DOSE-RESPONSE PROFILES OF HUMAN GROWTH-HORMONE IN SUBCUTANEOUS WOUND CHAMBERS IN RATS

Objective: To investigate dose response profiles of human growth hormo ne in soft connective tissue healing when it is given locally in subcu taneous wound chambers. Design: Placebo controlled parallel study. Set ting: Institute of Medical Anatomy, Denmark. Material: 36 male Sprague Dawley rats, in three group of 12. Interventions: Stainless steel wir e mesh cylinders 7 mm in diameter and 20 mm long were implanted subcut aneously in pairs in the upper and lower back on either side of the mi dline in three groups of male Sprague Dawley rats. Two groups were eac h 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 th e two cylinders on the opposite side. Group 3 were given vehicle alone in two cylinders and needle puncture (sham) on the opposite side. Inj ections of growth hormone or vehicle (placebo) were given every three days for 16 days. Main outcome measures: Body weight, weight of granul ation tissue, and concentrations of hydroxyproline and aminoterminal p ropeptide of procollagen type III.Results: The dose response curves fo r weight of granulation tissue and deposition of collagen were upward convex (ANOVA p < 0.001 and 0.001, respectively). Growth hormone in do ses of 0.2 and 0.7 IU stimulated formation of granulation tissue to me ans of 180% (95% confidence interval (CI) 149% to 210%) and 174% respe ctively). 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% CI 137% to 177%) more granulation tissue than the cylinders in group 3 , indicating that locally applied growth hormone also had a systemic e ffect. Conclusion: The clinical use of topical growth hormone in wound healing may be complicated by the relatively narrow therapeutic inter val.