A collagen prolyl 4-hydroxylase inhibitor reduces adhesions after tendon injury.
Collagen synthesis inhibition potentially can reduce adhesion formation after tendon injury but also may affect cutaneous wound healing. We hypothesized that a novel orally administered collagen synthesis inhibitor (CPHI-I) would substantially reduce flexor tendon adhesions after injury, without any clinically important effect on cutaneous wound healing. The experiments were performed in a rat model with an in-continuity crush injury model in the rat hindfoot flexor tendon to provoke adhesion formation. Assays of dermal collagen production and the rate of healing of an excised wound were performed to assess cutaneous wound healing. Animals in the treatment groups received CPHI-I for 1, 2, or 6 weeks and were assessed at either 2 or 6 weeks. The work of flexion in the injured digit was reduced in the CPHI-I-treated animals compared with control animals, (0.188 J versus 0.0307 J at 2 weeks, and 0.0231 J versus 0.0331 J at 6 weeks) The cutaneous wound healing rate was similar in all animals, but dermal collagen synthesis was reduced in the treated animals. The CPHI-I seems to reduce tendon adhesion, and although collagen synthesis was reduced in cutaneous wounds, CPHI-I did not retard wound healing.
McCombe
D
D
Bernard O'Brien Institute of Microsurgery, St Vincent's Hospital, University of Melbourne, Melbourne, Australia. mccombdb@svhm.org.au
Kubicki
M
M
Witschi
C
C
Williams
J
J
Thompson
E W
EW
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003094:Collagen / Q000096:biosynthesis*; D004195:Disease Models, Animal; D008297:Male; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013708:Tendon Injuries / Q000150:complications*; D000267:Tissue Adhesions / Q000209:etiology / Q000517:prevention & control*; D014945:Wound Healing / Q000187:drug effects*
D003094:Collagen; D011393:Procollagen-Proline Dioxygenase