HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): David Johnson Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mayers, I. Articles by Radomski, M. W. Search for Related Content PubMed PubMed Citation Articles by Mayers, I. Articles by Radomski, M. W. Related Collections Cardiac - pharmacology Cardiac - physiology

J Thorac Cardiovasc Surg 2001;122:746-752
© 2001 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Cardiac surgery increases the activity of matrix metalloproteinases and nitric oxide synthase in human hearts

From the Departments of Medicine, Pathology, and Pharmacology, University of Alberta, Edmonton, Alberta, Canada, and the Departments of Medicine, Anaesthesia, and Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Supported by a grant from the Saskatchewan Heart and Stroke Foundation.

Received for publication Oct 23, 2000. Revisions requested Dec 21, 2000; revisions received March 23, 2001. Accepted for publication March 26, 2001. Address for reprints: Irvin Mayers, MD, Department of Medicine, Room 2E4.37, Walter C. Mackenzie Health Sciences Center, Edmonton, Alberta, Canada, T6G 2B7 (E-mail: imayers{at}ualberta.ca).

Objectives: Heart function is variably impaired after cardiopulmonary bypass. We hypothesized that, similar to other myocardial injury states, cardiopulmonary bypass leads to enhanced activity of nitric oxide synthase and matrix metalloproteinases.
Methods: We obtained right atrial biopsy specimens and plasma samples at the onset and termination of cardiopulmonary bypass in 10 patients. Biopsy specimens were analyzed for nitric oxide synthase activity by using a citrulline assay, whereas plasma and tissue were analyzed for matrix metalloproteinase-9 and matrix metalloproteinase-2 activity by using zymography. Tissue inhibitor of metalloproteinase-4 was analyzed by means of Western blotting. The cellular expression of inducible nitric oxide, endothelial nitric oxide synthase, matrix metalloproteinase-2, and matrix metalloproteinase-9 was determined in right atrial biopsy samples from 3 additional patients by using the appropriate conjugated antibodies.
Results: Nitric oxide synthase activity increased from the beginning to the end of bypass (4.46 ± 1.07 vs 16.77 ± 4.86 pmol citrulline/mg of protein per minute, respectively; P = .018). Pro-matrix metalloproteinase-9 activity increased in hearts (199 ± 41 vs 660 ± 177 density units/mg protein; P = .008) and plasma (14.1 ± 4.6 vs 52.2 ± 5.9 density units/mg protein; P = .008). Pro-matrix metalloproteinase-2 activity increased in the heart (201 ± 23 vs 310 ± 35 density units/mg protein, P < .05) but not in plasma. Tissue inhibitor of metalloproteinase-4 expression in the heart decreased (1574 ± 280 vs 864 ± 153 density units, P = .014).
Conclusions: Cardiopulmonary bypass activates enzymes mediating acute inflammation and organ injury (ie, nitric oxide synthase, matrix metalloproteinase-9, and matrix metalloproteinase-2). Decreased tissue inhibitor of metalloproteinase-4 expression allows relatively unopposed increases in matrix metalloproteinase tissue activity. We postulate that these changes play a role in the pathogenesis of heart dysfunction after bypass surgery.

This article has been cited by other articles:

				A. Sokal, M. Zembala, A. Radomski, A. Kocher, J. Pacholewicz, J. Los, E. Jedrzejczyk, M. Zembala, and M. Radomski A differential release of matrix metalloproteinases 9 and 2 during coronary artery bypass grafting and off-pump coronary artery bypass surgery. J. Thorac. Cardiovasc. Surg., May 1, 2009; 137(5): 1218 - 1224. [Abstract] [Full Text] [PDF]

				F. G. Spinale, C. N. Koval, A. M. Deschamps, R. E. Stroud, and J. S. Ikonomidis Dynamic Changes in Matrix Metalloprotienase Activity Within the Human Myocardial Interstitium During Myocardial Arrest and Reperfusion Circulation, September 30, 2008; 118(14_suppl_1): S16 - S23. [Abstract] [Full Text] [PDF]

				C. S.H. Ng, A. A. Arifi, S. Wan, A. M.H. Ho, I. Y.P. Wan, E. M.C. Wong, and A. P.C. Yim Ventilation During Cardiopulmonary Bypass: Impact on Cytokine Response and Cardiopulmonary Function Ann. Thorac. Surg., January 1, 2008; 85(1): 154 - 162. [Abstract] [Full Text] [PDF]

				F. G. Spinale Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function Physiol Rev, October 1, 2007; 87(4): 1285 - 1342. [Abstract] [Full Text] [PDF]

				M. Marcet-Palacios, M. Ulanova, F. Duta, L. Puttagunta, S. Munoz, D. Gibbings, M. Radomski, L. Cameron, I. Mayers, and A. D. Befus The Transcription Factor Wilms Tumor 1 Regulates Matrix Metalloproteinase-9 through a Nitric Oxide-Mediated Pathway J. Immunol., July 1, 2007; 179(1): 256 - 265. [Abstract] [Full Text] [PDF]

				C. D. Mazer, F. Briet, K. R. Blight, D. J. Stewart, M. Robb, Z. Wang, A. M. Harrington, W. Mak, X. Li, and G. M.T. Hare Increased cerebral and renal endothelial nitric oxide synthase gene expression after cardiopulmonary bypass in the rat J. Thorac. Cardiovasc. Surg., January 1, 2007; 133(1): 13 - 20. [Abstract] [Full Text] [PDF]

				L. B. Stacy, Q. Yu, K. Horak, and D. F Larson Effect of angiotensin II on primary cardiac fibroblast matrix metalloproteinase activities Perfusion, January 1, 2007; 22(1): 51 - 55. [Abstract] [PDF]

				R. Ryan, J. Thornton, E. Duggan, E. McGovern, M. J. O'Dwyer, A. W. Ryan, D. Kelleher, R. McManus, and T. Ryan Gene polymorphism and requirement for vasopressor infusion after cardiac surgery. Ann. Thorac. Surg., September 1, 2006; 82(3): 895 - 901. [Abstract] [Full Text] [PDF]

				A. Franco-Cereceda, P. Holm, F. Bredin, and C. Adding Attenuation of postoperative noradrenaline need by nitric oxide inhibition using L-NMMA Eur J Heart Fail, December 1, 2005; 7(7): 1180 - 1182. [Abstract] [Full Text] [PDF]

				T.-C. Lin, C.-Y. Li, C.-S. Tsai, C.-H. Ku, C.-T. Wu, C.-S. Wong, and S.-T. Ho Neutrophil-Mediated Secretion and Activation of Matrix Metalloproteinase-9 During Cardiac Surgery with Cardiopulmonary Bypass Anesth. Analg., June 1, 2005; 100(6): 1554 - 1560. [Abstract] [Full Text] [PDF]

				M. M. Lalu, E. Pasini, C. J. Schulze, M. Ferrari-Vivaldi, G. Ferrari-Vivaldi, T. Bachetti, and R. Schulz Ischaemia-reperfusion injury activates matrix metalloproteinases in the human heart Eur. Heart J., January 1, 2005; 26(1): 27 - 35. [Abstract] [Full Text] [PDF]

				C. J. Schulze, W. Wang, W. L. Suarez-Pinzon, J. Sawicka, G. Sawicki, and R. Schulz Imbalance Between Tissue Inhibitor of Metalloproteinase-4 and Matrix Metalloproteinases During Acute Myoctardial Ischemia-Reperfusion Injury Circulation, May 20, 2003; 107(19): 2487 - 2492. [Abstract] [Full Text] [PDF]

				I. Mayers, T. Hurst, A. Radomski, D. Johnson, S. Fricker, G. Bridger, B. Cameron, M. Darkes, and M. W. Radomski Increased matrix metalloproteinase activity after canine cardiopulmonary bypass is suppressed by a nitric oxide scavenger J. Thorac. Cardiovasc. Surg., March 1, 2003; 125(3): 661 - 668. [Abstract] [Full Text] [PDF]

				U. Mehlhorn and W. Bloch Role of cardiopulmonary bypass and cardioplegic arrest in the regulation of cardiac nitric oxide synthase activity J. Thorac. Cardiovasc. Surg., August 1, 2002; 124(2): 418 - 419. [Full Text] [PDF]

				P. Jurasz, A. W.Y. Chung, A. Radomski, and M. W. Radomski Nonremodeling Properties of Matrix Metalloproteinases: The Platelet Connection Circ. Res., May 31, 2002; 90(10): 1041 - 1043. [Full Text] [PDF]