The effect of MET-88 (3-(2,2,2-trimethylhydrazinium) propionate dihydrate), a gamma-butyrobetaine (gamma-BB) hydroxylase inhibitor, on the hydrogen peroxide (H2O2)-induced mechanical and metabolic derangements was studied in the isolated rat heart, which was perfused aerobically by the Langendorff's technique at a constant flow rate and driven electrically. In the first series of experiments, MET-88 (100 mg/kg/d) was orally administered to rats for 10 days prior to isolation of the heart. In the second series of experiments, MET-88 or gamma-BB was directly infused to the isolated perfused heart. In both series of experiments, H2O2 (600 microM) decreased the left ventricular developed pressure (mechanical dysfunction) and the tissue levels of high-energy phosphates (metabolic derangement). In the first series of experiments, oral pretreatment with MET-88 attenuated the H2O2-induced metabolic derangement with a marked increase in the myocardial level of gamma-BB, while it did not attenuate the H2O2-induced mechanical dysfunction. In the second series of experiments, MET-88 (1 mM) did not attenuate the H2O2-induced metabolic derangement, whereas gamma-BB (500 microM or 1 mM) attenuated it. Nevertheless, gamma-BB did not modify the energy metabolism of H2O2-untreated heart (normal heart). These results suggest that oral pretreatment with MET-88 protects the energy metabolism against the H2O2-induced derangement and that the beneficial effect of the oral pretreatment with MET-88 may be mediated by gamma-BB that has accumulated in the myocardium because of inhibition of gamma-BB hydroxylase.