PubMed HealthSearch

PubMed · 389115

Failure of positive end-expiratory pressure to decrease lung water content in alloxan-induced pulmonary edema.

Abstract

The effect of 10 cm H2O of positive end-expiratory pressure (PEEP) on pulmonary extravascular water volume (PEWV) was measured in an animal model of noncardiogenic pulmonary edema. Three groups of animals were studied: (1) controls, (2) those given a saline infusion plus alloxan, and (3) those which received saline infusion plus alloxan and PEEP. All animals were ventilated with a constant volume ventilator. Mean PEWV (+/- SEM) in milliliters per gram of dry lung weight was 4.00 +/- 0.21 for group 1, 6.01 +/- 0.70 for group 2, and 5.77 +/- 0.83 for group 3. Mean PEWV increased significantly in both alloxan groups (groups 2 and 3) as compared to the control group (for both, p less than 0.05); however, PEWV did not differ significantly in the group that received PEEP, as compared to the group ventilated without PEEP. Arterial PO2 and airway pressure required to deliver a constant tidal volume did not change significantly in the experimental groups as compared to the control group. It was concluded that PEEP does not decrease lung water content in pulmonary edema caused by damage to fluid-exchanging vessels.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

P C Hopewell. 1979. Failure of positive end-expiratory pressure to decrease lung water content in alloxan-induced pulmonary edema.. https://doi.org/10.1164/arrd.1979.120.4.813

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Statistical geometry of pancreatic islets.

Quantitative histomorphometric studies of the dynamics of growth and development of pancreatic islets in normal and pathological states pose substantial methodological and conceptual problems. We address these problems with the geometry of random fractals, and apply our methods to the analysis of islet regeneration in the alloxan-treated guinea-pig. In both experimental islet-regenerated and control animals, islet centres are found to cluster in similar fractal subsets of dimension strictly less than 3, in agreement with the postulated origin of islets along a system of ductules, and suggesting that regeneration follows the same mathematical dynamics as original islet formation.

Alloxan

Effects of alloxan and ninhydrin on mitochondrial Ca2+ transport.

Alloxan at millimolar concentrations slightly inhibited the velocity of Ca2+ uptake by isolated rat liver mitochondria irrespective of the free Ca2+ concentration between 1 and 10 microM and was an effective concentration-dependent stimulator of mitochondrial Ca2+ efflux. Ninhydrin also slightly inhibited the velocity of mitochondrial Ca2+ uptake but only at free Ca2+ concentrations above 5 microM. However, ninhydrin was a strong stimulator of mitochondrial Ca2+ efflux even at micromolar concentrations, 10-50 times more potent than alloxan. The mitochondrial membrane potential was reduced 10-20% at most by alloxan and ninhydrin. Alloxan and ninhydrin also stimulated Ca2+ efflux from isolated permeabilized liver cells. When isolated intact liver cells had been pre-incubated with alloxan or ninhydrin before permeabilization of the cells the ability of spermine to induce mitochondrial Ca2+ uptake was abolished. Glucose provided the typical protection against the effects of alloxan on mitochondrial Ca2+ transport only in experiments with intact cells but not in experiments with permeabilized cells or isolated mitochondria. Therefore glucose protection is apparently due to inhibition of alloxan uptake into the cell. Glucose provided no protection against effects of ninhydrin under any of the experimental conditions. Thus both alloxan and ninhydrin are potent stimulators of Ca2+ efflux by isolated mitochondria but very weak inhibitors of the velocity of mitochondrial Ca2+ uptake. The direct effects of ninhydrin on mitochondrial Ca2+ efflux may contribute to the cytotoxic action of this agent whereas the direct effects of alloxan on mitochondrial Ca2+ transport require concentrations which are too high to be of relevance for the induction of the typical pancreatic B-cell toxic effects of alloxan. However, the effects on mitochondrial Ca2+ transport during incubation of intact cells which may result from the generation of cytotoxic intermediates during alloxan xenobiotic metabolism may well contribute to the pancreatic B-cell toxic effect of alloxan.

Alloxan

Possible mechanism of immunosuppressive effect of scoparone (6,7-dimethoxycoumarin).

The possible mechanism of the immunosuppressive effect of scoparone (6,7-dimethoxycoumarin) was investigated. Human peripheral blood mononuclear cells (10(6) cells/ml) were stimulated with 0.25% phytohemagglutinin (PHA) and the proliferative response was determined from the uptake of tritiated thymidine. Scoparone (10(-6) to 3 x 10(-4) M) reduced the proliferative response in a dose-dependent manner. The proliferative response of mononuclear cells to mixed lymphocyte reaction was also reduced by scoparone (10(-5) to 10(-4) M). Interleukin-1, interleukin-2 production and interleukin-2 receptor expression were all reduced in the presence of scoparone. Scoparone (10 and 30 microM) significantly reduced the suppression elicited by the diabetogenic drug, alloxan (10 mM). The suppressive activity of scoparone was significantly reduced by quinacrine (a phospholipase A2 inhibitor), indomethacin (a cyclooxygenase inhibitor) and nordihydroguaiaretic acid (a lipoxygenase inhibitor). The levels of prostaglandin E2, prostaglandin F2 alpha, leukotriene B4 and 2,3-dinor-thromboxane B2 in culture medium of PHA-stimulated mononuclear cells, measured with an enzyme immunoassay, were elevated by scoparone treatment. We compared the effect of scoparone on the mononuclear cell response to genistein, a specific inhibitor of protein tyrosine kinase and demonstrated the non-additivity and cross-desensitization of the two compounds. Our results suggest that the immunosuppressive effect of scoparone may be exerted in part through inhibition of protein tyrosine kinase and release of arachidonic acid metabolites.

Alloxan