Fatigue in frog skeletal muscle fibres and effects of methylxanthine derivatives.

The influence of theophylline and the related drug caffeine on the mechanical performance of fatigued muscle fibre isolated from semitendinosus muscle of Rana temporaria (2.5-6.7 degrees C) was investigated. The fibre was stimulated supramaximally to produce I s fused tetani and 2 s and 10 s partially fused tetani at intervals of 10 min. Fatigue was produced by shortening the contraction interval to 15 and 30 s. This caused a 15-20% decline in the maximum tension during fused tetanus and a 40-50% decline during partially fused tetanus. Theophylline and caffeine (0.1-0.5 mM) did not change the maximum tension developed by the fatigued fibre during fused tetanization. Both drugs, however, markedly increased the tension output of the fatigued muscle fibre during partially fused tetanus. It was observed that the increase in partially fused tetanic tension by theophylline and caffeine was associated with an increase in the degree of fusion. This later effect was even more pronounced in the presence of diethyl-stilboestrol. It is concluded that these drugs may not reverse the metabolic changes caused by fatigue, since they are unnable to increase fused tetanic force of a fatigued muscle fibre. The increase in partially fused tetanic tension of a fatigued muscle fibre by these drugs is probably due to enhancement of the activator calcium release from the sarcoplasmic reticulum in response to stimulation.