect an anti-inflammatory profile. This study provides data to inform future outcome studies using enteral eicosapentaenoic acid + γ-linolenic acid in children with lung injury.

Acute respiratory distress syndrome: evaluation and management.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition that affects patients admitted in the Intensive Care Units (ICUs) under mechanical ventilation. ARDS is a process of non-hydrostatic pulmonary edema and hypoxemia associated with a variety of conditions, resulting in a direct (e.g., pneumonia) or indirect (e.g., sepsis) lung injury and is associated with a significant morbidity and mortality. A large body of clinical and basic research has focused in ventilatory strategies and novel pharmacological therapies but, nowadays, treatment is mainly supportive. Mechanical ventilation is the hallmark of the management of these patients. In the last decades, the recognition that mechanical ventilation can contribute to harming the lung has changed the goals of this therapy and has driven research to focus in ventilatory strategies that mitigate lung injury. This review emphasizes clinical aspects in the evaluation and management of ARDS in the ICUs and updates the latest advances in these therapies.

Acute respiratory distress syndrome associated with hypercalcemia without parathyroid disorders.

Acute lung injury (ALI) can be induced by various causes. The occurrence of ALI associated with hypercalcemia has rarely been reported and the mechanisms are unknown. In the present study, we reported the clinical manifestation and pathological findings in patients with hypercalcemia and metastatic calcification. In addition, we addressed the possible mechanism and the preventive strategy for the acute episode of ALI due to hypercalcemic crisis. We encountered five patients with long-term malignancy of various origins. They displayed hypercalcemia and metastatic calcification in the kidney and stomach. One case with transitional cell carcinoma of the urinary bladder developed acute episode of acute respiratory distress syndrome (ARDS). The plasma calcium was elevated to above 5 mM. Simultaneously, He manifested ARDS followed by ALI. The pathological examination revealed severe alveolar edema with multiple calcification. In the other three cases, the plasma calcium level ranged from 3.1 to 4.4 mM and ARDS or ALI did not occur. One patient with esophageal squamous cell carcinoma experienced an acute hypercalcemia (plasma calcium 4.8-5.1 mM) accompanied by ARDS. Corticosteroid and calcitonin were prescribed to reduce the plasma calcium. The symptoms of ARDS also subsided and ALI did not occur. Chronic hypercalcemia results in severe metastatic calcification. The kidney and stomach are the most vulnerable organs. An increase in plasma calcium above 5 mM is a risk factor for developing ARDS and ALI. Our recent experiment in conscious rats and isolated rat's lungs supported this contention. In addition, corticosteroid and calcitonin were able to reduce the plasma calcium and to prevent the occurrence of ARDS and ALI.

Improvement by N-acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione, and extracellular thiol molecules and anti-oxidant power: evidence for underlying toxicological mechanisms.

In acute respiratory distress syndrome (ARDS), there is extensive overproduction of free radicals to the extent that endogenous anti-oxidants are overwhelmed, permitting oxidative cell damage. The present study examined the benefit of the anti-oxidant compound N-acetylcysteine (NAC) in the management of ARDS by measuring patient's intracellular glutathione (inside red blood cells) and extracellular (plasma) anti-oxidant defense biomarkers and outcome. Twenty-seven ARDS patients were recruited from the intensive care unit of a teaching Hospital and randomly divided into two groups. Both groups were managed similarly by regular treatments but 17 patients received NAC 150 mg/kg at the first day that followed by 50 mg/kg/day for three days and 10 patients did not receive NAC. Treatment by NAC increased extracellular total anti-oxidant power and total thiol molecules and also improved intracellular glutathione and the outcome of the patients. In conclusion, patients with ARDS are in a deficient oxidant-anti-oxidant balance that can get a significant benefit if supplemented with NAC.

[Effects of pulmonary arterial perfusion with shenqi fuzheng injection on lung injury during cardiopulmonary bypass].

OBJECTIVE: To observe the effect of pulmonary arterial perfusion with Shenqi Fuzheng Injection (SFI)on lung injury during cardiopulmonary bypass (CPB). METHODS: Twenty-two patients with cardiac valvular disease and pulmonary hypertension were randomly divided into the control and the SFI group equally. SFI mixed pure oxygenated blood to the SFI group, and oxygenated blood alone to the control group was perfused via pulmonary artery during CPB. Plasma malondialdehyde (MDA), pulmonary vascular resistance (PVR), ratio of leucocyte counts in venous and arterial blood, and time of mechanical ventilation applied were measured before and at the end of CPB, and 6th, 24th hours after CPB. RESULTS: After treatment, MDA content and PVR were significantly higher than those before CPB (P < 0.05), and reduced to normal level 24 h after CPB in both groups, but the peak levels were lower in the SFI group than those in the control group (P < 0.05). The leucocyte counts ratio in venous and arterial blood were significantly higher at the end of CPB and 6 h later than those before CPB in both groups (P < 0.05), but the increment were lower in the SFI group than those in the control group (P < 0.05). Furthermore, the applying mechanical ventilation time in the SFI group was 16.1 +/- 5.5 h, significantly shorter than that in the control group (29.1 +/- 6.9 h, P < 0.01). CONCLUSION: Pulmonary arterial perfusion with SFI could alleviate the CPB induced lung injury.

[Therapeutic effect of qingkailing and shengmai injection alone or combined on the acute lung injury induced by oleic acid in rabbits].

OBJECTIVE: To investigate the effect of Qingikailing and Shengmai injection alone or combined on the acute lung injury (AL) induced by oleic acid in rabbits. METHOD: The rabbits were randomly divided into 11 groups: oleic acid group; control group; treatment groups including low, middle and high dosage groups of Qingkailing and Shengmai injection alone and combined, respectively. ALI model was established by iv oleic acid (0.05 mL x kg(-1)) in these groups, and then iv above drugs respectively,while in control group, the same volume of normal saline was given. The respiratory amplitude and rate were observed, and blood samples were taken from cervical artery for blood-gas analysis before and at 30, 60, 120 min after oleic acid or normal saline administration. At the end of experiment, the concentration of LDH, CAT and MDA in the lung tissue were measured and pathologic changes of lung tissue were observed microscopically. RESULT: Compared with oleic acid group, the respiratory amplitude markedly enhanced (P < 0.05) in the low and high dose groups of Qingkailing and Shengmai injection. PaO2 increased significantly (P < 0.05) in the low dose group of combined Qingkailing and Shengmai injection, PaCO2 decreased markedly (P < 0.05) in the low dose groups of Qingkailing and Shengmai injection alone and combined. The level of MDA significantly decreased (P < 0.05) in the each group of Qingkailing and Shengmai injection alone, the level of MDA significantly decreased (P < 0.05) and CAT increased (P < 0.05) in the low dose group of combined Qingkailing with Shengmai injection. The low dose group of combined Qingkailing and Shengmai injection can alleviate the pathological changes induced by oleic acid. CONCLUSION: The curative effect of the low dose group of combined Qingkailing with Shengmai injection for the ALI induced by oleic acid was better than Qingkailing and Shengmai injection alone at the same dosage.

Treatment of ventilation-induced lung injury with exogenous surfactant.

OBJECTIVE: It has been demonstrated that pulmonary surfactant plays a role in the pathophysiology of ventilation-induced lung injury (VILI). Therefore, we investigated whether exogenous surfactant might restore lung function and lung mechanics in an established model of VILI. DESIGN: Prospective, randomized, animal study. SETTING: Experimental laboratory of a university. SUBJECTS: Twenty-four adult male Sprague-Dawley rats. INTERVENTIONS: First, a group of six animals were killed immediately after induction of anesthesia and used as healthy controls. Then, in 18 rats, VILI was induced by increasing peak inspiratory pressure (PIP) to 45 cmH2O without positive end-expiratory pressure (PEEP) for 20 min. Thereafter, animals were randomly divided into three groups of six animals each: one group was killed immediately after VILI and served as VILI-control. In the other two groups, ventilator settings were changed to a PIP of 30 cmH2O and a PEEP of 10 cmH2O, and a respiratory rate of 40 bpm. One group received a bolus of surfactant and the other group received no treatment. MEASUREMENTS AND RESULTS: Blood gas tension and arterial blood pressures were recorded every 30 min for 2 h. After the study period, a pressure-volume curve was recorded. Then, a broncho-alveolar lavage (BAL) was performed to determine protein content, minimal surface tension, and surfactant composition in the BAL fluid. Oxygenation, lung mechanics, surfactant function and composition were significantly improved in the surfactant-treated group compared to the ventilated and non-ventilated control groups. CONCLUSION: We conclude that exogenous surfactant can be used to treat VILI.

Low molecular weight dextran attenuates increase in extravascular lung water caused by ARDS.

We studied the effect of low molecular weight dextran (mean molecular weight 40,000, Dextran 40; LMD) on the accumulation of extravascular lung water (EVLW), and also on hemodynamics and blood gases, in the oleic acid (OA)-injured lung in pentobarbital anesthetized rats. Starting just before the OA injection (0.01 mL/kg via femoral vein), 10% LMD in lactated Ringer's solution was infused throughout the experiment (5 mL/kg/h) instead of lactated Ringer's solution. OA caused acute lung injury leading to decreased oxygenation (PaO2: 87 +/- 11 mmHg versus control group 128 +/- 11) and an increased permeability of the alveolar-capillary membrane, as shown by increases in EVLW (4.89 +/- 0.54 versus control group 4.07 +/- 0.14), and albumin leakage (0.043 +/- 0.015 versus control group 0.010 +/- 0.004). LMD protected against the increase in EVLW (4.14 +/- 0.10) and the hypoxemia (112 +/- 19 mmHg), but it did not reduce the albumin leakage into the alveolar space (0.052 +/- 0.009). These data suggest that LMD may limit the fluid accumulation that is secondary to OA-induced lung injury.

Partial liquid ventilation decreases serum tumor necrosis factor-alpha concentrations in a rat acid aspiration lung injury model.

OBJECTIVE: To examine the hypothesis that partial liquid ventilation (PLV) with perfluorocarbon would decrease serum tumor necrosis factor-alpha concentrations in a rat acid aspiration lung injury model. DESIGN: Prospective, controlled animal study. SETTINGS: Research laboratory in a university setting. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Treatment with intratracheal perflubron or control mechanical ventilation beginning 30 mins after acid aspiration. MEASUREMENTS AND MAIN RESULTS: PLV with perfluorocarbon compared with control ventilation resulted in significantly greater mean arterial blood pressures at 3 and 4 hrs and greater arterial Po2 at all times. Serum tumor necrosis factor-alpha at 2, 3, and 4 hrs was significantly less than that observed in the control group (4-hr values: 80+/-64 pg/mL vs. 658+/-688 pg/mL; p<.05), although no significant difference in tracheal fluid tumor necrosis factor-alpha concentrations (1425+/-1347 pg/mL vs. 2219+/-1933 pg/mL) was found. CONCLUSION: We conclude that the effects of PLV with perfluorocarbon can extend beyond improvements in pulmonary physiology and that PLV may be beneficial in reducing systemic sequelae of acute lung injury and inflammation.

Lidocaine attenuates acute lung injury induced by a combination of phospholipase A2 and trypsin.

OBJECTIVE: Acute severe pancreatitis is often associated with acute lung injury, including acute respiratory distress syndrome. Acute lung injury induced by phospholipase A2 (PLA2) or trypsin, a pancreatic enzyme, is an experimental model resembling acute respiratory distress syndrome. Neutrophils and platelets are thought to play a pivotal role in the pathogenesis of acute respiratory failure. Lidocaine inhibits some aspects of neutrophil and platelet functions. We conducted the current study to assess the effects of pretreatment with lidocaine on acute lung injury induced by a combination of PLA2 and trypsin. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Twenty-one adult male Japanese White rabbits (weight range, 2.0-2.4 kg). INTERVENTIONS: The animals were mechanically ventilated with a tidal volume of 10 mL/kg and an Fio2 of 0.4, and thereafter, they were randomly assigned to three groups. Acute lung injury was induced by a combination of PLA2 (1000 units/kg/hr) and trypsin (5000 units/kg/hr) infused intravenously for 4 hrs. Immediately before induction of the acute lung injury, the lidocaine treatment group received intravenous lidocaine (2 mg/kg bolus followed by 2 mg/kg/hr) until they were killed. In the nontreatment group, saline was given instead of lidocaine. Rabbits in the nonlung-injury group received saline infusion instead of the pancreatic enzymes. MEASUREMENTS AND MAIN RESULTS: During the experimental period (4 hrs), arterial blood gases, lung mechanics, and peripheral neutrophil and platelet counts were measured. Immediately after killing, the wet weight/dry weight ratio of the lung was recorded. Light microscopic findings (lung injury score and number of neutrophils) were compared between the three groups. The combination of PLA2 and trypsin decreased Pao2, lung compliance, and peripheral counts of neutrophils and platelets and increased alveolar/arterial oxygen tension difference, lung resistance, wet weight/dry weight ratio, and the number of neutrophils in the lung. Lidocaine treatment attenuated these changes. The two pancreatic enzymes caused extensive morphologic lung damage, which was lessened by lidocaine. CONCLUSIONS: We conclude that pretreatment with intravenous lidocaine attenuated the lung injury induced by the pancreatic enzymes. However, further studies are required to determine whether this drug has a therapeutic effect once the lung injury has developed.

[Changes of the deformability of neutrophil and the influence of anisodamine on neutrophil deformability during endotoxin-induced acute lung injury in rats].

OBJECTIVE: To explore the mechanisms of change of deformability of polymorphonuclear leukocytes (PMN) and influence of anisodamine on deformability of PMN during endotoxin-induced acute lung injury (ALI) in rat. To explore the role of PMN in ALI. METHOD: The model of ALI in rat was reproduced by intravenous injection of E Coli endotoxin. The deformability of PMN was measured by micropipette aspiration technique. RESULT: The elastic modulus K1 of PMN at the 1st hour (33 +/- 12 Pa), 4th hours (37 +/- 12 Pa, 1 Pa = 0.0075 mmHg) and 6th hours (38 +/- 13 Pa) after injection of E Coli endotoxin are all significantly higher than that in the control group (26 +/- 9 Pa P < 0.01). The viscosity modulus (mu) of PMN at the 4th hours (5 +/- 3 Pa.s) and 6th hours (6 +/- 3 Pa.s) after injection of E Coli endotoxin are all significantly higher than the control group (3.1 +/- 2.6 Pa.s, P < 0.01). The elastic shear modulus (G) of PMN at the 4th hours (54 +/- 20 Pa) and the 6th hours (56 +/- 21 Pa) after injection of E Coli endotoxin are all significantly higher than the control group (47 +/- 17 Pa, P < 0.05). The K1(33 +/- 12 Pa) and mu(4 +/- 3 Pa.s) in anisodamine group are all significantly lower than endotoxin group in the same time phases (P < 0.05). CONCLUSION: The deformability of PMN decrease remarkably during ALI, which will enhance PMN sequestration in lungs, lead to ALI. It may be one of important pathogenic mechanism of ALI. The anisodamine can inhibit the decrease of deformability of PMN effectively and may have some therapeutic effect on ALI.

N-acetylcysteine pretreatment of cardiac surgery patients influences plasma neutrophil elastase and neutrophil influx in bronchoalveolar lavage fluid.

OBJECTIVE: Study of leukocyte activation and release of toxic mediators during extracorporeal circulation (ECC). ECC can be used to study the potential protective effect of a pharmacon against neutrophil-mediated lung injury. Clinical studies have indicated that N-acetylcysteine (NAC) may improve systemic oxygenation and reduce the need for ventilatory support when given to patients with acute lung injury. DESIGN: Cardiac surgery patients were pretreated with high-dose NAC in order to assess the potential role of NAC to interfere with neutrophil-mediated inflammation and lung injury. PATIENTS: 18 patients who underwent ECC: group 1 (n = 8) no premedication (only placebo); group 2 (n = 10) NAC (72 mg/kg i.v. as a bolus, later 72 mg/kg over 12 h). MEASUREMENTS AND RESULTS: In group 2, the partial pressure of oxygen in arterial blood/fractional inspired oxygen 4 h after surgery was significantly higher than in group 1 (213 +/- 31 vs 123 +/- 22; p = 0.044). NAC pretreatment prevented an increase in plasma neutrophil elastase activity (18.9 +/- 6.9 vs 49.9 +/- 5.6 ng/ml in group 1 at the end of ECC; p = 0.027). Release of myeloperoxidase (MPO) was not affected (group 1:1105 +/- 225 ng/ml vs group 2:1127 +/- 81 at the end of ECC; p = 0.63). At the end of ECC, total antigenic human neutrophil elastase (group 1:671 +/- 72 ng/ml vs group 2:579 +/- 134; p = 0.37) and complex formation between elastase and alpha 1-proteinase inhibitor were no different in the two groups. There were no significant difference in cellular composition and mediators in the lavage fluid, although values for total number of neutrophils, elastase, MPO and interleukin-8 were lower in group 2. CONCLUSION: Pretreatment with NAC may prevent lung injury by diminishing elastase activity. Since the release of mediators, especially MPO, is not affected, this diminished activity of elastase may be achieved by enhanced inactivation by antiproteases after initial treatment.

Partial liquid ventilation provides effective gas exchange in a large animal model.

PURPOSE: The purpose of this study was to show the ability of partial liquid ventilation (PLV) to sustain gas exchange in normal large (50 to 70 kg) adult animals. METHODS: Ten adult sheep (53.7 +/- 2.8 kg) were anesthetized and mechanically ventilated. Sequential dosing of perflubron (LiquiVent, Alliance Pharmaceutical Corp, San Diego, CA) was performed to cumulative doses of 10 mL/kg, 20 mL/kg, 40 mL/kg, and 60 mL/kg. Physiological data were assessed at baseline and after each dose. Five animals were rotated through the left decubitus, right decubitus, supine, and prone positions while five animals remained prone throughout the experiment. RESULTS: PaO2 and PaCO2 did not change significantly from baseline during administration of perflubron except for the PaO2 in rotated animals when supine (rotated-supine PaO2: baseline = 519 +/- 64 mm Hg; 60 mL/kg = 380 +/- 109 mm Hg, P = .0131). In both groups, static lung compliance (CT) decreased steadily with each successive perflubron instillation (nonrotated CT: baseline = 1.55 +/- 0.22 mL/cm H2O/kg; 60 mL/kg = 0.52 +/- 0.10 ml/cmH2O/kg, P = .0003). CONCLUSIONS: These data show that during PLV in this normal animal model, effective gas exchange is sustained and CT decreases with increasing perflubron dose.

A novel leukotriene B4-receptor antagonist in endotoxin shock: a prospective, controlled trial in a porcine model.

OBJECTIVE: To evaluate the hypothesis that treatment with LY255283, a novel leukotriene B4-receptor antagonist, is beneficial in an animal model of the adult respiratory distress syndrome induced by endotoxin. DESIGN: Prospective, randomized, controlled trial. SETTING: Laboratory at a large university medical center. SUBJECTS: Twenty-five, immature, random-bred swine. INTERVENTIONS: Four groups of pigs were studied: the LPS group of animals (n = 6) were infused with Escherichia coli lipopolysaccharide (strain 0111:B4, 250 micrograms/kg) from 0 to 60 mins; the LPS + 255283 group of animals (n = 6) were infused with lipopolysaccharide as above, but were also treated with LY255283 (30 mg/kg, then 10 mg/kg/hr), beginning at -15 mins; the 255283 group of animals (n = 6) were infused with the same dose of LY255283, but were not challenged with lipopolysaccharide; and the RL control group of subjects (n = 7) received only the lactated Ringer's solution vehicle. Beginning at 30 mins, all groups were infused with dextran-70 solution as needed to maintain cardiac output at 90% to 110% of baseline value. MEASUREMENTS AND MAIN RESULTS: Treatment with LY255283 significantly (p < .05) ameliorated lipopolysaccharide-induced systemic arterial hypotension, pulmonary arterial hypertension, and arterial hypoxemia. Treatment with this drug also abrogated lipopolysaccharide-induced increases in pulmonary extravascular water content and bronchoalveolar lavage fluid protein concentration. CONCLUSIONS: These data suggest that leukotriene B4 may be an important mediator of acute lung injury in this porcine model of septic shock and acute lung injury. Further studies to assess the specificity of LY255283 as a leukotriene B4 antagonist are necessary in order to exclude the possibility that the beneficial effects of this compound are due to pharmacologic actions other than the blockade of LTB4 receptors.

Inhaled nitric oxide in the adult respiratory distress syndrome and other lung diseases.

In 1987, nitric oxide was reported to be an endothelium-dependent relaxing factor. When inhaled as a gas at low levels, nitric oxide selectively dilates the pulmonary circulation. Significant systemic vasodilation does not occur because nitric oxide is inactivated by rapidly binding to hemoglobin. In an injured lung with pulmonary hypertension, inhaled nitric oxide produces local vasodilation of well-ventilated lung units and may "steal" blood flow away from unventilated regions. This reduces intrapulmonary shunting and may improve systemic arterial oxygenation. In patients with adult respiratory distress syndrome, inhaled nitric oxide reduces pulmonary hypertension and improves arterial oxygenation without reducing systemic arterial pressure. Tachyphylaxis to nitric oxide inhalation has not been observed. While additional chronic toxicology studies need to be performed, significant pulmonary toxicity has not been observed at low inhaled concentrations (< 80 parts per million by volume). Potentially, inhaled nitric oxide may be a valuable therapy in patients with adult respiratory distress syndrome.

[Effect of hyperbaric oxygenation on the corticosterone content of the blood in experimental acute respiratory distress syndrome]. / Vliianie giperbaricheskoi oksigenatsii na soderzhanie kortikosterone v krovi pri ostrom respiratornom distress-sindrome v éksperimente.

The three series of experiments conducted on 139 adult wistar rats it was found, that two-hour stay of the animals in barochamber under the pressure of 3 atmospheres reduces considerably the percentage of mortality rate and decelerates the development of arterial hypoxemia in rats with an experimental model of acute respiratory distress syndrome (ARDS) reproduced by intrapleural injection of oleic acid (0.27 ml/100 g). Stalle in comparison with the control (I) series elevation of corticosterone in the animal blood II and III series (conduction of HBO correspondingly in 4 and 12 hours from the beginning of the process) is considered as the manifestation of one of the most important mechanism of organism adaptation to the development of acute hypoxia in ARDS.

A critical comparison of the hematologic, cardiovascular, and pulmonary response to steroids and nonsteroidal anti-inflammatory drugs in a model of sepsis and adult respiratory distress syndrome.

Improved survival of patients receiving high-dose steroid therapy in sepsis and adult respiratory distress syndrome (ARDS) has been reported, but such therapy and its benefits remain controversial. Recently research has been directed toward manipulation of the arachidonic acid cascade. Improved survival and hemodynamics with administration of nonsteroidal anti-inflammatory drugs (NSAID) have been reported in animal models of sepsis and ARDS. The purpose of this study was to compare the effects of steroids (methylprednisolone) and NSAID (ibuprofen) in a porcine model of septic ARDS induced by a continuous infusion of live Pseudomonas aeruginosa. Cardiopulmonary parameters were monitored in animals intubated, paralyzed, and ventilated at a 250 ml tidal volume and 0.5 Fio2. Pigs were randomly assigned to one of five groups: groups I and II received respective doses of 12.5 mg/kg ibuprofen and 30 mg/kg methylprednisolone at 20 and 210 minutes after baseline; group III had P. aeruginosa only; groups IV and V received respective doses of ibuprofen and methylprednisolone at 20 and 210 minutes of sepsis. Significant pulmonary edema, increased intrapulmonary shunting, hypoxemia, hemoconcentration, and systemic hypotension occurred with P. aeruginosa infusion. In septic animals treated with ibuprofen normal systemic arterial pressure was maintained, hemoconcentration was decreased, and oxygenation was improved with a significant decrease in shunting and pulmonary edema. Administration of methylprednisolone improved hemoconcentration and cardiac index, but no significant effect on pulmonary edema, intrapulmonary shunting, or oxygenation was observed. The results of this study demonstrated a significant beneficial effect of ibuprofen and we would encourage controlled clinical trials of this drug in the management of sepsis and ARDS. On the other hand, methylprednisolone was found to be relatively ineffective in treatment of circulatory collapse and ARDS associated with sepsis.