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S Rosseau

Publications and source records attributed to S Rosseau.

36 records · Page 2Linked to original sources
PubMed1997

Sequestration of the alveolar bone by invasive aspergillosis in acute myeloid leukemia.

Compared to non-invasive aspergillosis, invasive aspergillosis in the region of the mouth, jaw and face has rarely been reported. It occurs particularly often in the presence of haematological oncological illness. The case of a patient suffering from acute myeloid leukemia is described; he contracted invasive aspergillosis of the lungs and the alveolar processes in the course of chemotherapeutic treatment. All the alveolar processes in the region of the premolars and molars were demarcated and had to be removed by sequestrectomy. The therapy of invasive aspergillosis should be carried out within the framework of intensive interdisciplinary treatment. In addition to systemic and local antimycotic therapy, the debridement of necrotic hard and soft tissue was necessary.

Acute Disease↗
PubMed1997

Plasma free iron: a possible cause of oedema in kwashiorkor.

BACKGROUND: Oedema is a sine qua non for the diagnosis of kwashiorkor yet the mechanisms leading to oedema remain ill defined. AIMS: To relate the plasma concentration of radical promoting 'free' iron to the degree of oedema in patients with kwashiorkor. SETTING: University teaching hospital. PATIENTS: Fifteen children with kwashiorkor, nine of whom had severe and six of whom had a moderate degree of oedema. METHODS: Plasma 'free' iron was measured as bleomycin detectable iron (BDI) and related to severity of oedema and plasma albumin concentration. RESULTS: BDI was significantly higher in the patients with severe oedema (20.5 v 6.75 mumol/l) whereas the albumin concentrations were similar (16 v 17 g/l). BDI was no longer present in any patients 30 days after admission. CONCLUSIONS: 'Free' circulating iron may contribute to the oedema of kwashiorkor, and its sequestration could hasten recovery and decrease morbidity and mortality.

Child↗
PubMed1997

Separation of human alveolar macrophages by flow cytometry.

Alveolar macrophages (AM), which represent the major resident population of immunocompetent cells in the lower respiratory tract, have been implicated in the pathogenesis of acute lung injury in view of their exceptional capacity to release a large array of inflammatory mediators. The ex vivo analysis of these cells, accessible to bronchoalveolar lavage (BAL) is hampered by the fact that, under conditions of respiratory failure, the AM pool is heavily expanded by polymorphonuclear neutrophils (PMN), which necessitates separation of these cell populations. In the present study, we describe a flow cytometric approach to sort human AM obtained from BAL samples of both healthy volunteers (n = 10) and patients with severe pneumonia demanding mechanical ventilation (n = 10), using forward scatter and high autofluorescence characteristics to discriminate AM from PMN and lymphocytes. This technique yielded highly purified AM populations (>95%) as evidenced by morphological analysis, cytochemistry, and CD71 and CD14 expression of the sorted cells. The flow sorting process, per se, did not induce the expression of the acute-phase cytokine tumor necrosis factor-alpha (TNF-alpha) in control AM as determined by reverse transcriptase-polymerase chain reaction. Unstimulated and lipopolysaccharide-induced TNF-alpha protein secretion were comparable in sorted and unsorted AM as demonstrated by enzyme-linked immunosorbent assay. We suggest flow sorting of viable human AM as an efficient and nonperturbing separation technique to yield highly purified cell populations especially from PMN-rich BAL fluids of critically ill patients.

Antigens, CD↗
PubMed1997

Endotoxin priming of thromboxane-related vasoconstrictor responses in perfused rabbit lungs.

In prior studies of perfused lungs, endotoxin priming markedly enhanced thromboxane (Tx) generation and Tx-mediated vasoconstriction in response to secondarily applied bacterial exotoxins. The present study addressed this aspect in more detail by employing precursor and intermediates of prostanoid synthesis and performing functional testing of vasoreactivity and measurement of product formation. Rabbit lungs were buffer perfused in the absence or presence of 10 ng/ml endotoxin. Repetitive intravascular bolus applications of free arachidonic acid provoked constant pulmonary arterial pressor responses and constant release reactions of TxA2 and prostaglandin (PG) I2 in nonprimed lungs. Within 60-90 min of endotoxin recirculation, which provoked progressive liberation of tumor necrosis factor-alpha but did not effect any hemodynamic changes by itself, both pressor responses and prostanoid release markedly increased, and both events were fully blocked by cyclooxygenase (Cyclo) inhibition with acetylsalicylic acid (ASA). The unstable intermediate PGG2 provoked moderate pressor responses, again enhanced by preceding endotoxin priming and fully suppressed by ASA. Vasoconstriction also occurred in response to the direct Cyclo product PGH2, again amplified after endotoxin pretreatment, together with markedly enhanced liberation of TxA2 and PGI2. In the presence of ASA, the priming-related increase in pressor responses and the prostanoid formation were blocked, but baseline vasoconstrictor responses corresponding to those in nonprimed lungs were maintained. Pressor responses to the stable Tx analog U-46619 were not significantly increased by endotoxin pretreatment, but some generation of TxA2 and PGI2 was also noted under these conditions. We conclude that endotoxin priming exerts profound effects on the lung vascular prostanoid metabolism, increasing the readiness to react with Tx-mediated vasoconstrictor responses to various stimuli, suggesting that enhanced Cyclo activity is an important underlying event.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Synergism between endotoxin priming and exotoxin challenge in provoking severe vascular leakage in rabbit lungs.

Lipopolysaccharides (LPS) of gram-negative bacteria prime rabbit lungs for enhanced thromboxane-mediated vasoconstriction upon subsequent challenge with the exotoxin Escherichia coli hemolysin (HlyA) (Walmrath et al. J. Exp. Med. 1994;180:1437-1443). We investigated the impact of endotoxin priming and subsequent HlyA challenge on lung vascular permeability while maintaining constancy of capillary pressure. Rabbit lungs were perfused in a pressure-controlled mode in the presence of the thromboxane receptor antagonist BM 13.505, with continuous monitoring of flow. Perfusion for 180 min with 10 ng/ml LPS did not provoke vasoconstriction or alteration of capillary filtration coefficient (Kfc) values. HlyA (0.021 hemolytic units/ml) induced thromboxane release and a transient decrease in perfusion flow in the absence of significant changes in Kfc. Similar results were obtained when LPS and HlyA were coapplied simultaneously. However, when the HlyA challenge was undertaken after 180 min of LPS priming, a manifold increase in Kfc values was noted, with concomitant severe lung edema formation, although capillary pressure remained unchanged. Thus, endotoxin primes the lung vasculature to respond with a severe increase in vascular permeability to a subsequent low-dose application of HlyA. Such synergism between endotoxin priming and exotoxin challenge in provoking lung vascular leakage may contribute to the pathogenesis of respiratory failure in sepsis and severe lung infection.

Animals↗
PubMed1996

Escherichia coli hemolysin and Staphylococcus aureas alpha-toxin potently induce neutrophil adhesion to cultured human endothelial cells.

Adhesion of polymorphonuclear leukocytes (PMN) to endothelial cells is an essential step in inflammatory reactions. We characterized the effects of two important bacterial exotoxins, Escherichia coli hemolysin (HlyA) and Staphylococcus aureus alpha-toxin (S. alpha-toxin) on PMN adhesion to cultured HUVEC. Both toxins increased adherence of human PMN to HUVEC in a dose- and time-dependent manner, peaking after 30 min at 0.01 hemolytic units/ml HlyA or 0.5 microg/ml S. alpha-toxin. Pretreatment of HUVEC with anti-P-selectin mAbs or of PMN with anti-CD11b/CD18 mAb reduced HlyA- and S. alpha-toxin-related cell adhesion significantly. Increased P-selectin expression on toxin-treated endothelial cells was demonstrated by cell surface ELISA. Compared with endotoxin, HlyA and S. alpha-toxin did not induce the expression of E-selectin, ICAM-1, or VCAM-1. FACS analysis showed increased CD11b/CD18 expression on HlyA-, but not on S. alpha-toxin-stimulated PMN. Platelet-activating factor, an important costimulatory factor for PMN adhesion and activation, was also active in the exotoxin-stimulated adhesion system, as evidenced by studies using the platelet-activating factor receptor antagonist BN50727. HPLC analysis of endothelial cell extracts confirmed enhanced toxin-mediated PAF synthesis. The capacity of exotoxins to stimulate PMN adhesion to endothelial cells may be relevant in patients with severe local or systemic bacterial infections.

Azepines↗
PubMed1996

Compartmentalized lung cytokine release in response to intravascular and alveolar endotoxin challenge.

Lung cytokine generation has been implicated in pulmonary injury and systemic inflammatory responses. In bufferperfused rabbit lungs, intravascular endotoxin (10 ng/ml perfusate; total amount 7 micrograms) provoked the liberation of 212,100 +/- 119,700 pg tumor necrosis factor-alpha (TNF-alpha) into the vascular space within 3 h. This was augmented to 3,564,400 +/- 1,285,900 pg in the presence of 1% serum. Bronchoalveolar lavages demonstrated the absence of buffer-admixed endotoxin and transition of only minor fractions of the vascular TNF-alpha load into the alveolar space. Aerosolization of 22 micrograms endotoxin liberated 824,400 +/- 48,750 pg TNF-alpha into the alveolar compartment, which was even increased to 16,980,000 +/- 6,066,350 pg on co-nebulization of serum. No endotoxin and only minor amounts of the alveolar TNF-alpha burden spilled over into the vascular compartment. Vascular pressures and lung vascular permeability did not change. We conclude that both intravascular and alveolar endotoxin challenge provokes excessive lung TNF-alpha generation, amplified manyfold in the presence of small serum quantities. For both routes of application, however, the cytokine responses were found to be largely compartmentalized under the given conditions of integer lung barrier properties.

Aerosols↗
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↗
PubMed1996

Bone marrow and chelatable iron in patients with protein energy malnutrition.

OBJECTIVES: To examine the iron status of malnourished children by comparing bone marrow iron deposits in children with protein energy malnutrition with those in well-nourished controls, and measuring chelatable urinary iron excretion in children with kwashiorkor. DESIGN: Bone marrow iron was assessed histologically in postmortem specimens from children with kwashiorkor or marasmus, and from controls. Twenty-four-hour urinary iron was measured in children with severe kwashiorkor, half of whom received 10 mg/kg of intramuscular desferrioxamine (DFO) on admission. SETTING: Red Cross War Memorial Children's Hospital, Cape Town. SUBJECTS: Thirteen children with kwashiorkor, 6 with marasmus and 16 well-nourished children underwent bone marrow examination. Urinary iron excretion was assayed in 17 children with kwashiorkor. RESULTS: Stainable iron was present in the bone marrow of half the children with kwashiorkor but in only 1 child in each of the other groups. The median iron excretion was 945.5 micrograms/24 hours in the DFO group compared with 28.5 micrograms/24 hours in the non-DFO group. CONCLUSIONS: There is an apparent excess of iron which may predispose to bacterial infections and free radical-mediated injury in children with kwashiorkor.

Bone Marrow↗
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

Surfactant incorporation markedly alters mechanical properties of a fibrin clot.

Intra-alveolar clot formation is a common finding in acute and chronic inflammatory lung diseases. Incorporation of lipophilic surfactant components into a growing fibrin clot has recently been reported (Am. J. Respir. Cell Mol. Biol. 1993; 9:213-220). In the present study, we investigated the influence of such surfactant incorporation on the elastic properties and water permeability of the fibrin polymer. Thrombelastography and compaction experiments were employed for assessment of the elastic properties, and the permeability characteristics of the clot material were addressed in fibrin-packed columns. Two calf lung surfactant extracts (CLSE and Alveofact), Curosurf, and a synthetic phospholipid mixture (dipalmitoylphosphatidylcholine, phosphatidylglycerol, and palmitic acid at a ratio of 68.5:22.5:9 [wt/wt]) were used. The presence of surfactant did not affect the cleavage of fibrinopeptide A upon incubation of fibrinogen with thrombin (enzyme-linked immunosorbent assay technique). Similarly, kinetics and extent of factor XIII-induced covalent crosslinkage of the fibrin network remained unchanged in the presence of surfactant (sodium dodecyl sulfate polyacrylamide gel electrophoresis and D-Dimer quantification upon subsequent clot lysis). All surfactants, however, dose-dependently decreased the elastic modulus of the arising fibrin polymer. The maximal amplitude in thrombelastography was reduced, and the recovery of fluid after centrifugation of the fibrin clot increased. Fibrin clots embedding natural surfactant material displayed reduced permeability for saline as compared with control fibrin polymers. Subsequent washout of lipids from these clots with Triton X-100 resulted in increased hydraulic conductivity. This was accompanied by an increase in pore size, suggesting altered architecture of the fibrin matrix generated in the presence of surfactant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Misplaced iron in kwashiorkor.

OBJECTIVES: To determine the presence of radical promoting iron (non-protein-bound or loosely bound or free iron) in the plasma of children with kwashiorkor. DESIGN: The bleomycin assay was employed for the quantitation of free or loosely bound iron. SETTING: The Red Cross War Memorial Children's Hospital, Cape Town, Tertiary Care. SUBJECTS: Fifty children on admission with kwashiorkor: six with marasmus and twelve healthy well-nourished controls. RESULTS: Non-protein-bound iron was detected in the plasma of 58% of children with kwashiorkor but was absent in marasmic and healthy well-nourished children. CONCLUSIONS: The presence of radical promoting iron supports the hypothesis that a free radical injury probably plays a role in the pathogenesis of kwashiorkor and its removal may improve mortality.

Bleomycin↗
PubMed1994

Endotoxin "priming" potentiates lung vascular abnormalities in response to Escherichia coli hemolysin: an example of synergism between endo- and exotoxin.

The pore-forming hemolysin of Escherichia coli (HlyA), an important virulence factor in extraintestinal E. coli infections, causes thromboxane generation and related vasoconstriction in perfused rabbit lungs (Seeger, W., H. Walter, N. Suttorp, M. Muhly, and S. Bhakdi. 1989. J. Clin. Invest. 84:220). We investigated the influence of pulmonary vascular "priming" with endotoxin on the responsiveness of the lung to a low-dose HlyA challenge. Rabbit lungs were perfused with Krebs Henseleit buffer containing 0.1-100 ng/ml Salmonella abortus equii lipopolysaccharide (LPS) for 60-180 min. This treatment caused protracted release of tumor necrosis factor into the recirculating medium, but did not induce significant alterations of pulmonary hemodynamics and fluid balance. At a dose of 1 ng/ml, HlyA elicited only moderate thromboxane release (< 200 pg/ml) and pulmonary artery pressure increase (< or = 6 mmHg) in control lungs. Acceleration and potentiation of both the metabolic and vasoconstrictor response occurred in lungs primed with LPS. This priming effect displayed dose (threshold integral of 0.1-1 ng/ml LPS) and time dependencies (threshold integral of 60-90 min LPS incubation). Maximum thromboxane release and pulmonary artery pressure increase surpassed the responses to HlyA in nonprimed lungs by more than 15-fold. Cyclooxygenase inhibition and thromboxane-receptor antagonism blocked these effects. These data demonstrate that LPS priming synergizes with HlyA challenge to provoke vascular abnormalities that are possibly relevant to the pathogenesis of organ failure in severe local and systemic infections.

Animals↗
PubMed1994

Multiparameter flow cytometric analysis of inflammatory cells contained in bronchoalveolar lavage fluid.

Quantitative analysis of surface molecule expression on viable alveolar macrophages (AM) by use of flow cytometry is hampered by non-specific antibody binding to various AM FcIgG receptors as well as extensive and heterogeneous autofluorescence of this cell type. The following approaches were undertaken to circumvent these obstacles. FcIgG receptors were blocked by excess human immunoglobulin. The use of a long wave-emitting dye (phycoerythrin/cyanine-5 tandem conjugate) permitted avoidance of the peak (green) AM autofluorescence range. Moreover, a cell-by-cell compensation for the remaining red autofluorescence background was employed. This was based on two facts: (i) strict correlation between green (F488/530) and red autofluorescence (F488/660) for all AM populations investigated; and (ii) neglectable overlap of the antibody-associated red fluorescence into the 530 nm autofluorescence detection wavelength. A fraction of the green autofluorescence (F488/530; channel 1) was then subtracted from the red fluorescence (F488/660; channel 2) on a cell-by-cell basis using standard two colour fluorescence compensation circuits. The validity of this FACS technique was confirmed by comparison with immunocytochemical staining and a reverse rosetting method. On AM lavaged from carcinoma-bearing but otherwise disease-free human lungs, the pattern of surface antigen expression was assessed with a panel of monoclonal antibodies. When applying to complex mixtures of bronchoalveolar lavage cells, the autofluorescence was employed to separate AM from granulocytes and lymphocytes. In conclusion, the presently described FACS technique allows quantitative immunostaining of surface molecules on AM, even when present in low copy numbers on highly autofluorescent cells originating from smokers.

Bronchoalveolar Lavage Fluid↗
PubMed1994

Morphometric analysis of pulmonary intracapillary leukocyte pools in ex vivo-perfused rabbit lungs.

Characterization and quantification of lung intracapillary leukocytes is of interest for a better understanding of immunological and inflammatory features in this organ. We developed a technique of computer-assisted measurement of digitalized electron-microscopic images and electronic data processing for morphometry of intracapillary leukocyte pools in rabbit lungs (L. Ermert, W. Seeger, and H.-R. Duncker, Cell Tissue Res. 271: 469-476, 1993). Measurements were undertaken in buffer-perfused isolated lungs (avoiding any reentry of washed-out cells); perfusion fixation was performed 7.5, 35, and 185 min after onset of artificial circulation (n = 5 each). Data were compared with that of nonperfused lungs fixed by tracheal instillation (baseline). Total lung capillary neutrophil counts were 1.41 x 10(9), 1.35 x 10(9), 1.37 x 10(9), and 0.69 x 10(9) (baseline, 7.5, 35, and 185 min perfusion, respectively). Corresponding data for intracapillary lymphocytes were 1.07 x 10(9), 0.84 x 10(9), 0.81 x 10(9), and 0.57 x 10(9); and for microvascular monocytes, data were 0.21 x 10(9), 0.19 x 10(9), 0.18 x 10(9), and 0.08 x 10(9). Ratios of cell volume and surface variables of the different intracapillary leukocyte types did not change during ex vivo lung perfusion. We conclude that the rabbit pulmonary capillary bed harbors large pools of different leukocytes, which surpass pool sizes of corresponding circulating cells and display very slow washout kinetics under conditions of lung-buffer perfusion. A major impact of these intracapillary leukocyte pools on immunological and inflammatory events in isolated-perfused and transplanted lungs must be assumed.

Animals↗
PubMed1994

Phagocytosis of viable Candida albicans by alveolar macrophages: flow cytometric quantification.

The phagocytic capacity of blood leukocytes may be assessed by flow cytometric techniques using fluorochrome-labeled particles including viable microorganisms. Application of this approach to alveolar macrophages (AM) is hampered or even rendered impossible by the strong autofluorescence of this cell type, superimposing the fluorescence intensity of the labeled phagocytic targets. Viable Candida albicans were loaded with the membrane-permeable fluorescent dye carboxy-seminaphtorhodafluor 2/acetoxymethylester (carboxy-SNARF 2-AM), which is cleaved intracellularly to generate the membrane-impermeable derivative carboxy-SNARF 2. Fluorescence was excited with the 488-nm line of an argon-ion laser, and the emission peak at 633 nm was used for quantification of dye-associated fluorescence. Rabbit and human AM were labeled with fluorescein isothiocyanate-coupled monoclonal mouse anti-macrophage antibodies. After coincubation of macrophages and yeast, 4% paraformaldehyde plus 0.5% EDTA in phosphate-buffered saline was used to stop the phagocytic process and detach adherent yeast from the AM surface. Macrophages loaded with yeast displayed a shift from monochromatic (green) to dual (green and red) fluorescence. The percentage of yeast-positive AM and red fluorescence intensity of phagocytosing macrophages were quantified. Yeast opsonization with serum or anti-Candida immunoglobulins was a prerequisite for phagocytosis. Under optimized conditions (0.5-10% serum; 60 min yeast-AM incubation; yeast-AM ratio 8:1 to 12:1), 71-91% of the AM were involved in the phagocytic process. Yeast engulfment was completely inhibited by N-ethylmaleimide and iodoacetic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Neutrophil passage through isolated perfused rabbit lungs.

Kinetics of polymorphonuclear leukocyte (PMN) lung passage were investigated in ex vivo isolated and ventilated left rabbit lungs, perfused with buffer solution at physiological flow rate. 111In-labeled PMNs of rabbit or human origin were injected into the pulmonary artery, and the first fraction of PMNs that rapidly passed the lung together with coinjected erythrocytes, was collected separately for external radioactivity counting. Washout of initially retained PMNs from the lung was monitored by use of a sodium-iodide detector. Recirculation of cells was avoided by insertion of a filter in the perfusion circuit. A fraction of 16.6 +/- 1.3% of rabbit PMNs rapidly passed the lung vasculature, followed by an exponential washout of initially retained PMNs [half-time (t50) of lung transit 8.1 +/- 0.6 min]. Slightly higher t50 (12.2 +/- 1.0 min) was obtained upon use of human PMNs. Reduction in flow by 50% caused a marked prolongation of PMN transit (t50 = 27.8 +/- 5.1 min), whereas increase in flow to 150% only insignificantly decreased t50. Rise in pulmonary venous pressure to 5 and 8 mmHg caused retardation of PMN lung transit (t50 = 15.3 +/- 0.6 and 31.6 +/- 3.6 min). Preincubation of PMNs with 2 ng/ml endotoxin for 1 h induced marked delay in PMN washout (t50 = 26.1 +/- 2.8 min). In conclusion, single-pass PMN kinetics in isolated lungs correspond to in vivo studies previously reported, thus allowing elucidation of PMN-endothelial interactions in an intact lung vasculature under standardized conditions.

Animals↗