The nature of the positive inotropic response of the isolated frog heart to theophylline and to iminazole

Abstract

1. The mechanism of the positive inotropic responses to theophylline and to iminazole has been examined in the frog heart.2. Both theophylline and iminazole caused positive inotropic effects which declined to control amplitude with time despite continued exposure to the drugs. The duration of the response to iminazole was always longer than that to theophylline.3. On washout of theophylline and iminazole the amplitude of heart beat slowly decreased to a value below that in the control period.4. The theophylline response was not prevented by phentolamine or by propranolol given separately or in combination.5. Theophylline potentiated the staircase and prolonged the post-stimulation potentiation phenomena when its own inotropic activity had subsided but iminazole reduced the staircase effect at this time.6. Theophylline, iminazole and 3 x [Ca(2+)](o) all increased the influx of (45)Ca into isolated ventricles. Theophylline increased but iminazole and 3 x [Ca(2+)](o) slightly reduced (45)Ca efflux.7. Total cell calcium changes were only detected in ventricles exposed for 15 min to 3 x [Ca(2+)](o) or theophylline (5 x 10(-3)M). After 60 min exposure to theophylline the total cell calcium was not significantly different from controls.8. It is concluded that the positive inotropic responses to theophylline and iminazole can be interpreted in terms of the increased calcium influx which they produce and that interpretation of effects in terms of their action on phosphodiesterase should be treated with reservation.