INHIBITION OF WOUND CONTRACTION WITH COLCHICINE AND D-PENICILLAMINE

The effects of locally injected combined colchicine and D-penicillamin e on wound contraction were investigated in a murine model. Two full-t hickness excisional wounds were made on either side of the back of hai rless (hr/hr) mice. A volume of 0.15 ml of colchicine, D-penicillamine , or combined colchicine and D-penicillamine in normal saline vehicle were injected daily into the wound on one side of the animal and 0.15 ml of vehicle alone was injected into the wound on the other side for 5 or 10 days; thus, each animal served as its own control. The surface area of each wound was measured on Days 0, 5, and 10 to determine an index of the rate of wound contraction. At the end of the experimental period (Day 5 or 10), wounds were excised en bloc from euthanized ani mals for histological studies. The following histological parameters w ere determined: the thickness of the granulation tissue, the number of fibroblasts in granulation tissue per unit area, and the number of in flammatory cells (neutrophils, lymphocytes, macrophages, mast cells) i n subjacent muscle per unit area, Our data showed that after 5 days of treatment, wound contraction was significantly inhibited only in woun ds treated with combined colchicine and D-penicillamine. Wound contrac tion was significantly inhibited even after 10 days of treatment with the combination. Histological studies revealed that although the thick ness of the granulation tissue and the number of inflammatory cells in subjacent muscle were decreased by D-penicillamine alone, only combin ed colchicine and D-penicillamine decreased the thickness of the granu lation tissue, fibroblasts in granulation tissue, and inflammatory cel ls in subjacent muscle, Our data suggests that very low concentrations of colchicine and D-penicillamine when combined and injected locally may be potentially useful in controlling surface scar formation. (C) 1 996 Academic Press, Inc.