Differential Effects of BDF 9148 and DPI 201–106 on Action Potential and Contractility in Rat and Guinea Pig Myocardium

The effects of BDF 9148 and its parent compound DPI 201-106 were compared in guinea pigs and rat cardiac tissue because these tissues possess long and short action potentials (AP), respectively, and have different excitation-contraction coupling mechanisms. Conventional electrophysiologic techniques were used to study drug effects on AP, sodium current, and force of contraction (Fc). In guinea pig and rat papillary muscle, BDF 9148 and DPI 201-106 increased Fc; BDF 9148 was more potent than DPI 201-106. In guinea pig, but not in rat muscle, DPI 201-106 significantly prolonged AP duration (APD) to a greater degree than did BDF 9148. In rat cardiac muscle, both agents were more potent but increased Fc to a lesser degree than in guinea pig cardiac muscle and led to Ca2+ overload, as evidenced by after-contractions and contracture. BDF 9148 failed to increase Fc at low frequencies in guinea pig but was effective at all frequencies in rat muscle. In isolated myocytes, substance effects on sodium current were similar in both species. In guinea pigs, but not in rats, DPI 201-106 prolongs APD to a greater degree than does BDF 9148. Both agents produce a greater positive inotropic effect in guinea pigs than in rats, which may be due to species differences in excitation-contraction coupling.