Dose response profiles of human growth hormone in subcutaneous wound chambers in rats.
OBJECTIVE
To investigate dose response profiles of human growth hormone in soft connective tissue healing when it is given locally in subcutaneous wound chambers.


METHODS
Placebo controlled parallel study.


METHODS
Institute of Medical Anatomy, Denmark.


METHODS
36 male Sprague Dawley rats, in three group of 12.


METHODS
Stainless steel wire mesh cylinders 7 mm in diameter and 20 mm long were implanted subcutaneously in pairs in the upper and lower back on either side of the midline in three groups of male Sprague Dawley rats. Two groups were each given two different doses of growth hormone (group 1, 0.2 and 0.7 IU; and group 2, 0.02 and 2 IU) in two cylinders and vehicle alone in the two cylinders on the opposite side. Group 3 were given vehicle alone in two cylinders and needle puncture (sham) on the opposite side. Injections of growth hormone or vehicle (placebo) were given every three days for 16 days.


METHODS
Body weight, weight of granulation tissue, and concentrations of hydroxyproline and aminoterminal propeptide of procollagen type III.


RESULTS
The dose response curves for weight of granulation tissue and deposition of collagen were upward convex (ANOVA p < 0.001 and 0.001, respectively). Growth hormone in doses of 0.2 and 0.7 IU stimulated formation of granulation tissue to means of 180% (95% confidence interval (Cl) 149% to 210%) and 174% (95% Cl 148% to 200%) more than in the placebo treated cylinders (group 3) (p < 0.05 and < 0.01, respectively). Doses of 0.2 and 2 IU, however, had less effect. The placebo cylinders in animals in groups 1 and 2 contained a mean of 157% (95% Cl 137% to 177%) more granulation tissue than the cylinders in group 3, indicating that locally applied growth hormone also had a systemic effect.


CONCLUSIONS
The clinical use of topical growth hormone in wound healing may be complicated by the relatively narrow therapeutic interval.
Rasmussen
L H
LH
Dept. of Surgery, Herlev Hospital, Copenhagen, Denmark.
Garbarsch
C
C
Schuppan
D
D
Moe
D
D
Hørslev-Pedersen
K
K
Gottrup
F
F
Steenfos
H
H
D000818:Animals; D001835:Body Weight; D003094:Collagen / Q000378:metabolism; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006097:Granulation Tissue / Q000187:drug effects / Q000378:metabolism; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D019382:Human Growth Hormone; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D009929:Organ Size; D010446:Peptide Fragments / Q000097:blood; D010919:Placebos; D011347:Procollagen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013193:Stainless Steel; D013526:Surgical Mesh; D014945:Wound Healing / Q000187:drug effects
D010446:Peptide Fragments; D010919:Placebos; D011347:Procollagen; D011994:Recombinant Proteins; C041876:procollagen Type III-N-terminal peptide; D013193:Stainless Steel; D019382:Human Growth Hormone; D013006:Growth Hormone; D003094:Collagen; D006909:Hydroxyproline