Cardiopulmonary bypass (CPB) induces neutrophil activation, degranulation, and a systemic inflammatory response. Matrix metalloproteinase (MMP)-9 exists in neutrophils and is released on neutrophil activation. Increased levels of MMP-9 have been observed in patients undergoing CPB. We designed the present study to determine whether MMP-9 is derived from neutrophils during CPB. Twenty-one patients undergoing elective coronary artery bypass grafting with or without CPB were included in this study. Blood was collected and analyzed for MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1. Neutrophils were also isolated and examined for MMP-9 production and mRNA expression. Plasma levels and activity of MMP-9 increased significantly 2–6 h after beginning CPB, whereas the MMP-9 levels in patients with off-pump cardiac surgery did not increase. The neutrophil content of MMP-9 and mRNA increased significantly 2 h after beginning CPB. The plasma levels of TIMP-1 increased gradually for 6 h, whereas the MMP-9/TIMP-1 ratios were increased 2–4 h after beginning CPB. The present study demonstrated that CPB causes an increase in the concentration and activity of plasma MMP-9. The corresponding increase in neutrophil MMP-9 expression and production suggests that MMP-9 is derived primarily from neutrophils and may contribute to the inflammatory response associated with CPB.
IMPLICATIONS: The present study demonstrated increased matrix metalloproteinase (MMP)-9 levels in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) but not in patients receiving off-pump cardiac surgery. The corresponding increase in neutrophil MMP-9 expression and production suggests that MMP-9 is derived primarily from neutrophils and may contribute to the inflammatory response associated with CPB.
*Department of Anesthesiology and †Surgery, Tri-Service General Hospital; and ‡School of Public Heath, National Defense Medical Center, National Defense University, Taipei, Taiwan, Republic of China
Supported, in part, by grants from Tri-Service General Hospital (TSGH-C92–42) and the National Science Council (NSC 92–2314-B-016–056), Taiwan, ROC.
Accepted for publication December 9, 2004.
Address correspondence and reprint requests to Chi-Yuan Li, MD, MS, Department of Anesthesiology, Tri-Service General Hospital, #325, Section 2, Cheng-Gong Rd., 114 Nei-Hu Dist, Taipei, Taiwan, Republic of China. Address e-mail to firstname.lastname@example.org.