Thromboxane and prostacyclin production in the perfused rabbit lung.
We investigated whether prostacyclin formation by the isolated rabbit lung can serve as a measure of pulmonary distress. The basal TXA2 and PGI2 formation was very low, and depended on the preperfusion history of the lung (low or high flow, use of dextran or artificial perfusate). The basal prostanoid production remained unchanged over a time period of 2 h. Neither was it influenced by the serotonin uptake inhibitor chlorimipramine and by small changes in temperature (33 degrees C vs 39 degrees C). The PGI2 formation was almost independent of hemodynamic alterations such as embolism or vasoconstriction. An enhanced production was only seen after a dramatic increase in flow (from 1.7-5 ml/sec), and a transient 3-fold increase was observed after administration of 1 mM H2O2. A substantial (up to 40-fold) but transient increase in TXA2 production was measured after 1 mM of H2O2, and the TXA2 production was positively correlated to the increase in pulmonary arterial pressure. However, thromboxane production was also dramatically augmented by hemodynamic alterations such as embolism, increased flow and--to a lesser extent--vasoconstriction. We conclude that the determination of the prostanoid production (and particularly the TXA2 formation) by the rabbit lung cannot be used as a direct measure of endothelial distress. To this end it is excessively biased by hemodynamic alterations such as recruitment and shear stress.
Peeters
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FA
University of Antwerp (UIA), Faculty of Medicine, Division of Pharmacology, Wilrijk, Belgium.
Van den Bossche
R
R
Bult
H
H
Herman
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AG
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011652:Pulmonary Circulation / Q000502:physiology; D011817:Rabbits; D013312:Stress, Physiological / Q000378:metabolism; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000096:biosynthesis
D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol