Influence of different strategies of volume replacement on the activity of matrix metalloproteinases: an in vitro and in vivo study

Background: Excessive production of matrix metalloproteinase 9 (MMP-9) is linked to tissue damage and anastomotic leakage after large bowel surgery. Hence the aim of this study was to verify whether different strategies of fluids administration can reduce the MMP-9 expression. Methods: 1) In vitro experiment: we tested the hypothesis of a direct inhibition of MMP-9 by the fluids used perioperatively, i.e. lactated Ringer’s solution, poligeline 3.4%, and the hydroxyethyl starch 130/0.4; 2) In vivo experiment: thirty-six patients undergoing surgery for colon cancer were randomized to three different groups to receive either lactated Ringer’s solution, poligeline or hydroxyethyl starch. MMP-9 and tissue inhibitor of metalloproteinases were measured from venous blood samples; MMP-9/tissue inhibitor of metalloproteinases ratio was calculated as an index of equilibrium between the action of MMP-9 and its inhibition. Results: 1) In vitro experiment: the presence of hydroxyethyl starch 130/0.4 in the MMP9 assay system showed a strong inhibition of the enzymatic activity compared to lactated Ringer’s solution; 2) In vivo experiment: MMP-9 and tissue inhibitor of metalloproteinases plasma levels did not differ among the three groups at the baseline while those levels increased significantly at the end of surgery. At this time, the MMP-9 plasma levels as well as MMP-9/tissue inhibitor of metalloproteinases ratio were significantly higher in lactated Ringer’s solution and poligeline groups than in hydroxyethyl starch group. These results were confirmed 72 h after surgery. Conclusions: Our study demonstrates that the hydroxyethyl starch 130/04 decreases the circulating levels of MMP-9 in patients undergoing abdominal surgery.