The effect of hypoxia and acidosis on propranolol clearance in the isolated perfused rat liver preparation

The effect of hypoxia and acidosis on the elimination of an oxidatively metabolized drug, S-propranolol, was examined in the single-pass isolated perfused rat liver (IPRL). The experiments (N = 6) consisted of four consecutive 30 min phases: normal pH (pH 7.4)/normal oxygen delivery, normal pH/hypoxia, hypercapnic acidosis (pH 7.1)/normal oxygenation and hypercapnic acidosis/ hypoxia. Hypoxia and acidosis were produced by equilibrating the perfusate with appropriate mixtures of O₂, N₂ and CO₂. With normal oxygen delivery there was no difference in hepatic clearance of propranolol between normal pH and acidosis (9.65 ± 0.34 and 9.78 ± 0.11 mL/min, respectively. P < 0.05). During hypoxia, propranolol clearance was impaired to a similar extent under both pH conditions (7.41 ± 0.97 and 8.06 ± 0.81 mL/min, respectively, P > 0.05). Therefore, respiratory acidosis does not affect the clearance of propranolol by the IPRL, nor does it influence the sensitivity of propranolol clearance to hypoxia. Neither acidosis nor hypoxia resulted in a significant reduction in bile flow compared with the normal pH/normal oxygen phase and there was no correlation between bile flow and perfusate bicarbonate concentration (P > 0.05).