Contribution of No-reflow phenomenon to hepatic injury after ischemia-reperfusion: Evidence for a role for superoxide anion

Authors

  • Anthony Koo M.D., Ph.D.,

    Corresponding author
    1. Department of Medicine, University of Southern California School of Medicine, Los Angeles, California 90033
    • Department of Medicine, Division of Gastrointestinal and Liver Diseases, University of Southern California School of Medicine, 1333 San Pablo Street, MMR ± 415, Los Angeles, CA 90033
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  • Hirokazu Komatsu,

    1. Department of Medicine, University of Southern California School of Medicine, Los Angeles, California 90033
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  • Gongming Tao,

    1. Department of Medicine, University of Southern California School of Medicine, Los Angeles, California 90033
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  • Masayashu Inoue,

    1. Department of Biochemistry, Kumamoto University Medical School, Kumamoto, Japan
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  • Paul H. Guth,

    1. Center for Ulcer Research and Education, University of California Los Angeles, School of Medicine, and Veterans Administration Medical Center, West Los Angeles, Los Angeles, California 90073
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  • Neil Kaplowitz

    1. Department of Medicine, University of Southern California School of Medicine, Los Angeles, California 90033
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Abstract

Controversy exists as to the role of oxygen-derived free radicals in tissue injury and the no-reflow phenomenon in reperfusion injury after ischemia. In this study using an experimental rat model, left hepatic lobar ischemia followed by reperfusion resulted in an increase of serum glutamic pyruvic transaminase at 30 min with concomitant histological evidence of hepatocellular necrosis at 24 hr. In the in vivo liver microcirculation, reperfusion after ischemia resulted in an initial transient return of blood flow, but stasis of blood flow later developed in the liver sinusoids. Thus a no-reflow phenomenon in the microcirculation was demonstrated. Intravenous administration of a longacting form of superoxide dismutase (half-life 6 hr, dose 4 or 8 mg/kg) significantly decreased the hepatocellular necrosis and reduced the microcirculatory stasis in the liver sinusoids. These studies established the important contribution of the no-reflow phenomenon in ischemia-reperfusion injury to the liver and the participation of superoxide anions in mediating the no-reflow phenomenon.

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