Related Experiment Video
Updated: May 2, 2026
A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Ischaemia-reperfusion injury activates matrix metalloproteinases in the human heart
Manoj M Lalu1, Evasio Pasini, Costas J Schulze
1Department of Pharmacology, University of Alberta, Edmonton, Canada.
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.
Insights
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) increase in human hearts after bypass surgery. This MMP activation correlates with impaired cardiac function, suggesting a role in myocardial stunning.
Area of Science:
- Cardiovascular Biology
- Enzymology
- Surgical Research
Background:
- Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are key regulators of cardiac matrix remodeling.
- Previous studies in rats indicated their involvement in myocardial dysfunction following ischemia-reperfusion injury.
Purpose of the Study:
- To investigate the dynamic changes in MMPs and TIMPs in human myocardium and plasma during acute myocardial ischemia-reperfusion injury.
- To correlate MMP/TIMP activity with cardiac mechanical function post-reperfusion in patients undergoing coronary artery bypass grafting.
Main Methods:
- Analysis of left atrial biopsies and plasma samples from 15 patients undergoing coronary artery bypass grafting.
- Measurement of MMP-2, MMP-9, and TIMP-1 activities at various time points before and after reperfusion.
- Monitoring of left ventricular stroke work index to assess cardiac mechanical function.
Main Results:
- Reperfusion significantly increased myocardial MMP-2 and MMP-9 activities and decreased TIMP-1 levels.
- Increased MMP activity correlated with longer cross-clamp times and poorer cardiac function post-reperfusion.
- Plasma MMP-9 and MMP-2 activities elevated rapidly within 1 minute of reperfusion.
Conclusions:
- Coronary artery bypass grafting with cardioplegia activates MMPs in the human myocardium and plasma.
- This study provides the first direct correlation between myocardial MMP activity and cardiac function in humans.
- Early MMP activation creates a proteolytic environment potentially contributing to myocardial stunning post-reperfusion.
Related Concept Videos
01:42The Extracellular Matrix
01:29The Extracellular Matrix
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
01:23Role of Matrix Metalloproteases in Degradation of ECM
01:28Phases of Wound Repair
Formation of Blood Clot
In case of deep injuries, trauma to blood vessels results in blood loss. In the meantime, phospholipids released from the ruptured endothelial cellular membrane are converted into arachidonic...
01:20Blood Studies for Cardiovascular System I: Cardiac Biomarkers
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...
01:21Myocarditis I: Introduction