Time dependent effects of adriamycin and x-ray therapy on wound healing in the rat

Wound healing as measured by wound breaking strength (WBS) was studied in male Fischer rats. Animals were wounded (day 0) and treated with Adriamycin (ADR), x-ray therapy (XRT), or the combination of ADR + XRT. Treatments were either on day -7,0 or +7. Animals were killed on days +14 and +21, and excised wounds were subjected to uniaxial extension and the recording of WBS (grams), hydroxy-proline assay, and collagen fiber diameter measurements. Day 0 treatment yielded WBS averaging 46% (ADR), 41% (XRT), and 26% (ADR + XRT) of control by 21 days. Newly synthesized hydroxyproline (scar collagen) values of day 0 treated animals were 47% (ADR), 66% (XRT), and 39% (ADR + XRT) of control at 21 days. Day -7 treatment yielded similar WBS values. Withholding single agent or combined treatment until day +7 yielded WBS values comparable to control at 14 or 21 days. In this model, day 0 treatment with ADR, XRT, or ADR + XRT impaired WBS most significantly. This was supported by a diminution in newly synthesized hydroxyproline and load extension curve analysis.