Histopathological Examination of the Effects of Tocilizumab and Dexamethasone on the Liver in Rats of Oleic Acid induced Acute Lung Injury

The mechanism of oxygenation improvement after recruitment manoeuvres or prone positioning in acute lung injury or acute respiratory distress syndrome is still unclear. We tried to determine the mechanism responsible for the effects of recruitment manoeuvres or prone positioning on lung aeration using a whole lung computed tomography scan in an oleic acid induced acute lung injury canine model. Twelve adult mongrel dogs were allocated into either the supine group (n=6) or the prone group (n = 6). After the establishment of acute lung injury, three recruitment manoeuvres were performed at one-hour intervals. Haemodynamic and ventilatory variables, arterial blood gas analyses and CT scans of the whole lung were obtained 90 minutes after oleic acid injection and five minutes before and after each recruitment manoeuvre. Recruitment manoeuvres in the supine position improved oxygenation (P=0.025) that correlated with increase of the poorly- and well-aerated dorsal (dependent) lung volume (r=0.436, P=0.016). Prone positioning increased oxygenation (P=0.004) that also correlated with increase of the poorly- and well-aerated dorsal (nondependent) lung volume (r=0.787, P <0.001). However, the recruitment manoeuvre in the prone position had no effect on oxygenation despite an increase in ventral (dependent) lung volume. The increase in PO2 after recruitment manoeuvres in the supine position or after prone positioning is related to the increase of the poorly- and well-aerated dorsal lung.

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Eicosanoid balance and perfusion redistribution of oleic acid-induced acute lung injury

Journal of Applied Physiology ◽

10.1152/jappl.1992.73.5.2126 ◽

1992 ◽

Vol 73 (5) ◽

pp. 2126-2134 ◽

Cited By ~ 20

Author(s):

A. H. Stephenson ◽

A. J. Lonigro ◽

S. W. Holmberg ◽

D. P. Schuster

Keyword(s):

Acute Lung Injury ◽

Oleic Acid ◽

Lung Injury ◽

Water Concentration ◽

Dependent Lung ◽

Lung Water ◽

Tissue Concentrations ◽

Tissue Samples ◽

Positron Emission ◽

Regional Lung

We have proposed that endogenous prostacyclin opposes the vasoconstriction responsible for redistribution of regional pulmonary blood flow (rPBF) away from areas of increased regional lung water concentration (rLWC) in canine oleic acid- (OA) induced acute lung injury (D. P. Schuster and J. Haller. J. Appl. Physiol. 69: 353–361, 1990). To test this hypothesis, we related regional lung tissue concentrations of 6-ketoprostaglandin (PG) F1 alpha and thromboxane (Tx) B2 in tissue samples obtained 2.5 h after administration of OA (0.08 ml/kg iv) to rPBF and rLWC measured by positron emission tomography. After OA only (n = 16), rLWC increased in dependent lung regions. Some animals responded to increased rLWC by redistribution of rPBF away from the most edematous regions (OA-R, n = 6), whereas others did not (OA-NR, n = 10). In another six animals, meclofenamate was administered after OA (OA-meclo). After OA, tissue concentrations of 6-keto-PGF1 alpha were greater than TxB2 in all groups, but concentrations of 6-keto-PGF1 alpha were not different between OA-R and OA-NR animals. TxB2 was increased in the dependent regions of animals in both OA-R and OA-NR groups compared with controls (no OA, n = 4, P < 0.05). The tissue TxB2/6-keto-PGF1 alpha ratio was smaller in controls and OA-NR in which no perfusion redistribution occurred than in OA-R and OA-meclo in which it did occur. This TxB2/6-keto-PGF1 alpha ratio correlated significantly with the magnitude of perfusion redistribution.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effect of eicosanoid inhibition on the development of pulmonary edema after acute lung injury

Journal of Applied Physiology ◽

10.1152/jappl.1996.80.3.915 ◽

1996 ◽

Vol 80 (3) ◽

pp. 915-923 ◽

Cited By ~ 24

Author(s):

D. P. Schuster ◽

A. H. Stephenson ◽

S. Holmberg ◽

P. Sandiford

Keyword(s):

Acute Lung Injury ◽

Oleic Acid ◽

Lung Injury ◽

Pulmonary Edema ◽

Experimental Models ◽

Nuclear Medicine Imaging ◽

Lung Water ◽

Edema Formation ◽

Cyclooxygenase Inhibition ◽

Positron Emission

In experimental models of acute lung injury, cyclooxygenase inhibition improves oxygenation, presumably by causing a redistribution of blood flow away from edematous lung regions. This effect on perfusion pattern could also reduce alveolar edema formation. On the other hand, pulmonary pressures usually increase after cyclooxygenase inhibition, an effect that could exacerbate edema accumulation. Therefore we tested the following hypothesis: the total accumulation of pulmonary edema in dogs during a 24- to 28-h period of observation after acute lung injury caused by oleic acid will be less in a group of animals treated with meclofenamate (n = 6) or with the thromboxane-receptor blocker ONO-3708 (n = 5) than in a group of animals treated with oleic acid alone (placebo, n = 6). Lung water concentrations (LWC), the regional pattern of pulmonary perfusion, and protein permeability were measured with the nuclear medicine imaging technique of positron emission tomography. After 24-28 h, LWC was significantly less (P < 0.05) in the ONO-3708 group than in the meclofenamate group (a similar trend was seen compared with the placebo group, P = 0.12). After 24-28 h, pulmonary arterial pressures were highest in the meclofenamate group. Regardless of group, the only significant correlation with the change in LWC was with the integral of pulmonary pressures over the 24- to 28-h period. The data suggest that thromboxane inhibition will reduce edema accumulation in acute lung injury but that this effect depends on reducing as much as possible the simultaneous development of pulmonary hypertension from other causes.

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