title: Caffeine administration results in greater tension development in previously fatigued canine muscle in situ.
abstract: 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 Ca2+ release via activation of sarcoplasmic reticulum release channels. This study tested whether arterial CAF infusion (>5 mm) 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 approximately 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 Ca2+ metabolism is probably only one cause of fatigue.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0623, USA. rhowlett@ucsd.edu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Howlett
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Kelley
authors.forename: Bruno
authors.initials: B
authors.lastname: Grassi
authors.forename: L Bruce
authors.initials: LB
authors.lastname: Gladden
authors.forename: Michael C
authors.initials: MC
authors.lastname: Hogan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D006614:Hindlimb; D019344:Lactic Acid / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D018763:Muscle Fatigue / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D010725:Phosphocreatine / Q000378:metabolism; D012584:Sciatic Nerve / Q000502:physiology
chemical_list: D010725:Phosphocreatine; D019344:Lactic Acid; D002110:Caffeine; D000255:Adenosine Triphosphate