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(Circulation. 2008;118:S16-S23.)
© 2008 American Heart Association, Inc.

Myocardial Protection, Perioperative Management, and Vascular Biology

Dynamic Changes in Matrix Metalloprotienase Activity Within the Human Myocardial Interstitium During Myocardial Arrest and Reperfusion

Francis G. Spinale, MD, PhD; Christine N. Koval, BS; Anne M. Deschamps, PhD; Robert E. Stroud, MS; John S. Ikonomidis, MD, PhD

From the Division of Cardiothoracic Surgery (C.N.K., A.M.D., R.E.S.), Medical University of South Carolina, Charleston; and Ralph H. Johnson Veteran’s Affairs Medical Center (F.G.S., J.S.I.), Charleston, SC.

Correspondence to Francis G. Spinale, MD, PhD, Cardiothoracic Surgery, Strom Thurmond Research Center, 114 Doughty St, Suite 625, Charleston, SC 29425. E-mail wilburnm{at}musc.edu

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.

Key Words: microdialysis • cardiac surgery • fluorogenic substrates • extracellular matrix

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