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 placed at optimal length (Lo) and 70% Lo were compared. At Lo, compared with time-matched control, Pt significantly increased after theophylline (e.g., 37 +/- 32 versus -8 +/- 12% after 400 mg/L) except with 20 mg/L. At 70% Lo, Pt increased with all theophylline concentrations 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 theophylline both at Lo and 70% Lo. In addition, for a given concentration, twitch potentiation was significantly greater at 70% Lo than at Lo, the difference increasing with increasing concentration (e.g., 3 times greater with 400 mg/L). We conclude that theophylline-induced inotropic effects on Pt were more pronounced on foreshortened canine diaphragm bundles than on bundles placed at Lo. These observations confirm that theophylline-induced inotropic effects on foreshortened muscle previously observed in vivo are likely to result from a direct effect on muscle contractility.