The effect of caffeine on diaphragmatic muscle force in normal hamsters

The effect of caffeine on the tension generated by fresh and fatigued diaphragmatic muscle was examined in 32 Syrian hamsters. Studies were performed in vitro on innervated diaphragmatic muscle strips activated by electrical stimuli applied either directly or via the phrenic nerve. The degree of activation of the muscle was varied by altering the frequency of stimulation. When the stimulus frequency was low (less than 50 Hz), caffeine (1 mM and 5 mM) augmented the tension generated by fresh muscle in response to both phrenic nerve and direct stimulation in a dose-dependent fashion. At high stimulus frequencies (greater than 50 Hz), however, the response to caffeine was different in directly activated and phrenic-nerve-activated muscles. Caffeine augmented tension production at all stimulus frequencies in directly activated muscles, but decreased the tension developed in response to phrenic stimulation. The increase in tension elicited by caffeine during direct stimulation was relatively smaller at high compared with at low stimulus frequencies. Caffeine augmented peak tension by increasing the rate of tension development and prolonging the period during which tension increased. Similar effects were observed in muscle strips fatigued by prolonged activity. We conclude that caffeine augments tension production in both fresh and fatigued diaphragmatic muscle by a direct effect on the processes that activate contraction and that this effect is greatest when the muscle is minimally activated (low stimulus frequencies). Caffeine, however, may adversely affect muscle tension by impairing neuromuscular transmission.