Abstract
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 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 (< 50 Hz), caffeine (1 and 5 mM) augmented the tension generated by fresh muscle in response to phrenic nerve and direct stimulation in a dose-dependent fashion. At high stimulus frequencies (> 50 Hz), 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. Caffeine augmented tension production in fresh and fatigued diaphragmatic muscle by a direct effect on the processes that activated contraction and this effect was greatest when the muscle was minimally activated (low stimulus frequencies). Caffeine may have adversely affected muscle tension by impairing neuromuscular transmission.