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W Seeger

Publications and source records attributed to W Seeger.

At least 199 records · Page 11Linked to original sources
PubMed1996

Differential role of actin in lung endothelial and epithelial barrier properties in perfused rabbit lungs.

Lung fluid balance is critically dependent on capillary endothelial and alveolar epithelial barrier properties, and cytoskeletal components have been implicated in these barrier functions. In an earlier study, we perfused Clostridium botulinum C2 toxin, which effects selective loss of non-muscle F-actin, through isolated rabbit lungs: a severalfold increase in the capillary filtration coefficient (Kfc) was noted, together with attenuations and disruptions of endothelial cells upon electron microscopic examination. In this model we have investigated the influence of the C2 toxin on alveolar epithelial barrier properties. Epithelial permeability was assessed by continuous monitoring of the transepithelial passage of technetium-labelled diethylenetriamine penta-acetic acid (99mTc-DTPA), offered to the alveolar surface by aerosol technique. Intravascular administration of hydrogen peroxide, used as control agent, was shown to provoke a four- to fivefold increase in the clearance rate of 99mTc-DTPA under conditions of severe fluid leakage into the lung interstitial and alveolar space. Intravascular administration of C2 toxin caused a dose- and time-dependent increase in Kfc values (8-15 fold), but the Tc-DTPA clearance rate was entirely unaffected. Moreover, transbronchial application of C2 toxin again reproduced the manifold increase in Kfc data (about six fold), but the rate of transepithelial passage of the hydrophilic Tc-DTPA complex remained unchanged. We conclude that the barrier properties of the lung microvascular endothelial and epithelial layer are differentially regulated. It is suggested that the actin microfilament system plays a decisive role in the structural and functional integrity of the endothelial but not the epithelial barrier.

Actins↗
PubMed1996

Bronchoalveolar and systemic cytokine profiles in patients with ARDS, severe pneumonia and cardiogenic pulmonary oedema.

The aim of this study was to investigate whether bronchoalveolar lavage (BAL) and serum levels of proinflammatory cytokines discriminate between different entities of patients with acute respiratory failure. BAL and circulating concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) were measured in 74 mechanically-ventilated patients and 17 healthy controls. Patients were classified as cardiogenic pulmonary oedema (CPO), acute respiratory distress syndrome (ARDS), primary severe pneumonia (PN) and a combined group (PN+ARDS). In all patients with ARDS and/or PN, markedly elevated BAL levels of IL-6 and IL-8 were detected, which were significantly greater than levels in CPO and healthy controls. Absolute quantities and time-course of these cytokines did not differentiate between the absence and presence of lung infection, or different categories of PN. Similarly, circulating IL-6 levels were comparably elevated in patients with ARDS and/or PN, whereas circulating IL-8 concentrations were inconsistently increased. TNF-alpha was rarely detected in BAL samples, but increased serum concentrations were measured in ARDS and/or PN patients. Bronchoalveolar lavage levels of interleukin-6 and interleukin-8, but not tumour necrosis factor-alpha, and serum concentrations of interleukin-6 are consistently elevated in acute respiratory distress syndrome and/or severe pneumonia, discriminating these entities from cardiogenic pulmonary oedema. Alveolar and systemic cytokine profiles do not differentiate between acute respiratory distress syndrome in the absence of lung infection and states of severe primary or secondary pneumonia, which evidently present with comparable local and systemic inflammatory sequelae.

Acute Disease↗
PubMed1995

Hydrogen peroxide-induced increase in lung endothelial and epithelial permeability--effect of adenylate cyclase stimulation and phosphodiesterase inhibition.

Neutrophil-derived hydrogen peroxide (H2O2) is believed to play an important role in inflammatory lung injury. We investigated the influence of pharmacological agents that increase intracellular c-AMP levels on endothelial and epithelial leakage in response to intravascular H2O2 challenge in buffer-perfused rabbit lungs. Endothelial permeability was assessed by determination of the capillary filtration coefficient (Kfc) and lung weight gain. Measurement of the clearance rate of inhaled aerosolized technetium-99m-labeled diethylenetriamine pentaacetic acid ([99mTc]DTPA) from the lungs into the perfusion fluid was used as an index of alveolar epithelial permeability. Experiments were performed in the presence of acetylsalicylic acid to suppress H2O2-induced lung prostanoid generation and concomitant vasoconstriction. Under these conditions, H2O2 admixture to the perfusate (250 microM) caused a greater than eight-fold increase in Kfc values, resulting in > 30 g lung weight gain within 30 min in the absence of any significant vasopressor response. Pretreatment with the adenylate cyclase activators prostaglandin E1 (0.1 microM) and forskolin (0.1 microM), the dual phosphodiesterase type III/IV inhibitor zardaverine (10 microM) as well as combinations of these drugs all caused a nearly complete suppression of this early Kfc increase; and severe edema formation (> 30 g) was retarded to approximately 50-55 min. In addition to the microvascular leakage response, H2O2 caused a four- to five-fold increase in the [99mTc]DTPA clearance rate, starting within 15 min and culminating after approximately 35 min. Adenylate cyclase activation reduced this epithelial leakage response by approximately 30%, whereas zardaverine exerted no significant effect. We conclude that both microvascular endothelial and alveolar epithelial barrier function are severely compromised by intravascular H2O2 challenge in intact lungs. Pharmacological approaches to increase c-AMP levels, including both adenylate cyclase activation and phosphodiesterase inhibition, partially block the endothelial response and, to a lesser extent, the epithelial response.

Adenylyl Cyclases↗
PubMed1995

Prevention and therapy of the adult respiratory distress syndrome.

The complex pathophysiology of adult respiratory distress syndrome (ARDS) makes preventive and therapeutic concepts difficult. Ample experimental evidence indicates that ARDS can be prevented by blocking systemic inflammatory agents. Clinically, only heparin, for inhibition of coagulation phenomena, is presently used among this array of approaches. Corticosteroids have not proven to be beneficial in ARDS. Alternative antiinflammatory agents are being proposed and are under current clinical investigation (e.g. indomethacin, acetylcysteine, alpha 1-proteinase inhibitor, antitumor necrosis factor, interleukin 1 receptor antagonist, platelet-activating factor antagonists). Symptomatic therapeutic strategies in early ARDS include selective pulmonary vasodilation (preferably by inhaled vasorelaxant agents) and optimal fluid balance. Transbronchial surfactant application, presently tested in pilot studies, may be available for ARDS patients in the near future and may have acute beneficial effects on gas exchange, pulmonary mechanics, and lung hemodynamics; its impact on survival cannot be predicted at the present time. Strong efforts should be taken to reduce secondary nosocomial pneumonia in ARDS patients and thus avoid the vicious circle of pneumonia, sepsis from lung infection, and perpetuation of multiple organ dysfunction syndrome. Optimal respirator therapy should be directed to ameliorate gas-exchange conditions acutely but at the same time should aim at minimizing potentially aggravating side effects of artificial ventilation (barotrauma, O2 toxicity). Several new techniques of mechanical ventilation and the concept of permissive hypercapnia address these aspects. Approaches with extracorporeal CO2 removal and oxygenation are being used in specialized centers.

Humans↗
PubMed1995

Staging, scoring and grading of medulloblastoma. A postoperative prognosis predicting system based on the cases of a single institute.

Although recently survival of some medulloblastoma patients increased remarkably, it remains a serious diagnosis in others. In order to predict the postoperative prognosis in patients treated for medulloblastoma, a new staging, scoring and grading system was developed. Sixty-six patients operated on microsurgically between 1975 and 1990 at a single neurosurgical center were fully followed-up. No patient was excluded due to a poor postoperative course. Completion of commonly used radiotherapy protocols was attempted in all patients. Survival of patients was evaluated by the Kaplan-Meier method. The following 5 parameters were selected to define subgroups: patients' age, tumour location and histology, degree of resection and presence or absence of metastases. Patients older than 10 years had a better prognosis than individuals aged 10 or less (p < 0.01), patients with lateral tumours had a better prognosis than patients with midline tumours with brain stem infiltration (p < 0.05), patients with complete tumour resection had a more favourable prognosis than individuals with subtotal (p < 0.01) or partial resection (p < 0.001), patients without metastases at the time of diagnosis had a better prognosis than individuals without such evidence (p < 0.001), patients with the desmoplastic tumour variant had a better prognosis than patients with classical tumour histology (p < 0.01). According to the prognosis of a distinct subgroup, scoring points were distributed which correlated with the degree of inter-subgroup significances. The sum of a single patient's scoring points was called the total score. Based on this score, three groups of prognosis were distinguished.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Parkinsonism and rest tremor secondary to supratentorial tumours sparing the basal ganglia.

Intracranial neoplasms are an uncommon cause of symptomatic Parkinsonism and rest tremor. We found an incidence of 0.3% in a prospective evaluation of 907 patients with supratentorial tumours. Eight patients with Parkinsonism and rest tremor secondary to supratentorial tumours sparing the basal ganglia are reported. Neuro-imaging revealed compression and distortion of the basal ganglia by large tumours which were identified histopathologically as meningiomas in four patients and as an epidermoid, a fibrillary astrocytoma, an anaplastic oligodendroglioma and a glioblastoma. Six patients underwent tumour removal by craniotomy, in two the histopathology was obtained by stereotactic biopsy. Four patients were free of Parkinsonian symptoms and signs on long-term follow-up. The possible pathophysiological mechanisms involved are discussed. Since some of these patients closely resemble cases of idiopathic Parkinson's disease, and the movement disorder can precede other symptoms and signs or will remain isolated in the further course, the diagnosis of an intracranial neoplasm was generally delayed in these patients. Increased awareness of this rare entity may lead to an earlier diagnosis. Early computed tomography in patients with Parkinsonism might help to detect these patients with a potentially curable cause of their condition.

Adult↗
PubMed1995

Secondary manifestation of medulloblastoma: metastases and local recurrences in 66 patients.

Although primary treatment of medulloblastoma is now successful in a high percentage of patients, its secondary manifestations still bear a poor prognosis. Thorough studies of secondary manifestations are therefore pivotal to plan therapeutic approaches for the long-term management of medulloblastoma. Here we describe the incidence of secondary tumour manifestations in 66 patients of a single centre who underwent surgery for medulloblastoma between 1975 and 1990. No patient was excluded due to a poor postoperative course. Thirty-five patients showed evidence of secondary tumour growth. Of these, 17 suffered from local recurrence, and 27 developed metastastatic disease. The median latencies for secondary manifestations were 25 months for local recurrence (n = 17), 11 months for spinal metastases (n = 10), 15 months for supratentorial metastases (n = 8), 8 months for subleptomeningeal dissemination (n = 6), and 23 months for systemic metastases (n = 8). Two patients developed primary metastatic spread to the posterior fossa. Of 8 patients with supratentorial metastases, 6 developed fronto-basal lesions. In our patients, 89% of secondary lesions occurred within less than 3 years after primary diagnosis. 85% of patients with extra-axial tumour spread had been treated with a permanent shunt. Radical tumour resection and radiotherapy with 30 Gy to the neuraxis and 20 Gy boost to the posterior fossa was an important prognostic factor in this series. Patients with additional chemotherapy did not benefit significantly from this treatment. We conclude that optimal management of the primary lesions should aim at (i) total resection, (ii) avoid permanent shunting, and (iii) completion of the radiotherapy with inclusion of the medial frontobasal cisterns in the radiotherapeutic regimen. Our analysis suggests that adequate postoperative screening programmes should consist of 3-monthly scans of the neuraxis in the first three postoperative years and 6-monthly scans thereafter.

Adolescent↗
PubMed1995

The relation of intracranial pressure B-waves to different sleep stages in patients with suspected normal pressure hydrocephalus.

The interpretation of data from continuous monitoring of intracranial pressure (ICP) in patients with suspected normal pressure hydrocephalus (NPH) is the subject of controversy. Despite the fact that overnight ICP monitoring is widely used for the diagnosis of NPH, normative criteria are poorly defined. The present study demonstrates that there is a relationship between the relative frequency, the absolute amplitude, the wavelength and the morphology of B-waves and different sleep stages. Intraventricular intracranial pressure was recorded continuously overnight in 16 patients with suspected normal pressure hydrocephalus. Simultaneous polysomnography was performed to investigate the relation of spontaneous ICP oscillations to different sleep stages. A correlative analysis was done with the data of 13 patients. Three patients were excluded, one who was awake throughout the night and two in whom polysomnography was incomplete due to technical reasons. The mean resting cerebrospinal fluid (CSF) pressure was 12.87 cm CSF. B-waves were observed in the ICP recordings of all patients. They were present for a mean of 72% of the total recording time. The relative frequency of B-waves was higher during REM sleep and sleep stage 2 as compared to wakefulness (87.8% and 83.2% vs. 56. p < 0.05). The absolute amplitude was higher during REM sleep than in wakefulness (9.56 vs. 3.44 cm CSF, p < 0.05). Wavelengths were longer in REM sleep than in wakefulness and stages 1 and 2 (62.4 vs. 42, 40.7 and 44.8 sec, p < 0.05). The morphology of B-waves was also related to different sleep stages. Ramp-type B-waves were associated with REM sleep in six patients, however, were also present in sleep stage 2 in three of them. Knowledge of the relation of spontaneous ICP oscillations to different sleep stages may help to establish physiological foundations and alterations. Furthermore, polysomnography may be useful to avoid erroneous interpretation of ICP recordings due to sleep stage related variability.

Adult↗
PubMed1995

Hypoxic vasoconstriction in buffer-perfused rabbit lungs.

Isolated rabbit lungs were buffer-perfused under constant flow-conditions with separate control of alveolar (PAO2) and mixed venous (PvO2) O2 tension. Alveolar hypoxia caused an increase in pulmonary artery pressure (PAP) with sigmoidal dose-dependency. Erythrocytes increased the strength of the hypoxic pulmonary vasoconstriction (HPV). The contractile and vasorelaxant responses to the onset and release of alveolar hypoxia, respectively, occurred within seconds. Kinetics of the PAP increase, but not the magnitude of response, were related to the velocity of PAO2 decline. In contrast, changes in PvO2, both in the absence and presence of erythrocytes, did neither provoke any pressor response nor amplify the response to concomitant alveolar hypoxia. Repeatedly performed HPV manoeuvres revealed excellent reproducibility, and long-term alveolar hypoxia (90 min) provoked a biphasic pressor response. We conclude that the isolated rabbit lung is a feasible model for the characterization of hypoxic vasoconstriction, with specific features hitherto not described for perfused lungs of other species.

Animals↗
PubMed1995

Liquid movements in ventilated and perfused isolated lungs of fetal sheep at 0.87, 0.90, and 0.95 of term.

To study lung liquid movements, an isolated lung model, adapted from adult physiology, was developed to measure pulmonary weight changes after the onset of artificial ventilation of lungs from 16 fetal sheep at 0.87 (n = 5), 0.90 (n = 6), and 0.95 (n = 5) of gestation. The fetuses were delivered by Caesarean section. After tracheotomy and thoracotomy under general anaesthesia, a blocked air-free tracheal cannula and a pulmonary arterial catheter were inserted and secured to ensure in situ perfusion of the pulmonary circulation (Krebs-Henseleit buffer) without ventilation before the lungs were removed from the chest and mounted in a specially designed apparatus. Lung weight and pulmonary perfusion pressure were recorded continuously before, during and after the onset of ventilation. After 50 min of ventilation the perfusate was allowed to recirculate and samples were taken at 10-min intervals to determine the concentrations of sodium and the activity of lactate dehydrogenase (LDH) as a marker for cell destruction. In all lungs studied there was a significant removal of lung liquid after the onset of ventilation as assessed by lung weight loss. However, there was a positive correlation between lung weight loss and gestational age of the donor fetuses. These changes were accompanied by a rise in sodium concentrations in the perfusate, possibly suggesting that active sodium transport across the pulmonary epithelium facilitates alveolar liquid removal. As the experiments progressed the lungs regained weight while LDH concentrations increased, indicating that lung cell destruction causing pulmonary oedema may be involved. This pulmonary weight gain was inversely related to gestational age. It is concluded that in isolated ventilated and perfused lungs from fetal sheep, lung liquid removal is an age-related phenomenon that might involve an active sodium transport mechanism. It is further concluded that the development of pulmonary oedema during ventilation is also age related.

Animals↗
PubMed1995

Differential influence of arachidonic vs. eicosapentaenoic acid on experimental pulmonary hypertension.

The impact of the 2- and 3-series prostanoid precursors arachidonic acid (AA) and eicosapentaenoic acid (EPA) on experimental pulmonary hypertension was investigated. The model of buffer-perfused rabbit lungs was stimulated by infusion of Escherichia coli hemolysin (HlyA), which is known to provoke sustained thromboxane (Tx)-mediated pulmonary hypertension. Release of di- and trienoic Tx into the recirculating perfusate was quantified by a post-high-performance liquid chromatography enzyme-linked immunosorbent assay technique. HlyA at 0.08 hemolytic unit/ml caused a sustained rise in pulmonary arterial pressure (PAP; maximum increase 14 +/- 2 mmHg) accompanied by progressive TxB2 liberation (maximum perfusate concn 33 +/- 4 pg/ml, baseline < 2 pg/ml). Between 5 and 30 nM, AA provoked a transient monophasic rise in PAP (maximum pressor response 1.5-15 mmHg) and concomitant TxB2 release (peak concn 2-30 pg/ml). Simultaneous administration of HlyA and AA exhibited additive effects with regard to mediator release and pressor responses. EPA at 200-2,000 nM caused a transient rise in PAP similar to that provoked by 5-30 nM AA (maximum pressor response 3-18 mmHg). This was accompanied by liberation of TxB2 (peak concn 16 +/- 5 and 28 +/- 4 pg/ml after 1,000 and 2,000 nM EPA) and TxB3 (peak concn 9 +/- 4 and 30 +/- 3 pg/ml). Combined application of HlyA and EPA resulted in approximate addition of the TxB2 release reaction to each single compound, and TxB3 liberation more than doubled (maximum concn 59 +/- 12 pg/ml). The pressor responses to HlyA-EPA (200-2,000 nM) did not, however, surpass those to HlyA-AA (5-30 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of NADPH oxidase inhibitors on hypoxic vasoconstriction in buffer-perfused rabbit lungs.

The involvement of NADPH oxidase in hypoxic pulmonary vasoconstriction (HPV) was investigated in buffer-perfused rabbit lungs, employing the inhibitors diphenyleneiodonium (DPI) and apocynin. Responses to the vasoconstrictors U-46619 and angiotensin II (ANG II) were used to test specificity. Lung nitric oxide (NO) generation was assessed by on-line monitoring of NO exhalation (chemiluminescence), and the efficacy of DPI and apocynin on the NADPH oxidase-dependent O2- generation was quantified in alveolar macrophages by fluorescent-activated cell sorter technique. In a concentration range between 1 and 5 mM, apocynin inhibited macrophage respiratory burst and HPV but similarly suppressed U-46619-induced vasoconstrictor responses. DPI inhibited macrophage O2- generation in concentrations > or = 0.5 microM. At doses between 0.5 and 1.5 microM, DPI blocked lung NO generation, thereby increasing HPV. At higher doses (4 microM), in contrast, DPI fully blocked the hypoxia-induced pressor responses, whereas the vasoconstrictor responses to U-46619 and [Asn1, Val5] ANG II were not diminished. In the presence of NG-monomethyl-L-arginine, used to block lung NO generation throughout, DPI exhibited only the monophasic selective inhibition of HPV. We conclude that apocynin lacks specificity for HPV, but DPI, in addition to inhibiting lung NO generation, causes selective blockade of the hypoxia-induced vasoconstriction. This finding supports the hypothesis that an NADPH oxidase is involved in hypoxia sensing or specific signal transduction events underlying HPV.

Acetophenones↗
PubMed1995

Role of endothelial cytoskeleton in high-permeability edema due to botulinum C2 toxin in perfused rabbit lungs.

The cytoskeleton of the endothelial cell has been suggested to regulate endothelial barrier function. We investigated the role of actin in the maintenance of pulmonary capillary integrity in perfused rabbit lungs. As a tool for selective perturbation of actin, we employed Clostridium botulinum C2 toxin, which is composed of a membrane translocation component (C2II) and a component (C2I) effecting ADP-ribosylation of nonmuscle G-actin. ADP-ribosylated actin no longer capable of polymerization but acts as a barbed end-capping protein, thereby effecting selective loss of the nonmuscle F-actin content. In buffer-perfused rabbit lungs, combined application of both toxin components (range 50 pg/ml-5 ng/ml C2I) resulted in a time- and dose-dependent increase in the capillary filtration coefficient (Kfc) with concomitant edema formation. Only 300:600 pg/ml C2I:II sufficed to induce a > 10-fold rise of Kfc values within 110 min. This severe lung permeability increase occurred in the absence of vasomotor responses and potassium release or lactate dehydrogenase release. Application of each single toxin component displayed markedly reduced efficacy. Similar to the C2 toxin effect, severe permeability increase without concomitant hemodynamic changes was evoked by cytochalasin D, known to possess F-actin-disrupting properties. Preloading of lung cells with phallacidin, which in opposition to C2 toxin decreases F-actin depolymerization, significantly reduced the C2 toxin-induced increase in vascular permeability. Electron microscopic examination of C2 toxin-poisoned lungs showed early, extensive endothelial cell attenuations, followed by disruptions of the endothelial layer and marked interstitial edema formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

On-line measurement of nitric oxide generation in buffer-perfused rabbit lungs.

In buffer-perfused rabbit lungs, the mixed expired gas was continuously analyzed for nitric oxide (NO) by chemiluminescence detection, and recovery data in dependency of the alveolar O2 tension were established. A small aliquot of the lung effluent was continuously forwarded to a reaction vessel in which the NO decomposition products nitrite, peroxynitrite, and nitrate [summarized as NOx; acidic vanadium (III) chloride reagent] or nitrite (acidic sodium iodide reagent) were quantitatively reduced back to NO, which was then transferred to a second chemiluminescence detector. Under baseline conditions, the perfused lungs continuously released 2.2 +/- 0.21 nmol/min of NO (n = 10) into the gas space. NO was permanently liberated into the intravascular compartment at 7.0 +/- 0.3 nmol/min (n = 4). According to a very low buffer-gas partition coefficient of NO (estimated to be 0.0292 +/- 0.005 in separate equilibration experiments), NO aerated into the prelung perfusate largely escaped into the alveolar space within one lung passage, whereas only low percentages of inhaled NO were detected as NOx in the buffer medium. Immediate increase of lung NO generation in response to A-23187 challenge and inhibition by NG-monomethyl-L-arginine were demonstrated. In conclusion, in buffer-perfused lungs, total NO generation may be monitored by continuous analysis of NO exhalation and perfusate NOx accumulation.

Animals↗
PubMed1995

Nitric oxide generation and hypoxic vasoconstriction in buffer-perfused rabbit lungs.

Nitric oxide generation and hypoxic vasoconstriction in buffer-perfused rabbit lungs. J. Appl. Physiol. 78(4): 1509-1515, 1995.--We investigated the role of nitric oxide (NO) generation in hypoxic pulmonary vasoconstriction in buffer-perfused rabbit lungs. Exhaled NO was detected by chemiluminescence, and intravascular NO release was quantified as perfusate accumulation of nitrite, peroxynitrite, and nitrate (NOx). Under baseline conditions, exhaled NO was 45.3 +/- 4.1 parts per billion (1.8 +/- 0.2 nmol/min), and lung NOx release into the perfusate was 4.1 +/- 0.4 nmol/min. Alveolar hypoxia (alveolar PO2 of approximately 23 Torr) induced readily reproducible pressor responses preceded by a sharp drop in exhaled NO concentration. In contrast, perfusate NOx accumulation was not affected. Vasoconstrictor responses to U-46619 and angiotensin II were not accompanied by a decrease in NO exhalation. NG-monomethyl-L-arginine dose-dependently suppressed NO exhalation and amplified pressor responses to hypoxia > U-46619 and angiotensin II. In conclusion, portions of baseline NO generation originating from sites with ready access to the gaseous space sharply decrease in response to alveolar hypoxia, whereas the intravascular release of NO is unchanged. Such differential regulation of lung NO synthesis in response to hypoxia may suggest a complex role in the regulation or modulation of hypoxic pulmonary vasoconstriction.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Effects of aerosolized prostacyclin in severe pneumonia. Impact of fibrosis.

The effects of aerosolized prostaglandin (PG) I2 on gas exchange and hemodynamics were investigated in patients ventilated mechanically because of severe community-acquired pneumonia. Group A were patients without preexisting lung disease (n = 6), and Group B were those with underlying chronic fibrotic interstitial lung disease (n = 6). Ventilation-perfusion distribution was assessed by the multiple inert gas elimination technique. In Group A, low doses of aerosolized PGI2 (mean, 6.6 +/- 3.0 ng/kg/min) sufficed to decrease the mean pulmonary artery pressure (Ppa) from 35.0 +/- 1.5 to 31.0 +/- 1.6 mm Hg (p < 0.05), to improve the ratio of arterial oxygen to the fraction of inspired oxygen (PaO2/FIO2 increase from 100 +/- 18 to 134 +/- 18; p < 0.05), and to decrease intrapulmonary shunt (36.9 +/- 4.7 to 27.5 +/- 4.5%; p < 0.05). Systemic arterial pressure (Psa) and cardiac output remained unchanged. In Group B, aerosolized PGI2 was ineffective in doses less than 10 ng/kg/min. A dosage of 33.6 +/- 12 ng/kg/min reduced Ppa (38.0 +/- 2.4 to 30.8 +/- 2.1 mm Hg; p < 0.05), but it also decreased Psa (80.3 +/- 3.6 to 71.3 +/- 4.7 mm Hg; NS) and PaO2/FIO2 (73.8 +/- 6.6 to 65.5 +/- 6.8 mm Hg; p < 0.05) values and increased intrapulmonary shunt (44.7 +/- 3.0 to 49.4 +/- 5.0%, NS). After withdrawal of the PGI2 aerosol, all gas exchange and hemodynamic changes returned to preaerosol baseline values within 60 min in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1995

ELISA technique for quantification of surfactant protein B (SP-B) in bronchoalveolar lavage fluid.

Surfactant protein B (SP-B) is one of the essential constituents of the alveolar surfactant system, presenting mainly in the form of SP-B dimer. The measurement of this molecule in biologic samples has been hampered by its extreme hydrophobicity and intimate association with surfactant lipids. We developed a solid-phase, adsorption-based enzyme-linked immunosorbent assay (ELISA) technique for the quantification of SP-B in aqueous solutions. The ELISA employs the hydrophobicity of SP-B for direct binding of this compound to polystyrol immunosorbent plates. Samples are mixed with propanol (1:1 vol/vol) to achieve a homogeneous dispersion of their lipophilic constituents prior to adsorption to the wells. After fluid removal by evaporation, trifluoroethanol is added to optimize SP-B-polystyrol binding, and is then removed, again by evaporation. Subsequent washing procedures (diisopropyl-ether/butanol; Tween 20 in phosphate buffered saline [PBS]) selectively remove phospholipids. Solid phase-bound SP-B is detected by a monoclonal mouse antibody against porcine SP-B, cross-reacting with the apoprotein of human origin. For amplification, a biotinylated anti-mouse antibody and the avidin/biotin-peroxidase technique are used. Steep calibration curves with an excellent reproducibility are obtained for SP-B dimer (range: 0.3125 to 40 ng/well), either introduced directly into the immunosorbent-plate wells or previously admixed with synthetic phospholipid mixtures. SP-B monomer is detected with approximately 10% efficiency as compared with the dimer (wt/wt). Cross-reactivities with human SP-A and SP-C or albumin are negligible. Experiments with spiking of human bronchoalveolar lavage fluid (BAL) samples with different quantities of SP-B dimer revealed virtually complete apoprotein recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗