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J Czartolomna

Publications and source records attributed to J Czartolomna.

7 recordsLinked to original sources
PubMed1992

Role of eicosanoids in staphylococcal alpha-toxin-induced lung injury in the rat.

We investigated the role of arachidonic acid-derived eicosanoids in staphylococcal alpha-toxin (alpha-T)-induced lung injury. Bolus injection of 200 and 500 micrograms alpha-T into isolated perfused rat lungs resulted in increased pulmonary perfusion pressure followed by lung weight gain. Inhibition of pressure change with papaverine (10(-4) M) failed to abolish lung edema. Furthermore, alpha-T increased the permeability-surface area product in papaverine-treated lungs and caused marked endothelial cell injury and interstitial edema as documented by electron microscopy. alpha-T dose dependently increased lung tissue thromboxane B2 (TxB2) levels and leukotriene C4 levels. In lungs given 0, 200, and 500 micrograms of alpha-T, TxB2 (in micrograms/g wet lung) values were 16.3 +/- 2.8, 25.0 +/- 3.0, and 54.2 +/- 6.2; and leukotriene C4 values were 4.6 +/- 1.1, 6.7 +/- 1.2, and 22.1 +/- 3.8, respectively. Inhibition of cyclooxygenase enzyme with indomethacin (10(-5) M) or lipoxygenase enzyme with 2(12-hydroxydodeca-5,10-dinyl)-3,5,6-trimethyl-1,4-benzoq uin one (AA861, 10(-5) M) attenuated the vasoconstriction and prevented lung edema due to low dose (200 micrograms) but not high dose (500 micrograms) alpha-T. The protective effect of these inhibitors on lung edema is in part due to decreases in alpha-T-stimulated venoconstriction because alpha-T-induced increase in lung microvascular pressure was attenuated by indomethacin and AA861 pretreatment. We conclude that both eicosanoid-dependent and eicosanoid-independent mechanisms contribute to alpha-T-induced lung edema in the rat.

Animals↗
PubMed1992

Rapid onset of hypoxic vasoconstriction in isolated lungs.

A fast-response O2 analyzer that samples air at low flow rates allows the quasi-instantaneous measurement of O2 concentration change in the airways of isolated blood-perfused rat lungs. This instrument and an oximeter were used to measure the stimulus-response delay time of hypoxic pulmonary vasoconstriction when the lungs were challenged with 10, 5, or 3% O2. The estimate for the shortest delay time between accomplished fall in airway O2 concentration and the onset of hypoxia-induced vasoconstriction was approximately 7 s. We found that the slope of pressure rise, but not the stimulus-response delay time, correlated with the magnitude of hypoxic vasoconstriction. Oscillations in pulmonary arterial pressure were observed when the lungs were challenged with 10% O2 but not when the challenge was 12, 5, or 3%, indicating perhaps that these oscillations were a threshold phenomenon. Established hypoxic vasoconstriction was sensitive to brief changes in airway O2 concentration. Vasodilation occurred when the gas mixture was switched from 3 to 21% O2 for two to five breaths, and vasoconstriction occurred when the gas was changed during a single breath from 5 to 3% O2.

Animals↗
PubMed1992

FMLP causes eicosanoid-dependent vasoconstriction and edema in lungs from endotoxin-primed rats.

Recruitment of inflammatory cells to the lung capillaries has been proposed as an important step in the sequence of events that lead to acute lung injury. Frequently, in the clinical setting, bacteremia and sepsis syndrome precede the acute lung failure and endotoxin priming may represent a comparable paradigm, useful for experimental pursuit. Following addition of the chemotactic tripeptide FMLP (10(-9) to 10(-6) M) to the cell-free, salt solution perfusate of isolated rat lungs, only a small degree of vasoconstriction was observed. However, in lungs isolated from rats that received 2 mg/kg intraperitoneal Salmonella enteritidis endotoxin 2 h before lung perfusion, FMLP dose dependently caused a large, transient pulmonary pressor response, edema formation, and release of large amounts of thromboxane and leukotriene B4. Since in vitro priming with endotoxin, direct vascular injury by neutrophil elastase, nor direct stimulation with FMLP of pulmonary artery rings from endotoxin-pretreated rats, mimicked the effects of in vivo endotoxin priming, we conclude that the presence of inflammatory cells in the lung capillaries accounted for the large amount of eicosanoids produced by the lungs after FMLP stimulation. In fact, by retrograde lavage of the lung circulation with a collagenase solution, previously adherent cell clumps were mobilized and identified. These cell clumps, composed of red blood cells, neutrophils, and platelets, were not seen in the vascular lavage sediment obtained from unprimed control lungs. Indomethacin, a thromboxane antagonist, AA861, a 5-lipoxygenase inhibitor, and WEB 2086, a platelet-activating factor (PAF) antagonist, reduced the thromboxane synthesis and release after FMLP (10(-7) M) in in vivo endotoxin-primed lungs. None of the inhibitors employed exclusively inhibited only one particular eicosanoid mediator but rather affected the release of several mediators, suggesting a close link between the different synthetic arachidonic acid pathways. An inhibitor of phospholipase C (2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate), NCDC, but not an inhibitor of phospholipase D (Wortmannin) or of protein kinase C (staurosporine) inhibited the FMLP-stimulated pulmonary pressure rise and eicosanoid release in endotoxin-primed lungs in vivo. Our data suggest that eicosanoids (in particular thromboxane) released from cells trapped in the lung circulation, but not from constitutive lung cells, contribute to vasoconstriction and edema formation caused by the chemoattractant FMLP in endotoxin-primed lungs.

Alkaloids↗
PubMed1991

Permeability characteristics of isolated perfused rat lungs.

We examined the factors that influence the permeability characteristics of isolated perfused rat lungs and compared the ex vivo permeability-surface area product (PS) with that obtained in vivo. In lungs perfused for 20 min with homologous blood or a physiological salt solution (PSS) containing 4 g/100 ml albumin, mean PS values, obtained by the single-sample method of Kern et al. [Am. J. Physiol. 245 (Heart Circ. Physiol. 14): H229-H236, 1983], were 9.9 +/- 0.6 (SE) and 6.8 +/- 0.3 cm3.min-1.g wet lung-1.10(-2), respectively. These values were similar to lung PS obtained in intact rats (7.7 +/- 0.4 cm3.min-1.g wet lung-1.10(-2). In perfused lungs, PS values were influenced by the perfusate albumin concentration, the length of perfusion time, and the degree of vascular recruitment. Twenty minutes after lung isolation, PS was 126% higher in lungs perfused with albumin-free PSS containing Ficoll than in lungs perfused with albumin-PSS. Moreover, PS in Ficoll-PSS-perfused lungs increased even higher after 2 h of perfusion, and this time-dependent increase in PS was attenuated by addition of 0.1 g/100 ml albumin to the perfusate. Two hours of ex vivo ventilation with hypoxic (0 or 3% 0(2)) or hyperoxic (95% 0(2)) gas mixture did not affect PS values in perfused lungs. However, PS was elevated in lungs perfused ex vivo with protamine, which causes endothelial cell injury, or in lungs from rats exposed in vivo to human recombinant tumor necrosis factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Vanadate potentiates hypoxic pulmonary vasoconstriction.

Vanadate, an essential trace element and an inhibitor or stimulator of many enzymes, potentiates the hypoxic vasoconstriction in isolated lung preparations. However, the mechanism of action of vanadate in the lung circulation is unclear. We compared, in isolated rat lungs, the effect of vanadate (3 x 10(-5) M) on hypoxia-induced vasoconstriction with the vasoconstriction caused by angiotensin II, KCl or NaCN, and found that vanadate preferentially enhanced the hypoxia- and NaCN-induced pressor responses. Vanadate also shifted the stimulus-response curve for oxygen such that vasoconstriction occurred at a higher PO2 than in control lungs, indicating that vanadate had affected the oxygen sensing mechanism in the lungs. We postulated that vanadate might potentiate hypoxic vasoconstriction, in part, by activating a protein kinase C (PKC), and compared the effect of phorbol myristate acetate (PMA; 5 x 10(-8) M) on hypoxic vasoconstriction with that of vanadate. Both agents, PMA and vanadate, potentiated hypoxic vasoconstriction transiently and to a similar degree and the potentiation by both agents was blocked by staurosporine (1 microgram/ml), a PKC inhibitor, and 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate, a phospholipase C inhibitor, and partially reduced by the Ca++ entry inhibitor nifedipine. We conclude that the similarities between the action of PMA and vanadate in isolated lungs point toward an involvement of the PKC in the mechanism of vanadate-induced potentiation of hypoxic vasoconstriction. In addition, our data indicate that potentiation of hypoxic vasoconstriction by PMA or vanadate may occur, in part, independent of voltage-dependent Ca++ entry.

Animals↗
PubMed1990

Role of peptidoleukotrieens in hypoxic pulmonary vasoconstriction in rats.

The role of leukotrienes in the mechanism of hypoxic pulmonary vasoconstriction (HPV) is controversial. To determine whether leukotriene C4 (LTC4) was produced during HPV, LTC4 levels were measured in individual samples of lung tissue, lung bronchoalveolar lavage fluid (BALF), and blood perfusate in isolated perfused lungs ventilated with normoxic or hypoxic gas mixtures. HPV was not associated with increased LTC4 in lung tissue or increased LTE4 in blood perfusate. Consistent with previous studies demonstrating elevated levels of LTC4 in pooled BALF fluid from hypoxic lungs, individual lung BALF samples demonstrated an elevation of LTC4 during hypoxia. However, the process of lung lavage alone stimulated eicosanoid production, with LTC4, 6-ketoprostaglandin F1 alpha, and thromboxane B2 levels being higher in lavaged compared to non-lavaged lungs. In lungs to which the lipoxygenase inhibitor AA 861 was added to the perfusate, a reduction in the lung tissue LTC4 levels was observed without any or only a slight reduction in HPV. To evaluate the physiological effects of LTC4 in the airways, exogenous LTC4 (1-1,000 ng) was added to the airways of both blood- and physiological salt solution-perfused lungs without any effect on the pulmonary artery pressure or a response to hypoxia. These results do not support the hypothesis that leukotrienes mediate HPV in the rat.

Animals↗