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 MMP-9 expression.


METHODS
In the in vitro experiment, the authors tested the hypothesis of a direct inhibition of MMP-9 by the fluids used perioperatively, i.e., lactated Ringer's solution, 3.4% poligeline, and hydroxyethyl starch 130/0.4. In the in vivo experiment, 36 patients undergoing surgery for colon cancer were randomly assigned to three groups to receive lactated Ringer's solution, poligeline, or hydroxyethyl starch. MMP-9 and tissue inhibitor of metalloproteinases were measured from venous blood samples; the MMP-9/tissue inhibitor of metalloproteinases ratio was calculated as an index of equilibrium between the action of MMP-9 and its inhibition.


RESULTS
In the in vitro experiment, the presence of hydroxyethyl starch 130/0.4 in the MMP-9 assay system showed a strong inhibition of the enzymatic activity compared with lactated Ringer's solution. In the in vivo experiment, MMP-9 and tissue inhibitor of metalloproteinases plasma levels did not differ among the three groups at baseline, whereas those levels increased significantly at the end of surgery. At that time, the MMP-9 plasma levels and the MMP-9/tissue inhibitor of metalloproteinases ratio were significantly higher in the lactated Ringer's solution and poligeline groups than in the hydroxyethyl starch group. These results were confirmed 72 h after surgery.


CONCLUSIONS
This study demonstrates that hydroxyethyl starch 130/04 decreases the circulating levels of MMP-9 in patients undergoing abdominal surgery.
Volta
Carlo A
CA
Section of Anesthesia and Intensive Care, Multiple Sclerosis Center, Department of Neurology, Anna Hospital, University of Ferrara, Italy. vic@dns.unife.it
Alvisi
Valentina
V
Campi
Matilde
M
Marangoni
Elisabetta
E
Alvisi
Raffaele
R
Castellazzi
Massimiliano
M
Fainardi
Enrico
E
Manfrinato
Maria C
MC
Dallocchio
Franco
F
Bellini
Tiziana
T
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use*; D007552:Isotonic Solutions / Q000627:therapeutic use; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010952:Plasma Substitutes / Q000627:therapeutic use*; D011097:Polygeline / Q000627:therapeutic use; D000077325:Ringer's Lactate; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D061965:Matrix Metalloproteinase Inhibitors; D010952:Plasma Substitutes; D000077325:Ringer's Lactate; D019715:Tissue Inhibitor of Metalloproteinase-1; D011097:Polygeline; D020780:Matrix Metalloproteinase 9; D010100:Oxygen