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Effect of 16,16-dimethyl prostaglandin E2 on oxygen uptake and microcirculation in the perfused rat liver

✍ Scribed by Haruya Meren; France Varin; Mary Ruwart; Ronald G. Thurman


Publisher
John Wiley and Sons
Year
1986
Tongue
English
Weight
495 KB
Volume
6
Category
Article
ISSN
0270-9139

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✦ Synopsis


Previous work demonstrated that collagen deposition in the liver of rats fed a nutritionally deficient diet for 3 to 4 months was diminished markedly by 16,16-dimethyl prostaglandin Ef treatment. In this study, rats were fed a high-fat diet or a high-fat diet deficient in lipotropem for 2 to 4 weeks prior to liver perfusion. Rates of 0, uptake by the liver were not changed by dietary manipulation. Infusion of 16,16-dimethyl prostaglandin Ez (10 &, however, decreased O2 uptake by the whole organ by 20 to 40% in both groups. 0, tension was measured at the liver surface with a miniature O2 electrode placed alternatively on periportal and pericentral regions of the liver lobule. Mean 0, tensions in both periportal and pericentral regions were reduced 2-to 3fold during the infusion of 16,16-dimethyl prostaglandin Ez suggesting an action on the microcirculation. This hypothesis was supported by the observation that fluorescein isothiocyanate-dextran fluorescence detected from the liver surface as well as hepatic vascular volume determined by dye dilution techniques were decreased 30 to 50% by 16,16-dimethyl prostaglandin Ez. In addition, 16,16-dimethyl prostaglandin Ez increased portal pressure by about 10 mm Hg in a reversible manner. Thus, it is concluded that pharmacological levels of 16,ls-dimethyl Prostaglandin Ez affects the microcirculation dramatically in the isolated perfused liver.

When rats are fed a diet rich in fats and deficient in liptropes for 3 to 4 months, a fatty liver with collagen deposits develops (1). Recently, Ruwart et al. (2) showed that concomitant treatment of rats with daily subcutaneous injections of 16,16-dimethyl prostaglandin E2 (DMPGE2) for 4 months diminished the accumulation of fat and delayed the fibrogenesis due to the lipotropedeficient dietary treatment. Furthermore, it was also shown that DMPGE2 (100 pg per kg) could halt the progression of established fibrosis in this model (2). Similarly, Angaard and his colleagues (3) have shown that accumulation of fat secondary to chronic dietary


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