Effect of hypoxia and pregnancy on antipyrine metabolism in isolated perfused rat livers.

The effect of hypoxia on antipyrine metabolism was studied in isolated perfused livers from pregnant (19-21 days gestation) and nonpregnant female Wistar rats. Hypoxia was induced by altering the blood content and/or flow rate of the recirculating perfusion medium. Inflow and outflow pO2 values, in themselves, were not valid indicators of oxygen delivery and consumption when the liver was perfused with a blood containing medium. At a given oxygen delivery rate, oxygen consumption per gram of liver was the same in nonpregnant and pregnant rat livers. The absolute clearance of antipyrine (milliliters per hour) was significantly greater in livers from pregnant compared to nonpregnant rats, whereas antipyrine clearance, corrected for liver weight (milliliters per hour gram of liver), was significantly lower in pregnant rat livers. Antipyrine clearance (milliliters per hour) was linearly related to oxygen consumption (milliliters per minute or micromoles per minute per gram of liver) in both the nonpregnant and pregnant rat livers. As oxygen consumption decreased, livers from pregnant rats maintained a greater ability to clear antipyrine than livers from nonpregnant rats. This study emphasizes the importance of maintaining adequate oxygen delivery to isolated perfused livers during drug metabolism studies to ensure constant oxygen consumption. Otherwise, alterations in the flow rate or hematocrit of the perfusion medium may directly alter the elimination rate of the substrate.