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D Walmrath

Publications and source records attributed to D Walmrath.

79 records · Page 5Linked to original sources
PubMed1990

Leukotriene and hydroxyeicosatetraenoic acid generation elicited by low doses of Escherichia coli hemolysin in rabbit lungs.

Low doses of Escherichia coli hemolysin cause thromboxane-mediated hypertension and vascular leakage in blood-free perfused rabbit lungs (W. Seeger, H. Walter, N. Suttorp, M. Muhly, and S. Bhakdi, J. Clin. Invest. 84:220-227, 1989). The recirculating buffer medium and bronchoalveolar lavage fluid from lungs exposed to hemolysin (2.5 hemolytic units per ml) in the presence of cyclooxygenase inhibitor were analyzed for leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) by reverse-phase and straight-phase high-pressure liquid chromatographic techniques combined with UV spectrum analysis and post-high-pressure liquid chromatography radioimmunoassay. A rapid release of large amounts of cysteinyl-LTs and leukotriene B4 (LTB4) into the intravascular space was noted (total sum, approximately 4 to 5 micrograms). Similar quantities have hitherto been elicited only by high concentrations of the artificial calcium ionophore A 23187. Moreover, a marked liberation of 5-HETE and 12-hydroxyheptadecatrienoic acid into the buffer medium occurred, whereas LTB4 represented the predominant compound in the lavage fluid. The hemolysin-induced burst of LT and HETE generation preceded the onset of vascular leakage. The outstanding capacity of E. coli hemolysin to produce the liberation of potent lipid mediators is probably relevant to the pathways of vascular injury and amplification of inflammatory events during severe infection with hemolytic E. coli strains.

Animals↗
PubMed1987

Arachidonic acid lipoxygenase pathways and increased vascular permeability in isolated rabbit lungs.

Products of arachidonic acid (AA) pathways have repeatedly been implicated in acute lung vascular injury with respiratory distress. In blood-free perfused isolated rabbit lungs, AA endogenously released or exogenously applied causes an acute pressor response, mediated by metabolites of the cyclooxygenase pathway including thromboxane A2. Moreover, bolus application of AA (final concentration, 100 microM in the recirculating buffer) during an acute hydrostatic challenge was recently noted to cause a rapid, severalfold increase in the capillary filtration coefficient (Kf,c), though any significant rise in pulmonary vascular pressure was inhibited by indomethacin. In the present study, we showed that during this mode of AA bolus application in cell-free perfused rabbit lungs, microgram amounts of peptidoleukotrienes (LTE4 greater than LTC4 greater than LTD4) and LTB4 were released into the recirculating buffer within 5 min and continued to be released even after 2 exchanges of the perfusion fluid. In the presence of 2 structurally unrelated lipoxygenase inhibitors (nordihydroguaiaretic acid and AA-861), the leukotriene release was nearly completely inhibited and the AA-induced severe increase in vascular permeability was significantly reduced (2.5- to 3-fold rise in Kf,c, compared to a greater than 10-fold increase in Kf,c in the absence of lipoxygenase inhibition). Exogenous LTC4 caused a dose-dependent, sustained pressure rise in protein-free perfused lungs, apparently mediated via the pulmonary generation of AA cyclooxygenase products. Bolus application of 10 micrograms LTC4 or LTD4 or 7.5 micrograms LTB4 in protein-free perfused lungs during an acute hydrostatic challenge did not, however, mimic the AA bolus-induced severalfold increase in vascular permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Fibronectin decreases pulmonary vascular permeability under baseline conditions and after administration of arachidonic acid in rabbit lungs.

In blood- and plasma-free perfused isolated rabbit lungs, the influence of albumin and soluble fibronectin on vascular permeability was investigated. The lungs were perfused with Krebs Henseleit buffer containing no protein (KHB), containing 1 g/100 ml bovine albumin (KHAB) or containing albumin together with 100 micrograms/ml soluble fibronectin. The absence or presence of albumin had no influence on the perfusion pressure, the vascular compliance and the capillary filtration coefficient (CFC), determined by zero time extrapolation of the slope of weight gain which was induced by a sudden venous pressure elevation. Fibronectin caused a slight increase in pulmonary artery pressure, a slight decrease in vascular compliance and an approximately 50% reduction of CFC. In a second set of experiments, KHAB-perfused lungs were stimulated by the administration of 100 microM arachidonic acid (AA) during the second hydrostatic challenge within a sequence of three venous pressure elevations. In the presence of indomethacin, which blocks any significant increase in pulmonary vascular pressure after AA application, this procedure caused an immediate gain in lung weight due to increased pulmonary vascular permeability, with greater than 10-fold increased CFC values subsequent to the AA application. In the presence of 100 micrograms/ml fibronectin, this AA-induced increase in CFC was mitigated to less than 20% of the controls without the glycoprotein, with correspondingly severalfold reduced lung weight gain. In conclusion, the present study provides evidence for a direct influence of circulating soluble fibronectin on lung microvascular integrity and fluid balance under baseline conditions and after stimulation of the pulmonary AA cascade.

Animals↗
PubMed1986

Pulmonary microvascular injury induced by Pseudomonas aeruginosa cytotoxin in isolated rabbit lungs.

The effects of Pseudomonas aeruginosa cytotoxin on the pulmonary microvasculature were studied in blood-free, perfused, isolated rabbit lungs. Cytotoxin was administered to the recirculating Krebs Henseleit albumin (1%) buffer during two consecutive 30-min-perfusion phases (phases 1 and 2) at a concentration of 13 micrograms/ml, followed by a third perfusion phase (phase 3) without toxin. After perfusion phases 2 and 3, the capillary filtration coefficient (Kf,c) and vascular compliance were determined gravimetrically from two-step microvascular pressure increments under zero-flow conditions. Cytotoxin caused a continuous release of K+ and lactate dehydrogenase, which started within the first 5 min and amounted to about 50% of the total lung cellular K+ and 5 to 7% of the total lactate dehydrogenase by the end of the experiment. The toxin caused the continuous generation of prostaglandin I2, which was detectable in the perfusates of all perfusion phases at maximum values five times above the control values and which was measured in the bronchoalveolar lavage fluid at the end of the experiment. Thromboxane generation in toxin-treated lungs did not significantly exceed that of control lungs or of lungs with mechanically induced edema. Cytotoxin caused a gradual increase in pulmonary vascular resistance, to maximum values 2.5 times above the control, starting within 1 min; the increase was partially reversible after washout of the toxin. After a lag period of 20 to 30 min, the lungs gained weight, amounting to a mean gain of 9.1 g at the end of the experiments. After perfusion phases 2 and 3, an almost fourfold increase in Kf,c, which was not reversible after washout of the toxin, was measured, whereas the values of vascular compliance were not altered. We conclude that pseudomonal cytotoxin may be an important factor in the pathogenesis of prolonged microvascular injury, encountered in states of P. aeruginosa sepsis or acute lung failure with secondarily acquired P. aeruginosa pneumonia.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Increased lung vascular permeability after arachidonic acid and hydrostatic challenge.

Arachidonic acid (AA) metabolites are known to be potent vasoactive substances in the pulmonary circulation, whereas their influence on lung vascular permeability is still uncertain. We investigated the effect of AA bolus injection on the capillary filtration coefficient (Kf,C) of isolated rabbit lungs, recirculatingly perfused with Krebs-Henseleit albumin (1%) buffer. Kf,C was measured using repetitive sudden venous pressure elevations (7.5 Torr) and time zero extrapolation of the slope of the weight gain curve. It ranged from 1.3 to 2.4 cm3 X s-1 X Torr-1 X g-1 X 10(-4) in control lungs. Pulmonary arterial injection of AA (100 microM; in presence of 20 microM indomethacin to suppress pulmonary arterial pressure rise) during an acute hydrostatic challenge, but not at zero venous pressure, caused a greater than 10-fold increase in Kf,C. Vascular compliance was not altered. Additional experiments, performed under zero-flow conditions to avoid any ambiguity in microvascular pressure, corroborated the severalfold increase in vascular permeability, detectable within 3 min after AA application during acute hydrostatic challenge.

Animals↗
PubMed1985

Influence of the thromboxane antagonist BM 13.177 on the arachidonic acid-induced increase in pulmonary vascular resistance and permeability in rabbit lungs.

UNLABELLED: In blood-free perfused isolated rabbit lungs increased availability of free arachidonic acid (AA), whether exogenously applied or released from the endogenous membrane phospholipid pool after different stimuli, causes an acute pulmonary artery pressor response and an increase in vascular permeability. Previous experiments suggested that the vasoconstriction is caused primarily by the cyclooxygenase product thromboxane (Tx) A2, whereas an increase in the capillary filtration coefficient must be ascribed to non-cyclooxygenase products of AA. The influence of BM 13.177, a non-prostanoic antagonist of TxA2- and endoperoxide-effects in platelets, on the AA-induced vascular effects in isolated rabbit lungs was investigated. BM 13.177 dose-dependently inhibited the pressor responses evoked by repetitive direct application of AA (IC50 approximately 10(-6) M) or by repetitive stimulation of endogenous AA-release with the calcium-ionophore A 23187 (IC50 approximately 10(-7) M), with maximum reduction of the pressor responses to less than 15%. The generation of TxA2 and of prostaglandin (PG) I2 evoked by these stimuli was, however, not altered. At a concentration of 10(-5) M BM 13.177 did not influence the capillary filtration coefficient, measured during venous pressure challenge, under baseline conditions and after stimulation with AA in presence of indomethacin. CONCLUSION: BM 13.177 acts as TxA2/endoperoxide antagonist with dose-dependent inhibition of AA-induced vasoconstriction in the pulmonary vascular bed.

6-Ketoprostaglandin F1 alpha↗