RT Journal Article
SR Electronic
T1 Effects of fasting induced carbohydrate depletion on murine ischemic skeletal muscle function
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 846774
DO 10.1101/846774
A1 Cameron A. Schmidt
A1 Emma J. Goldberg
A1 Tom D. Green
A1 Reema R. Karnekar
A1 Jeffrey J. Brault
A1 Spencer G. Miller
A1 Adam J. Amorese
A1 Dean J. Yamaguchi
A1 Espen E. Spangenburg
A1 Joseph M. McClung
YR 2019
UL http://biorxiv.org/content/early/2019/11/18/846774.abstract
AB Stored muscle carbohydrate supply and energetic efficiency constrain muscle functional capacity during exercise and are influenced by common physiological variables (e.g. age, diet, and physical activity level). Whether these constraints affect overall functional capacity or the timing of muscle energetic failure during acute ischemia is not known. We interrogated skeletal muscle contractile properties in two anatomically distinct hindlimb muscles that have well characterized differences in energetic efficiency (locomotory-extensor digitorum longus (EDL) and postural-soleus muscles) under conditions of reduced carbohydrate supply. 180 mins of acute ischemia resulted in complete energetic failure in all muscles tested, indicated by: loss of force production, substantial reductions in total adenosine nucleotide pool intermediates, and increased adenosine nucleotide degradation product - inosine monophosphate (IMP). These changes occurred in the absence of apparent myofiber structural damage assessed histologically by both transverse section and whole mount. Restriction of the available intracellular carbohydrate pool by fasting (~50% decrease in skeletal muscle) did not significantly alter the timing to muscle functional impairment or affect the overall force/work capacities of either muscle type. Fasting did cause rapid development of passive tension in both muscle types, which may have implications for optimal timing of reperfusion or administration of precision therapeutics.