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Ann Thorac Surg 2001;71:1518-1523
© 2001 The Society of Thoracic Surgeons

Original article: cardiovascular

Cardiopulmonary bypass induces the synthesis and release of matrix metalloproteinases

Cassandra Joffs, MDa, Himali R. Gunasinghe, BSa, Marlina M. Multani, BSa, B. Hugh Dorman, MD, PhDa, John M. Kratz, MDa, A. Jackson Crumbley, III, MDa, Fred A. Crawford, Jr, MDa, Francis G. Spinale, MD, PhDa

a Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA

Accepted for publication January 5, 2001.

Address reprint requests to Dr Spinale, Division of Cardiothoracic Surgery, Medical University of South Carolina, 114 Doughty St, Suite 625, Charleston, SC 29425

Background. A number of cellular and molecular events can be induced after cardiac procedures requiring cardiopulmonary bypass (CPB). The matrix metalloproteinases (MMPs) are a recently discovered family of enzymes that degrade the extracellular matrix, but expression during and after CPB is unknown.

Methods. Systemic plasma MMP levels were measured in patients (n = 28, 63 ± 1 years) undergoing elective coronary revascularization requiring CPB at baseline, termination of CPB, and 30 minutes, 6 and 24 hours after CPB. Representative classes of MMP species known to degrade matrix and basement membrane components were selected for study. Specifically, the interstitial collagenases MMP-8 and MMP-13, and the gelatinases MMP-2 and MMP-9 were determined by internally validated enzyme-linked immunosorbent assay.

Results. The MMP-8 levels increased by fourfold at separation from CPB, and returned to within normal values within 30 minutes after CPB. The proenzyme forms of MMP-13 and MMP-9 increased by more than twofold at cross-clamp release and returned within normal limits within 6 hours after CPB. The proform of MMP-2 increased from baseline values at 6 and 24 hours postoperatively; likely indicative of de novo synthesis.

Conclusions. A specific portfolio of MMPs are released and synthesized during and after CPB. Because MMPs can degrade extracellular proteins essential for maintaining normal cellular architecture and function, enhanced MMP release and activation may contribute to alterations in tissue homeostasis in the early postoperative period.




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