Protective effect of nafamostat mesilate in early wound healing.
BACKGROUND
Tensile strength in rat ileal anastomosis is diminished after injection with superoxide dismutase. We have studied the immunohistochemistry of extracellular matrix to investigate changes associated with this loss of tensile strength. A serine proteinase inhibitor, Nafamostat mesilate, was used to evaluate its potential for maintaining tensile strength.


METHODS
Four groups of rats underwent ileal anastomosis, Groups 1 and 2 were controls. Groups 3 and 4 were given superoxide dismutase and Nafamostat mesilate, respectively, after anastomosis.


RESULTS
In controls, groups 1 and 2, tensile strength decreased to 58 percent and 57 percent, respectively, of the initial value measured immediately after anastomosis 1 day postoperatively and both dropped to 33 percent 3 days postoperatively. After 5 days, tensile strength recovered to 83 percent of initial value. In comparison with controls, administration of superoxide dismutase significantly attenuated the loss of tensile strength on day 1 (94 percent of initial value, p < 0.01) and on days 3, 5 and 7 (p < 0.05). Similar results were found after administration of Nafamostat mesilate on days 3 and 5 (p < 0.05). In group 1, degradation of the collagen layer in the anastomosis was observed, with disappearance of immunostaining for fibronectin and vitronectin on day 3. In both groups 3 and 4, these changes were significantly attenuated with intense immunostaining for plasminogen activator inhibitor-1; fibronectin and vitronectin were seen particularly among collagen fibers on both sides of the anastomosis.


CONCLUSIONS
These findings suggest that degradation of extracellular matrix causes loss of tensile strength early after anastomosis. Nafamostat mesilate may be clinically useful to prevent breakdown of intestinal anastomoses.
Tsutamoto
Y
Y
First Department of Surgery, Shiga University of Medical Science, Japan.
Tani
T
T
Eguchi
Y
Y
Araki
H
H
Kodama
M
M
D000714:Anastomosis, Surgical; D000818:Animals; D001550:Benzamidines; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007150:Immunohistochemistry; D007422:Intestines / Q000601:surgery; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013718:Tensile Strength / Q000187:drug effects*; D013997:Time Factors; D019096:Vitronectin / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D001550:Benzamidines; D005353:Fibronectins; D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D019096:Vitronectin; D013482:Superoxide Dismutase; C032855:nafamostat