Some Agents Which Potentiate the Inotropic Response of the Papillary Muscle to Epinephrinel

T HE CURRENT STUDY was suggested by the observation that various substances are capable of potentiating the inotropic response of the papillary muscle to epinephrine. The object of the study has been to obtain information about the nature of the action by which such substances as cysteine, cystine, tyrosine, ascorbic acid, and plasma are capable of producing this potentiation. Four possible sites of action are considered where such substances might act to alter the response of the papillary muscle to epinephrine. These are: a) the tissue enzymes involved in the destruction of epinephrine; b) the autoxidation of epinephrine; c) the sensitivity of the muscle to epinephrine; d) the general responsiveness of the muscle. Several different tissue enzymes which destroy epinephrine have been considered in the literature. Blaschko et al. (I) demonstrated that tissues contain a cyanide-insensitive enzyme, amine oxidase, which inactivates epinephrine. Clark and Raventos (2) concluded that the isolated frog auricle will oxidize epinephrine by means of a tissue catalyst. However, these authors did not study the auricle in a bath, but instead, moistened it by topical application with the epinephrine solution. Green and Richter (3) have shown that the cytochrome-indophenol-oxidase system present in all tissues will catalyze the oxidation of epinephrine to adrenochrome This cytochrome-oxidase system is found in especially high concentrations in cardiac muscle. Inactivation of these enzyme systems should potentiate the action of epinephrine. The fact that numerous agents inhibit the autoxidation of epinephrine by molecular oxygen in vitro is well known. Such inhibition