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.

DESIGN

Placebo controlled parallel study.

SETTING

Institute of Medical Anatomy, Denmark.

MATERIAL

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

INTERVENTIONS

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.

MAIN OUTCOME MEASURES

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.

CONCLUSION

The clinical use of topical growth hormone in wound healing may be complicated by the relatively narrow therapeutic interval.