Growth hormone secretagogue increases muscle strength during remobilization after canine hindlimb immobilization.
Twenty-two beagles were divided into two equal groups, and the right hindlimb of each animal was immobilized at 105 degrees of knee flexion by external fixation. After 10 weeks of fixation, the device was removed, allowing free mobility for the following 5 weeks. Each day throughout the 15 weeks, one group received a growth hormone secretagogue (treatment) at a dose of 5 mg/kg, and the other received a lactose placebo (control). At weeks 0, 10, and 15, strength as indicated by maximum isometric extension torque was measured in the right hindlimb, biopsies of the vastus lateralis muscle were taken, and the dogs were weighed. Weekly blood samples were analyzed for insulin-like growth factor-1, blood urea nitrogen, and creatine phosphokinase. Between weeks 0 and 10, tetanic torque declined by about 60% (p < 0.001) in both groups, with no significant difference between the groups (p > 0.7). Between weeks 10 and 15, tetanic torque in the treated group increased by 0.81 Nm; this was significantly greater than the increase of 0.25 Nm in the placebo group (p < 0.05). The diameters of slow (type-1) and fast (type-2) fibers measured from the vastus lateralis muscle followed the same trend. At all time points, fiber diameter correlated strongly with torque; this argues against nonmuscular causes such as nerve injury for strength loss. The mean levels of insulin-like growth factor-1 increased 100% by week 4 in the treated group and remained elevated by about 60% throughout the experiment. Levels of insulin-like growth factor-1 in the placebo group decreased 30% within week 1 and remained depressed throughout the experiment. Our interpretation of these data suggests that the growth hormone secretagogue elevated levels of serum insulin-like growth factor-1, which in turn increased the size and strength of the quadriceps muscle during remobilization. These data may ultimately have therapeutic application to humans during rehabilitation after prolonged inactivity.
Lieber
R L
RL
Department of Orthopaedics and Bioengineering, University of California and Veterans Administration Medical Centers, San Diego 92161, USA. rlieber@ucsd.edu
Jacks
T M
TM
Mohler
R L
RL
Schleim
K
K
Haven
M
M
Cuizon
D
D
Gershuni
D H
DH
Lopez
M A
MA
Hora
D
D
Nargund
R
R
Feeney
W
W
Hickey
G J
GJ
D000818:Animals; D001284:Atrophy; D004285:Dogs; D016267:External Fixators; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006614:Hindlimb; D007103:Immobilization / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology*; D010919:Placebos; D013141:Spiro Compounds / Q000494:pharmacology*; D019415:Torque
D010880:Piperidines; D010919:Placebos; D013141:Spiro Compounds; C102119:L 163255; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone