Skip Navigation


European Heart Journal Advance Access originally published online on November 30, 2004
European Heart Journal 2005 26(1):27-35; doi:10.1093/eurheartj/ehi007
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
26/1/27    most recent
ehi007v1
Right arrow Alert me when this article is cited
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 ISI Web of Science
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 arrow Search for citing articles in:
ISI Web of Science (19)
Right arrowRequest Permissions
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. Lalu1,2,{dagger}, Evasio Pasini3,{dagger}, Costas J. Schulze2,4, Mario Ferrari-Vivaldi5, Gianna Ferrari-Vivaldi5, Tiziana Bachetti3 and Richard Schulz1,2,4,*

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

Received March 26, 2004; revised September 23, 2004; accepted October 7, 2004 * Corresponding author: Cardiovascular Research Group, 4-62 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2. Tel: +1 780 492 6581; fax: +1 780 492 9753. E-mail address: richard.schulz{at}ualberta.ca

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 24 h following reperfusion. Left atrial biopsy samples were obtained at the start of bypass before cardioplegia and within 10 min after removal of the aortic cross-clamp. Plasma samples were collected from the radial artery and coronary sinus 1, 5, and 10 min following removal of the cross-clamp. In cardiac biopsies there was a marked increase in 72 kDa MMP-2 and 92 kDa 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 3 h following reperfusion. TIMP-1 correlated inversely with cross-clamp time and positively with cardiac mechanical function. Plasma samples revealed a significant increase in both 92 kDa MMP-9 and 64 kDa MMP-2 activities 1 min 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.

Key Words: 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
 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.