Caffeine administration results in greater tension development in previously fatigued canine muscle in situ

In isolated single skeletal myocytes undergoing long‐term fatiguing contractions, caffeine (CAF) can result in nearly immediate restoration of generated tension to near‐prefatigue levels by increasing Ca 2+ release via activation of sarcoplasmic reticulum release channels. This study tested whether arterial CAF infusion (>5 m m ) would cause a similar rapid restoration of tetanic isometric tension during contractions to fatigue in perfused canine hindlimb muscle in situ . Tetanic contractions were elicited by electrical stimulation (200 ms trains, 50 Hz, 1 contraction s −1 ), and biopsies were taken from the muscle at rest and during contractions: (1) following the onset of fatigue (tension ∼60% of initial value); and (2) following CAF administration. Resting muscle ATP, PCr and lactate contents were 25.2 ± 0.4, 76.9 ± 3.3 and 14.4 ± 3.3 mmol (kg dry weight) −1 , respectively. At fatigue, generated tetanic tension was 61.1 ± 6.9% of initial contractions. There was a small but statistically significant recovery of tetanic tension (64.9 ± 6.6% of initial value) with CAF infusion, after which the muscle showed incomplete relaxation. At fatigue, muscle ATP and PCr contents had fallen significantly ( P < 0.05) to 18.1 ± 1.1 and 18.9 ± 2.1 mmol (kg dry weight) −1 , respectively, and lactate content had increased significantly to 27.7 ± 5.4 mmol (kg dry weight) −1 . Following CAF, skeletal muscle ATP and PCr contents were significantly lower than corresponding fatigue values (15.0 ± 1.3 and 10.9 ± 2.2 mmol (kg dry weight) −1 , respectively), while lactate was unchanged (22.2 ± 3.9 mmol (kg dry weight) −1 ). These results demonstrate that caffeine can result in a small, but statistically significant, recovery of isometric tension in fatigued canine hindlimb muscle in situ , although not nearly to the same degree as seen in isolated single muscle fibres. This suggests that, in this in situ isolated whole muscle model, alteration of Ca 2+ metabolism is probably only one cause of fatigue.