Am. J. Respir. Crit. Care Med., Vol 149, No. 4, 04 1994, 920-924.
Inotropic effects of theophylline on foreshortened canine diaphragm
G Gayan-Ramirez and M Decramer
Respiratory Muscle Research Unit, Laboratory of Pneumology, Katholieke Universiteit Leuven, Belgium.
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.
