INOTROPIC EFFECTS OF THEOPHYLLINE ON FORESHORTENED CANINE DIAPHRAGM

We previously demonstrated that theophylline exerted greater inotropic effects on foreshortened canine diaphragm than on diaphragm placed at resting length in vivo (1). To ensure that these effects result from an effect on the muscle itself, they were examined in vitro. Thus, the effects of increasing doses of theophylline (20, 100, 200, and 400 mg /L) or addition of Krebs solution on twitch tension (Pt) of bundles pl aced at optimal length (L(0)) and 70% L(0) were compared. At L(0), com pared with time-matched control, Pt significantly increased after theo phylline (e.g., 37 +/- 32 versus -8 +/- 12% after 400 mg/L) except wit h 20 mg/L. At 70% L(0), Pt increased with all theophylline concentrati ons in a dose-related manner (e.g, 14 +/- 15 versus -6 +/- 7% and 114 +/- 57 versus -8 +/- 11% after 20 and 400 mg/L, respectively). Time to peak tension and half-relaxation time remained unchanged after theoph ylline both at L(0) and 70% L(0). In addition, for a given concentrati on, twitch potentiation was significantly greater at 70% L(0) than at L(0), the difference increasing with increasing concentration (e.g., 3 times greater with 400 mg/L). We conclude that theophylline-induced i notropic effects on Pt were more pronounced on foreshortened canine di aphragm bundles than on bundles placed at L(0). These observations con firm that theophylline-induced inotropic effects on foreshortened musc le previously observed in vivo are likely to result from a direct effe ct on muscle contractility.