Skip Navigation



European Heart Journal Advance Access published online on November 30, 2004
European Heart Journal, doi:10.1093/eurheartj/ehi007
Copyright © 2004 by the European Society of Cardiology.
This Article
Right arrow Full Text (Rapid PDF)
Right arrow All Versions of this Article:
26/1/27    most recent
ehi007v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Lalu, M. M.
Right arrow Articles by Schulz, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lalu, M. M.
Right arrow Articles by Schulz, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Clinical research

Ischaemia-reperfusion injury activates matrix metalloproteinases in the human heart

Manoj M. Lalu 1, Evasio Pasini 2, Costas J. Schulze 3, Mario Ferrari-Vivaldi 4, Gianna Ferrari-Vivaldi 4, Tiziana Bachetti 2, and Richard Schulz 5*

1 Department of Pharmacology, University of Alberta, Edmonton, Canada; Cardiovascular Research Group, University of Alberta, Edmonton, Canada
2 Fondazione S. Maugeri, IRCCS, Clinica del Lavoro e della Riabilitazione, Centro Medico di Gussago, Divisione di Cardiologia, Gussago (BS), Italy
3 Cardiovascular Research Group, University of Alberta, Edmonton, Canada; Department of Paediatrics, University of Alberta, Edmonton, Canada
4 Cardiovascular Surgery Department, San Rocco Hospital, Ome (BS), Italy
5 Department of Pharmacology, University of Alberta, Edmonton, Canada; Cardiovascular Research Group, 4-62 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Department of Paediatrics, University of Alberta, Edmonton, Canada

* To whom correspondence should be addressed.
Richard Schulz, E-mail: richard.schulz{at}ualberta.ca


  Abstract

Aims Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate matrix remodelling in the heart and play a pivotal role in myocardial dysfunction immediately following ischaemia-reperfusion injury ex vivo in rats. We investigated the changes in MMPs and TIMPs in acute myocardial ischaemia-reperfusion injury in humans.

Methods and results Fifteen patients with stable angina undergoing coronary artery bypass graft surgery with cardiopulmonary bypass were enrolled. Left ventricular stroke work index was monitored prior to bypass and for 24h following reperfusion. Left atrial biopsy samples were obtained at the start of bypass before cardioplegia and within 10min after removal of the aortic cross-clamp. Plasma samples were collected from the radial artery and coronary sinus 1, 5, and 10min following removal of the cross-clamp. In cardiac biopsies there was a marked increase in 72kDa MMP-2 and 92kDa MMP-9 activities, and a decrease in TIMP-1 upon reperfusion. Increased MMP activity correlated positively with cross-clamp duration and inversely with cardiac mechanical function 3h following reperfusion. TIMP-1 correlated inversely with cross-clamp time and positively with cardiac mechanical function. Plasma samples revealed a significant increase in both 92kDa MMP-9 and 64kDa MMP-2 activities 1min following removal of cross-clamp.

Conclusion Reperfusion following cardioplegia activates MMPs in the myocardium and plasma of patients undergoing coronary artery bypass grafting. This is the first correlation of MMP myocardial activity with cardiac function in humans. The early increase in MMP activity produces a proteolytic environment that may contribute to myocardial stunning injury in humans.

Keywords: Matrix metalloproteinase; Tissue inhibitor of metalloproteinase; Ischaemia-reperfusion; Heart surgery.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
A. D. Kandasamy, A. K. Chow, M. A.M. Ali, and R. Schulz
Matrix metalloproteinase-2 and myocardial oxidative stress injury: beyond the matrix
Cardiovasc Res, August 20, 2009; (2009) cvp268v2.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
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]

Home page
 CirculationHome page
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]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
A. M. Deschamps, J. Zavadzkas, R. L. Murphy, C. N. Koval, J. E. McLean, L. Jeffords, S. M. Saunders, N. J. Sheats, R. E. Stroud, and F. G. Spinale
Interruption of endothelin signaling modifies membrane type 1 matrix metalloproteinase activity during ischemia and reperfusion
Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H875 - H883.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
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]

Home page
 PerfusionHome page
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]

Home page
 Cardiovasc ResHome page
S. Janssens and H. R. Lijnen
What has been learned about the cardiovascular effects of matrix metalloproteinases from mouse models?
Cardiovasc Res, February 15, 2006; 69(3): 585 - 594.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
G.-Y. Wang, M. R. Bergman, A. P. Nguyen, S. Turcato, P. M. Swigart, M. C. Rodrigo, P. C. Simpson, J. S. Karliner, D. H. Lovett, and A. J. Baker
Cardiac transgenic matrix metalloproteinase-2 expression directly induces impaired contractility
Cardiovasc Res, February 15, 2006; 69(3): 688 - 696.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
Z. Giricz, M. M. Lalu, C. Csonka, P. Bencsik, R. Schulz, and P. Ferdinandy
Hyperlipidemia Attenuates the Infarct Size-Limiting Effect of Ischemic Preconditioning: Role of Matrix Metalloproteinase-2 Inhibition
J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 154 - 161.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.