Elimination but not accumulation of metoprolol by rat isolated perfused heart is selectively impaired by hypoxia

Abstract

1. The influence of hypoxia on the time course of regional myocardial accumulation and elimination of the beta 1-adrenoceptor antagonist metoprolol was investigated by a spontaneously beating rat isolated perfused heart preparation. 2. Myocardial metoprolol content was maximal at 2 min in the left and right ventricles and atria. Neither the extent nor the time of maximal myocardial metoprolol content was significantly influenced by the induction of hypoxia. However, maximal myocardial metoprolol content in both atria and right ventricles was significantly higher than that in the left ventricular samples (P < 0.02; one-factor analysis of variance, 17 d.f.). 3. Elimination of metoprolol (as indicated from residual myocardial metoprolol content at 10 min) was impaired in hypoxic left ventricles (P < 0.01 vs normoxia; unpaired t-test, 10 d.f.) but not in right ventricles or atria. This variation in myocardial metoprolol disposition was not apparent from examination of serial metoprolol concentrations in coronary perfusate. 4. Hypoxia selectively impaired the elimination of metoprolol from the left ventricle, but not the process of drug accumulation, by any region of myocardium. It remains to be determined whether this reflects regional variation in the extent of microcirculatory impairment associated with hypoxia.