Role of matrix metalloproteinases in healing of colonic anastomosis.
OBJECTIVE
The aim of this study was to compare the distribution of the matrix metalloproteinases (MMPs) during anastomotic healing in a normal colon with that in an ischemic colon in a rabbit. This family of enzymes degrades all components of connective tissue and has been implicated as a cause of anastomotic dehiscence.


METHODS
A left-sided anastomosis was formed in the distal colon of one group of rabbits, and in the other group, 9 cm of distal colon was made ischemic before resection and anastomosis 12 hours later. Tissues from the anastomosis and sites around the colon were removed at 12 hours, 1 day, and 3 days after anastomosis and, also, at 7 days in the normal group. Distribution of the MMPs and their inhibitor, tissue inhibitor of metalloproteinases (TIMP), was localized by indirect immunofluorescence.


RESULTS
In rabbits having only an anastomosis, the MMPs and TIMP-1 were, at all times, seen solely in the anastomotic segment and were strictly confined to the immediate vicinity of the suture line. While in rabbits with an ischemic colon before anastomosis, the MMPs initially extended several centimeters proximally and distally from the suture line. By the third day, however, there were only minor differences between the two models.


CONCLUSIONS
Distribution of the MMPs and TIMP-1 in normal healing is consistent with a role in the remodeling of colonic anastomosis, but when healing of the colon is compromised, these enzymes are more widespread and may contribute to anastomotic dehiscence.
Savage
F J
FJ
Department of Surgery, University College London Medical School, United Kingdom.
Lacombe
D L
DL
Boulos
P B
PB
Hembry
R M
RM
D000714:Anastomosis, Surgical; D000818:Animals; D001783:Blood Flow Velocity; D003106:Colon / Q000098:blood supply / Q000201:enzymology / Q000601:surgery*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006023:Glycoproteins / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism; D011817:Rabbits; D013529:Surgical Wound Dehiscence / Q000201:enzymology; D019714:Tissue Inhibitor of Metalloproteinases; D014945:Wound Healing
D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D008666:Metalloendopeptidases