COMPARISON OF EFFECT OF CARBON-MONOXIDE AND OF HYPOXIC HYPOXIA .2. HEXOBARBITAL METABOLISM IN ISOLATED, PERFUSED RAT-LIVER

  • 1 January 1976
    • journal article
    • research article
    • Vol. 199  (1) , 61-66
Abstract
Rat livers were perfused with a red blood cell-containing perfusion medium. The rate of metabolism of hexobarbital was determined in this system as the recirculating perfusion fluid was made hypoxic by exposure to either CO or lowered O2 tension. Of the total O2 consumed by the liver 7.6% was utilized to metabolize hexobarbital [hex] regardless of the severity of the hypoxia, which suggests that the liver does not shunt O2 to more preferential pathways as O2 availability becomes limited. When O2 delivery was lowered below 0.3 ml of O2 per min/g of liver by either type of hypoxia, the rate of hex metabolism decreased. Based on the rate of O2 delivery, CO was more potent than hypoxic hypoxia inhibiting drug metabolism. The 2 types of hypoxia were equipotent when compared on the basis of alterations in O2 consumption. These results are consistent with the known effect of CO in decreasing the availability of Hb bound O2 and argue against the direct inhibition of drug metabolism by the binding of CO to cytochrome P-450 in the isolated liver. The lack of a greater potency of CO relative to hypoxic hypoxia in vivo might be related to alterations in hepatic blood flow.

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