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

Abstract

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 O 2, N 2 and CO 2. 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).