Dynamic changes in matrix metalloprotienase activity within the human myocardial interstitium during myocardial
Francis G Spinale1, Christine N Koval, Anne M Deschamps
1Cardiothoracic Surgery, Strom Thurmond Research Center, 114 Doughty St, Suite 625, Charleston, SC 29425, USA.
Background:
Past studies have clearly established that matrix metalloproteinases (MMPs) contribute to adverse myocardial remodeling with ischemia and reperfusion. However, these studies measured MMP levels in extracted samples, and therefore whether and to what degree actual changes in interstitial MMP activity occur within the human myocardium in the context of ischemia/reperfusion remained unknown.
Methods And Results:
The present study directly quantified MMP interstitial activity within the myocardium of patients (n=14) undergoing elective cardiac surgery during steady-state conditions, as well as during and following an obligatory period of myocardial arrest and reperfusion achieved by cardiopulmonary bypass. Interstitial MMP activity was continuously monitored using a validated MMP fluorogenic substrate, a microdialysis system placed within the myocardium, and in-line fluorescent detection system. MMP activity, as measured by fluorescent emission, reached a stable steady state level by 10 minutes after deployment of the microdialysis system. During initiation of cardiopulmonary bypass, MMP activity increased by 20% from baseline values (P<0.05), and then rapidly fell with cardiac arrest and longer periods of cardiopulmonary bypass. However, with restoration of myocardial blood flow and separation from cardiopulmonary bypass, MMP interstitial activity increased by over 30% from baseline (P<0.05).
Conclusions:
The present study directly demonstrated that MMP proteolytic activity exists within the human myocardial interstitium and is a dynamic process under conditions such as myocardial arrest and reperfusion.
Insights
Matrix metalloproteinases (MMPs) activity in the human heart interstitium is dynamic. This study shows MMP interstitial activity increases significantly after reperfusion following cardiac arrest.
Area of Science:
- Cardiovascular Biology
- Enzymology
- Myocardial Pathophysiology
Background:
- Matrix metalloproteinases (MMPs) are implicated in adverse myocardial remodeling post-ischemia/reperfusion.
- Previous studies relied on extracted samples, leaving in-situ interstitial MMP activity in the human myocardium unknown.
Purpose of the Study:
- To directly quantify interstitial matrix metalloproteinase (MMP) activity within the human myocardium during ischemia and reperfusion.
- To investigate the dynamic changes in myocardial MMP activity during cardiac surgery involving cardiopulmonary bypass.
Main Methods:
- Utilized a microdialysis system with a validated MMP fluorogenic substrate placed within the myocardium of 14 patients.
- Continuously monitored interstitial MMP activity using in-line fluorescent detection during steady-state, cardiac arrest, and reperfusion.
- Measured changes in MMP activity relative to baseline values during cardiopulmonary bypass and separation.
Main Results:
- Interstitial MMP activity reached a stable baseline within 10 minutes of microdialysis system deployment.
- MMP activity increased by 20% during cardiopulmonary bypass initiation, then decreased with cardiac arrest.
- Following reperfusion and separation from bypass, interstitial MMP activity rose by over 30% from baseline.
Conclusions:
- Directly demonstrated the presence and dynamic nature of matrix metalloproteinase (MMP) proteolytic activity within the human myocardial interstitium.
- Showcased that myocardial arrest and reperfusion significantly alter interstitial MMP activity in vivo.
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