Abstract 2891: Dynamic Changes in Matrix Metalloproteinase Activity within the Human Myocardial Interstitium during Ischemia-Reperfusion
Matrix metalloproteinases (MMPs) contribute to adverse myocardial remodeling with ischemia and reperfusion (I/R). However, MMP levels were measured 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 I/R remained unknown. MMP interstitial activity (MMPact) was quantified within the myocardium of patients (n=13) undergoing elective cardiac surgery during steady-state conditions, as well as during and following an obligatory period of I/R achieved by cardiopulmonary bypass (CPB). Interstitial MMPact was continuously monitored using a validated MMP fluorogenic substrate, a microdialysis system placed within the myocardium, and in-line fluorescent detection system. The MMP fluorogenic substrate would be cleaved by active MMPs from all MMP classes, but not by any other protease system. MMPact, measured as fluoroscence emission, reached a stable steady state level by 10 minutes following deployment of the microdialysis system. A representative continuous, interstitial recording of MMP activity is shown in Fig A⇓ and summary results for all patients is shown in Fig B⇓. During initiation of CPB, MMPact increased by 20% from baseline, and then rapidly fell with cardiac arrest and longer periods of CPB. However, with restoration of myocardial blood flow and separation from CPB, MMPact increased by over 30% from baseline. The present study directly demonstrated that MMP proteolytic activity exists within the human myocardial interstitium and is a dynamic process under conditions such as transient ischemia-reperfusion.