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Adenine Nucleotides and Carbohydrates in Subpopulations of Hepatic Nodules with Normal and Compromised Microcirculation¹

Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27514 [I. A., J. M. t. K., H. Y., R. G. T.]; the Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey [F. C. K., M. W.]; and the Department of Experimental Pathology and Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709 [J. A. P.]

Fluorescein-isothiocyanate dextran (FITC-dextran), a dye confined to the vascular space, was infused via the hepatic artery and portal vein into perfused livers from fed rats treated with diethylnitrosamine for 4 to 5 months. Fluorescence due to FITC-dextran was detected with fiberoptic microlight guides placed on surface nodules of about 5 mm in diameter. Nodules were categorized into groups with normal and compromised microcirculation based on their fluorescence following infusion of FITC-dextran. Similar results were obtained when nodules were classified based on reflectance of trypan blue. Despite compromised microcirculation, ATP and ADP levels as well as ATP/ADP ratios were comparable in both groups of nodules; however, AMP was elevated in FITC-dextran-negative nodules (i.e., those with compromised microcirculation). Nodules with compromised microcirculation also contained higher glucose and lactate levels than nodules that were well perfused; however, glycogen was five times lower than in FITC-dextran-positive nodules. Fasting reduced ATP/ADP ratios in poorly perfused nodules in comparison to well-perfused nodules. In perfused livers from fed rats where glycogen was high, however, ATP/ADP ratios and rates of ATP depletion during ischemia were the same in well-perfused and poorly perfused nodules. Products of glycogen breakdown (e.g., glucose and lactate) were elevated in nodules from livers of fed but not fasted rats. The results indicate that alteration of perfusion of hepatic nodules does not change ATP levels nor the capacity of nodules to utilize high energy phosphate during anoxia. Thus, near normal energy status is maintained from glycogen metabolism in poorly perfused nodules via glycolysis. Since basal ATP content and utilization is comparable in well and poorly perfused nodules, compromised energy status is unlikely to explain selection of nodules that regress to near normal hepatocytes.

¹ Supported, in part, by Grant ES-02759 from NIEHS and Grants CA-23080 and CA-20807 from the National Cancer Institute, as well as by a fellowship from the Netherlands Organization for Scientific Research.

² To whom requests for reprints should be addressed, at Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, CB 7365, FLOB, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514.

Received 12/29/88. Revised 3/16/89. Accepted 3/22/89.

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