Partial liquid ventilation reduces pulmonary neutrophil accumulation in an experimental model of systemic endotoxemia and acute lung injury

OBJECTIVE: To determine whether pulmonary neutrophil sequestration and lung injury are affected by partial liquid ventilation with perfluorocarbon in a model of acute lung injury (ALI). DESIGN: A prospective, controlled, in vivo animal laboratory study. SETTING: An animal research facility of a health sciences university. SUBJECTS: Forty-one New Zealand White rabbits. INTERVENTIONS: Mature New Zealand White rabbits were anesthetized and instrumented with a tracheostomy and vascular catheters. Animals were assigned to receive partial liquid ventilation (PLV, n = 15) with perflubron (18 mL/kg via endotracheal tube), conventional mechanical ventilation (CMV, n = 15) or high-frequency oscillatory ventilation (HFOV, n = 5). Animals were ventilated, using an FIO2 of 1.0, and ventilatory settings were required to achieve a normal PaCO2. Animals were then given 0.9 mg/kg of Escherichia coli endotoxin intravenously over 30 mins. Partial liquid ventilation, conventional mechanical ventilation, or high-frequency oscillatory ventilation was continued for an additional 4 hrs before the animals were killed. A group of animals not challenged with endotoxin underwent conventional ventilation for 4.5 hrs, serving as the control group (control, n = 6). Lungs were removed and samples were frozen at -70 degrees C. Representative samples were stained for histology. A visual count of neutrophils per high-power field (hpf) was performed in five randomly selected fields per sample in a blinded fashion by light microscopy. Lung samples were homogenized in triplicate in phosphate buffer, ultrasonified, freeze-thawed, and clarified by centrifugation. Supernatants were analyzed for myeloperoxidase (MPO) activity by spectrophotometry with o-dianisidine dihydrochloride and hydrogen peroxide at 460 nm. MEASUREMENTS AND MAIN RESULTS: Histologic analysis of lung tissue obtained from control animals showed normal lung architecture. Specimens from the PLV and HFOV groups showed a marked decrease in alveolar proteinaceous fluid, pulmonary vascular congestion, edema, necrotic cell debris, and gross inflammatory infiltration when compared with the CMV group. Light microscopy of lung samples of animals supported with PLV and HFOV had significantly lower neutrophil counts when compared with CMV (PLV, 4 +/- 0.3 neutrophils/hpf; HFOV, 4 +/- 0.5 neutrophils/hpf; CMV, 10 +/- 0.9 neutrophils/hpf; p < .01). In addition, MPO activity from lung extracts of PLV and HFOV animals was significantly lower than that of CMV animals (PLV, 61 +/- 13.3 units of MPO activity/lung/kg; HFOV, 43.3 +/- 6.8 units of MPO activity/lung/kg; CMV, 140 +/- 28.5 units of MPO activity/lung/kg; p < .01). MPO activity from lungs of uninjured control animals was significantly lower than that of animals in the PLV, HFOV, and CMV groups (control, 2.2 +/- 2 units of MPO activity/lung/kg; p < .001). CONCLUSIONS: Partial liquid ventilation decreases pulmonary neutrophil accumulation, as shown by decreased neutrophil counts and MPO activity, in an experimental animal model of ALI induced by systemic endotoxemia. The attenuation in pulmonary leukostasis in animals treated with PLV is equivalent to that obtained by a ventilation strategy that targets lung recruitment, such as HFOV.     

Effects of partial liquid ventilation on lung injury in a model of acute respiratory failure: a histologic and morphometric analysis

OBJECTIVE: To compare the histopathologic changes observed in a sheep model of oleic acid-induced acute respiratory failure during partial liquid ventilation with perflubron with gas ventilation. DESIGN: Randomized, controlled study. SETTING: Animal laboratory and pathology laboratories of a university hospital. SUBJECTS: Fourteen healthy adult sheep, weighing 64.9 +/- 6.4 kg. INTERVENTIONS: Lung injury was induced with oleic acid (0.15 mL/kg). A tracheostomy tube was inserted, along with systemic and pulmonary artery monitoring catheters. Animals were randomized to undergo either partial liquid ventilation (n = 7) or gas ventilation (n = 7). Animals underwent euthanasia at the end of the 90-min study period, after which the endotracheal tube was clamped with the lungs in expiratory hold at a positive end-expiratory pressure of 5 cm H2O. En bloc excision of the heart and lungs was performed by thoracotomy. Perfusion of the isolated lung vasculature with 2.5% paraformaldehyde and 0.25% glutaraldehyde in a 0.1-M phosphate buffer was performed. Histologic analysis followed. MEASUREMENTS AND MAIN RESULTS: Gas exchange increased markedly in the animals that underwent partial liquid ventilation compared with the gas-ventilated animals (PaO2 at 90 mins: gas ventilation-treatment group, 40 +/- 8 torr [5.3 +/- 1.1 kPa]; partial liquid ventilation-treatment group, 108 +/- 60 torr [14.4 +/- 8.0 kPa]; p = .004). Lung histologic analysis demonstrated a better overall diffuse alveolar damage score (partial liquid ventilation-treatment group, 12.4 +/- 1.4; gas ventilation-treatment group, 15.0 +/- 1.7; p = .01). In the partial liquid ventilation-treatment group, we observed an increase in mean alveolar diameter (partial liquid ventilation-treatment group, 82.4 +/- 2.9 microm; gas ventilation-treatment group, 67.7 x 3.9 microm; p = .0022) and a decrease in the number of alveoli per high-power field (partial liquid ventilation-treatment group, 25.7 +/- 0.9, gas ventilation-treatment group, 31.4 +/- 2.5; p = .0022), in septal wall thickness (partial liquid ventilation-treatment group, 6.0 +/- 0.6 microm; gas ventilation-treatment group, 8.3 +/- 1.0 microm; p = .0033), and in mean capillary diameter (partial liquid ventilation-treatment group, 13.0 +/- 0.8 microm; gas ventilation-treatment group, 19.9 +/- 1.4 microm; p = .0022). CONCLUSIONS: Partial liquid ventilation is associated with notable improvement in gas exchange and with a reduction in the histologic and morphologic changes observed in an oleic acid model of acute lung injury.     

Effect of Ca-antagonists on pulmonary blood flow during single-lung ventilation in the dog

Experiments were conducted in 21 adult mongrel dogs to clarify the effects of Ca-antagonist (nifedipine sublingual administration 2.5 mg or 5 mg, or nicardipine intravenous administration 30 micrograms/kg or 60 micrograms/kg) on pulmonary blood flow under the condition of collapsed lung on the side of thoracotomy. Under anesthesia, an endotracheal tube with a movable blocker was used to intubate the trachea and the thoracotomized lung was collapsed. Subsequently, a Ca-antagonist was given and the ratio of the left main pulmonary artery/ascending thoracic aorta blood flow was used as an index of hypoxic pulmonary vasoconstriction (HPV). The following results were obtained. 1. Ca-antagonist administration under lung-collapse on the thoracotomy side resulted in inhibition of HPV of the collapsed lung, whereas, arterial blood oxygen tension (PaO2) remained in the acceptable range. 2. The maintenance of the lowered PaO2 within the acceptable range may have been due to the increase in cardiac output and the elevation of mixed venous blood oxygen tension resulting from Ca-antagonist administration, as well as the residual HPV even after administration of the Ca-antagonist.     

Neutrophil accumulation is reduced during partial liquid ventilation

OBJECTIVE: This study evaluates the ability of perflubron to inhibit pulmonary neutrophil accumulation during partial liquid ventilation (PLV) in the setting of acute lung injury. DESIGN: Randomized, controlled, nonblinded study. SETTING: Research laboratory at a university. SUBJECTS: Male, Sprague-Dawley rats (n = 120, 506 +/- 42 g). INTERVENTIONS: Animals were divided into eight groups (n = 15 in each group, of which n = 12 for myeloperoxidase content and n = 3 for histologic neutrophil counting): a) GV-CVF group, animals received gas ventilation (GV) with the induction of lung injury using cobra venom factor (CVF); b) PLV-CVF group, animals received partial liquid ventilation before the induction of lung injury; c) PEEP-CVF group, animals received positive end-expiratory pressure (PEEP) before the administration of cobra venom factor; d) CVF-PLV group, animals received partial liquid ventilation after cobra venom factor; e) CVF-PEEP group, animals received PEEP after cobra venom factor; f) PLV only group, animals received partial liquid ventilation only; g) GV only group, animals received gas ventilation only; and h) NVSBA group, nonventilated spontaneous breathing animals. MEASUREMENTS AND MAIN RESULTS: After the experimental period, total lung myeloperoxidase content was significantly decreased in the PLV-CVF (0.29 +/- 0.08, p = .02) and PEEP-CVF (0.34 +/- 0.04, p = .01) groups when compared with the GV-CVF group (0.62 +/- 0.07). When compared with the GV-CVF group, a trend toward a reduction in myeloperoxidase was observed in the CVF-PLV (0.42 +/- 0.05, p = .07) and the CVF-PEEP (0.39 +/- 0.06, p = .07) groups. When compared with the cobra venom factor only group (GV-CVF 47 +/- 2 neutrophils/high-power field), reductions in neutrophil count were observed in all groups (neutrophils/high-power field): PLV-CVF (20 +/- 2, p = .009); PEEP-CVF (24 +/- 1, p = .01); CVF-PLV (30 +/- 2, p = .03); and CVF-PEEP (37 +/- 1, p = .04). CONCLUSION: These data suggest that both partial liquid ventilation and PEEP result in a reduction in neutrophil accumulation in the setting of acute lung injury.     

Mechanical ventilation of patients with acute lung injury

Ventilatory management of patients with acute lung injury (ALI), particularly its most severe subset, acute respiratory distress syndrome (ARDS), is complex. Newer lung protective strategies emphasize measures to enhance alveolar recruitment and avoid alveolar overdistention, thus minimizing the risk of ventilator-induced lung injury (VILI). Key components of such strategies include the use of smaller-than-conventional tidal volumes which maintain peak transpulmonary pressure below the pressure associated with overdistention, and titration of positive end-expiratory pressure to promote maximal alveolar recruitment. Novel techniques, including prone positioning, inverse ratio ventilation, tracheal gas insufflation, and high frequency ventilation, are considerations in severe ARDS. No single approach is best for all patients; adjustment of ventilatory parameters to individual characteristics, such as lung mechanics and gas exchange, is required.     

Response to inhaled nitric oxide in acute lung injury depends on distribution of pulmonary blood flow prior to its administration

Responses to inhaled nitric oxide (iNO) in acute lung injury (ALI), as evidenced by improvements in oxygenation, are variable. We hypothesized that the effect of iNO may be related to the pre-iNO distribution of pulmonary blood flow (PBF). In the present study we evaluated the effect of iNO on PBF in normal healthy dogs and in a canine model of ALI induced by oleic acid (OA). In Group "OA only" (n = 5), ALI was induced by central venous injection of 0.08 ml/kg OA. In Group "E+OA" (n = 5), hypoxic pulmonary vasoconstriction after ALI was blocked with low-dose endotoxin (15 microg/kg of Escherichia coli endotoxin) administered 30 min before giving the same dose of OA. Measurements of regional PBF and lung water concentration (LWC) using positron emission tomography (PET) and H215O were performed before and after OA or placebo, and then again at concentrations of 10, 40, and 0 ppm iNO. One hundred twenty minutes after OA injury, PaO2/FIO2 fell significantly in Group OA only, from 567 +/- 32 to 437 +/- 67 mm Hg. In these animals, PBF redistributed from the dorsal edematous regions of the lungs to the nondependent zones, thus partially preserving normal ventilation/ perfusion relationships. As in the normal animals, in Group OA only, iNO did not significantly change either PBF or oxygenation. In Group E+OA, the administration of low-dose endotoxin eliminated perfusion redistribution from the dorsal edematous lung regions. As a result, PaO2/FIO2 fell from 558 +/- 70 to 119 +/- 53 mm Hg, a decrease that was significantly greater than that in Group OA only. In Group E+OA, administration of iNO restored perfusion redistribution to a similar level as in Group OA only, which was associated with a significant improvement in PaO2/FIO2, from 119 +/- 53 to 251 +/- 159 (10 ppm iNO), and 259 +/- 165 mm Hg (40 ppm iNO). We conclude that the effect of iNO on oxygenation after ALI depends on the pre-iNO perfusion pattern, which may help explain the variable response to iNO often observed in patients with acute respiratory distress syndrome.     

Continuous low-flow tracheal gas insufflation during partial liquid ventilation in rabbits

BACKGROUND: Both partial liquid ventilation (PLV) and tracheal gas insufflation are novel techniques for mechanical ventilation. In this study we examined whether PLV superimposed by continuous low-flow tracheal gas insufflation (TGI) offers any advantage to the blood gases and lung mechanics in normal-lung rabbits compared to the use of PLV only. METHODS: Eighteen anesthetized, paralyzed and mechanically ventilated rabbits were used. After obtaining a baseline PaCO2 value between 29 and 39 mmHg (3.9 and 5.2 kPa), the animals were assigned to three equal groups according to the ventilation they received--A group: PLV superimposed by TGI; B group: PLV only; and C group: continuous mandatory ventilation (CMV) superimposed by TGI. Serial arterial blood gases, pH and lung mechanics were measured. RESULTS: The animals in each group were hemodynamically stable. In the case of the A group, PaO2 continuously increased, and PaCO2 stabilized around 40.8 +/- 5.5 mmHg (5.4 +/- 0.7 kPa, mean +/- SD, NS). In the B group, the tendency for PaO2 to increase was not as definite; PaCO2 continuously increased from 35.2 +/- 2.3 mmHg (4.7 +/- 0.3 kPa) to 56.3 +/- 12.7 mmHg (7.5 +/- 1.7 kPa, P < 0.05) at the end of the experiment. In the C group, PaO2 and PaCO2 were stable during the observation period. The superimposition of TGI on PLV did not decrease the airway pressures compared to PLV alone. CONCLUSION: In summary, continuous low-flow TGI superimposed on PLV can decrease and stabilize the PaCO2 elevation caused by the initiation of PLV.     

Partial liquid ventilation protects lung during resuscitation from shock

Preliminary animal experience with partial liquid ventilation (PLV) suggests that this therapy may diminish neutrophil invasion and capillary leak during acute lung injury. We sought to confirm these findings in a model of shock-induced lung injury. Sixty anesthetized rats were studied. After hemorrhage to an arterial pressure of 25 mmHg for 45 min, animals were resuscitated with blood and saline and treated with gas ventilation alone or with 5 ml/kg of intratracheally administered perflubron. Myeloperoxidase activity was used to measure lung neutrophil content. A permeability index (the bronchoalveolar-to-blood ratio of 125I-labeled albumin activity) quantified alveolar leak. Injury caused an increase in myeloperoxidase that was reversed by PLV (injury = 0.837 +/- 0.452, PLV = 0.257 +/- 0.165; P < 0.01). Capillary permeability also increased with hemorrhage, with a strong trend toward improvement in the PLV group (permeability indexes: injury = 0.094 +/- 0.102, PLV = 0.045 +/- 0.045; 95% confidence interval for injury--PLV: -0.024, 0.1219). We conclude that PLV is associated with a decrease in pulmonary neutrophil accumulation and a trend toward decreased capillary leak after hemorrhagic shock.     

Does airway pressure release ventilation alter lung function after acute lung injury?

BACKGROUND: During airway pressure release ventilation (APRV), tidal ventilation occurs between the increased lung volume established by the application of continuous positive airway pressure (CPAP) and the relaxation volume of the respiratory system. Concern has been expressed that release of CPAP may cause unstable alveoli to collapse and not reinflate when airway pressure is restored. OBJECTIVE: To compare pulmonary mechanics and oxygenation in animals with acute lung injury during CPAP with and without APRV. DESIGN: Experimental, subject-controlled, randomized crossover investigation. SETTING: Anesthesiology research laboratory, University of South Florida College of Medicine Health Sciences Center. SUBJECTS: Ten pigs of either sex. INTERVENTIONS: Acute lung injury was induced with an intravenous infusion of oleic acid (72 micrograms/kg) followed by randomly alternated 60-min trials of CPAP with and without APRV. Continuous positive airway pressure was titrated to produce an arterial oxyhemoglobin saturation of at least 95% (FIO2 = 0.21). Airway pressure release ventilation was arbitrarily cycled to atmospheric pressure 10 times per minute with a release time titrated to coincide with attainment of respiratory system relaxation volume. MEASUREMENTS: Cardiac output, arterial and mixed venous pH, blood gas tensions, hemoglobin concentration and oxyhemoglobin saturation, central venous pressure, pulmonary and systemic artery pressures, pulmonary artery occlusion pressure, airway gas flow, airway pressure, and pleural pressure were measured. Tidal volume (VT), dynamic lung compliance, intrapulmonary venous admixture, pulmonary vascular resistance, systemic vascular resistance, oxygen delivery, oxygen consumption, and oxygen extraction ratio were calculated. MAIN RESULTS: Central venous infusion of oleic acid reduced PaO2 from 94 +/- 4 mm Hg to 52 +/- 9 mm Hg (mean +/- 1 SD) (p < 0.001) and dynamic lung compliance from 40 +/- 6 mL/cm H2O to 20 +/- 6 mL/cm H2O (p = 0.002) and increased venous admixture from 13 +/- 3% to 32 +/- 7% (p < 0.001) in ten swine weighing 33.3 +/- 4.1 kg while they were spontaneously breathing room air. After induction of lung injury, the swine received CPAP (14.7 +/- 3.3 cm H2O) with or without APRV at 10 breaths per minute with a release time of 1.1 +/- 0.2 s. Although mean transpulmonary pressure was significantly greater during CPAP (11.7 +/- 3.3 cm H2O) vs APRV (9.4 +/- 3.8 cm H2O) (p < 0.001), there were no differences in hemodynamic variables. PaCO2 was decreased and pHa was increased during APRV vs CPAP (p = 0.003 and p = 0.005). PaO2 declined from 83 +/- 4 mm Hg to 79 +/- 4 mm Hg (p = 0.004) during APRV, but arterial oxyhemoglobin saturation (96.6 +/- 1.4% vs 96.9 +/- 1.3%) did not. Intrapulmonary venous admixture (9 +/- 3% vs 11 +/- 5%) and oxygen delivery (469 +/- 67 mL/min vs 479 +/- 66 mL/min) were not altered. After treatment periods and removal of CPAP for 60 min, PaO2 and intrapulmonary venous admixture returned to baseline values. DISCUSSION: Intrapulmonary venous admixture, arterial oxyhemoglobin saturation, and oxygen delivery were maintained by APRV at levels induced by CPAP despite the presence of unstable alveoli. Decrease in PaO2 was caused by increase in pHa and decrease in PaCO2, not by deterioration of pulmonary function. We conclude that periodic decrease of airway pressure created by APRV does not cause significant deterioration in oxygenation or lung mechanics.     

PEEP and low tidal volume ventilation reduce lung water in porcine pulmonary edema

Gonococci producing a distinct opacity protein (OpaA in strain MS11) adhere to and are efficiently internalized by cultured epithelial cells such as the Chang conjunctiva cell line. Both adherence and uptake require interactions between OpaA and heparan sulfate proteoglycans on the mammalian cell surface. Chinese hamster ovary (CHO) cells also support adherence of gonococci through interactions of OpaA with cell surface heparan sulfate proteoglycans. However, despite this similarity in the requirements for adherence, CHO cells are not capable of internalizing gonococci. In this report, we characterized this apparent deficiency and identified a factor in fetal calf serum (FCS) which is capable of mediating uptake of gonococci by CHO cells. In the absence of FCS, OpaA+ gonococci adhered to but were not internalized by CHO cells, whereas in the presence of up to 15% FCS, the bacteria were efficiently internalized by the cells. Preincubation of bacteria, but not cells, with FCS also stimulated internalization, suggesting that a factor present in FCS was binding to the surface of gonococci and subsequently stimulating entry. Using a combination of chromatographic purification procedures, we identified the adhesive glycoprotein vitronectin as the serum factor which mediates the internalization of gonococci by CHO cells. Vitronectin-depleted serum did not support gonococcal entry, and this deficiency was restored by the addition of purified vitronectin. Further experiments using a set of gonococcal recombinants, each expressing a single member of the family of Opa outer membrane proteins, demonstrated that vitronectin bound to the surface of OpaA-producing gonococci only and that the vitronectin-mediated uptake by the CHO cells was limited to this bacterial phenotype. To our knowledge, our data are the first example that vitronectin can serve as a molecule that drives bacterial entry into epithelial cells.     

Surfactant replacement increases compliance in premature lamb lungs during partial liquid ventilation in situ

Treatments available to improve compliance in surfactant-deficient states include exogenous surfactant (ES) and either partial (PLV) or total liquid ventilation (TLV) with perfluorochemical (PFC). Because of the additional air-lung and air-PFC interfaces introduced during PLV compared with TLV, we hypothesized that compliance would be worse during PLV than during TLV. Because surfactant is able to reduce interfacial tension between air and lung as well as between PFC and lung, we further hypothesized that compliance would improve with surfactant treatment before PLV. In excised preterm lamb lungs, we used Survanta for surfactant replacement and perflubron as the PFC. Compliance during PLV was intermediate between TLV and gas inflation, both with and without surfactant. Surfactant improved compliance during PLV, compared with PLV alone. Because of the force-balance equation governing the behavior of immiscible droplets on liquid surfaces, we predict that PFC droplets spread during PLV to cover the alveolar surface in surfactant-deficient lungs during most of lung inflation and deflation but that the PFC would retract into droplets in surfactant-sufficient lungs, except at end inspiration.     

High-frequency jet ventilation during the treatment of acute fulminant pulmonary edema

High-frequency jet ventilation (HFJV) was used during the treatment of fulminant pulmonary edema in a 45-year-old man so that toxic levels of oxygen could be avoided when conventional methods of ventilation in combination with high levels of PEEP (20 cm H2O) were unsuccessful in raising PaO2. On each of four occasions, HFJV resulted in improved arterial oxygenation when compared with conventional modes.     

Pulmonary pathology of patients treated with partial liquid ventilation

Adsorption and size exclusion in starch and cross-linked dextran were phenomena discovered in Uppsala in the 1950s [Porath (1979), Biochem. Soc. Trans. 7, 1197; Porath (1981), Current Content 19, 21; Porath (1981), J. Chromatogr. 218, 241; Janson (1987), Chromatographia 23, 361; Laurent (1993), J. Chromatogr. 633, 1]. These discoveries were the background to the development of a variety of affinity chromatographic methods. At present attempts are being made to combine size exclusion chromatography (SEC) with adsorption into a single operation that we call adsorptive SEC (AdSEC).     

Effective pulmonary blood flow in children with acute asthma attack requiring hospitalization

In children with acute obstructive lung disease gas exchange is affected by ventilation-perfusion mismatch and the degree of bronchoconstriction. Standard lung function measurements do not reflect the impairment in gas exchange. Alternatively, the effective pulmonary blood flow (EPBF), that is, the proportion of the cardiac output that is supplying well-ventilated lung units, can give accurate and noninvasive estimates of ventilation-perfusion mismatch. We measured EPBF with the argon freon-22 rebreathing technique in children with acute severe asthma to assess their response to nebulized salbutamol and to determine whether induced changes in the EPBF could be predicted from baseline measurements. Twenty-four children admitted with an acute asthma attack had spirometry and triplicate EPBF measurements before and after nebulized salbutamol. Eighteen patients had repeated tests 50 days later when fully recovered; 4 patients were taking methylxanthines on at least one occasion. The mean forced expiratory volume in 1 sec (FEV1) rose from 55% of predicted to 66% after salbutamol and to 83% with recovery. The mean coefficients of variation for EPBF measurements on the three test occasions were 11.3%, 8.2%, and 9%. Except in children on methylxanthines, the EPBF values were reduced during the acute asthma attack (median, 2.53 L/min/m2; range, 1.99-3.60 L/min/m2) compared with paired values obtained after recovery (median, 2.89 L/min/m2; range, 2.28-4.04 L/min/m2) (P = 0.009). Salbutamol caused a highly significant increase in EPBF from 2.88 L/min/m2 (range, 1.86-3.80) before treatment to 3.34 L/min/m2 (range, 2.26-4.65) immediately afterwards (P = 0.0003).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence of acute pulmonary embolism in central and subsegmental pulmonary arteries and relation to probability interpretation of ventilation/perfusion lung scans

PURPOSE: The purpose of this investigation is to determine the prevalence of acute pulmonary embolism (PE) limited to subsegmental pulmonary arteries. BACKGROUND: Contrast-enhanced helical (spiral) and electron-beam CT, in the hands of experienced radiologists who are skillful with this modality, are sensitive for the detection of acute PE in central pulmonary arteries, but have a low sensitivity for the detection of PE limited to subsegmental pulmonary arteries. The potential for CT to diagnose PE, therefore, is partially dependent on the prevalence of PE limited to subsegmental pulmonary arteries. METHODS: Data are from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). The largest pulmonary arteries that showed PE, as interpreted by the PIOPED angiographic readers, were identified in 375 patients in PIOPED with angiographically diagnosed PE. RESULTS: Among all patients with PE, 6% (95% confidence interval [CI], 4 to 9%) had PE limited to subsegmental branches of the pulmonary artery. Patients with high-probability ventilation/ perfusion (V/Q) scans had PE limited to subsegmental branches in only 1% (95% CI, 0 to 4%). Among patients with low-probability V/Q lung scans, 17% (95% CI, 8 to 29%) had PE limited to the subsegmental branches. Patients with low-probability V/Q scans and no prior cardiopulmonary disease had PE limited to the subsegmental pulmonary arteries in 30% (95% CI, 13 to 53%), whereas patients with low-probability V/Q scans who had prior cardiopulmonary disease had PE limited to subsegmental pulmonary arteries in 8% (95% CI, 2 to 22%) (p < 0.05). CONCLUSION: Based on data from all patients with PE in PIOPED, the prevalence of PE limited to subsegmental pulmonary arteries is low, 6%. PE limited to subsegmental pulmonary arteries was most prevalent among patients with low-probability V/Q scans, particularly if they had no prior cardiopulmonary disease.     

Noninvasive positive pressure ventilation: successful outcome in patients with acute lung injury/ARDS

A still unknown tricyclic heterocyclic system (5) was synthesized from 6-hydroxy-2-methylpyridazin-3-one and its structure identified as 2,8-dichloro-6-methylpyrrolo[1,2-b:3,4-d']dipyridazin-5(6H)- one by spectroscopic investigations. Selective condensation of 5 with 2-[4-(2-substituted-phenyl)piperazin-1-yl]ethylamine gave the 2-arylpiperazinylethylamino-8-chloro derivatives 6a-c, which were investigated in binding studies toward the three alpha1-adrenergic and 5-HT1A-serotonergic receptor subtypes. They displayed high potency on all the assays and some selectivity for alpha1a and alpha1d subtypes.     

The pulmonary uptake of intravenously administered liposomal alpha-tocopherol is augmented in acute lung injury

The present study was carried out to investigate whether the intravenous administration of liposomal alpha-tocopherol can result in a significant localization of the antioxidant in the injured lung. Male Sprague-Dawley rats were injected with paraquat dichloride (20 mg/kg, ip.) and 4, 24 or 48 h later, they were given an intravenous injection of a liposomal alpha-tocopherol preparation (20 mg alpha-tocopherol in 128 mumoles liposomal lipid/kg) labelled with [14C]dipalmitoylphosphatidylcholine (DPPC) and [3H]alpha-tocopherol. Animals were killed and their lungs removed for analysis 24 h after liposomal treatment. To demonstrate whether the extent of uptake of radioactive alpha-tocopherol liposomes was directly related to the extent of residual lung injury, additional groups of animals were also injected with higher doses (30 and 40 mg/kg body weight) of paraquat dichloride and 48 h later, were treated with liposomal alpha-tocopherol; animals were then killed 24 h after liposomal alpha-tocopherol treatment. The intraperitoneal injection of paraquat dichloride resulted in time- and dose-dependent decreases in angiotensin converting enzyme and alkaline phosphatase activities suggesting that the toxicant injures both the capillary endothelial cells and alveolar type II epithelial cells, respectively. The recovery of intravenously administered radioactive alpha-tocopherol in the lungs of saline-treated animals was found to be about 2% of the initial dose 24 h post-liposomal treatment. However, in paraquat-treated animals, there was an increased localization of the labelled alpha-tocopherol to the lung, resulting in a difference of pulmonary delivery by as much as 2-3 fold compared to that in a normal lung. The 3H/14C ratio, representing the recovery of [3H]alpha-tocopherol and [14C]liposomes, was practically constant and there was a linear relationship between the measurable lung injury index and the corresponding recovery of radiolabelled alpha-tocopherol in the lung. Our results appear to suggest that the residual pulmonary injury augments the delivery of liposomal alpha-tocopherol to the lung.