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CARDIOVASCULAR ANESTHESIA

Neutrophil-Mediated Secretion and Activation of Matrix Metalloproteinase-9 During Cardiac Surgery with Cardiopulmonary Bypass

Tso-Chou Lin, MD^*, Chi-Yuan Li, MD, MS^*, Chien-Sung Tsai, MD, Chih-Hung Ku, MS, ScD, Ching-Tang Wu, MD^*, Chih-Shung Wong, MD, PhD^*, and Shung-Tai Ho, MD, MS^*

*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

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 cyli{at}ndmctsgh.edu.tw.

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.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999