Abstract
Previous studies have shown disruption of the coronary endothelium and increase in its permeability during ischemia‐reperfusion (I/R) which can be linked with MMPs activity. Our group has shown that during I/R, increased activity of MMP‐2 is associated with cardiac dysfunction, which can be prevented by MMP inhibitors. Therefore, we hypothesize that MMPs inhibition reduces the MMP‐2 dependent disruption of the coronary endothelium during I/R.Isolated rat hearts were perfused in the Langendorff mode at a constant pressure and subjected to 15‐30 min of no‐flow ischemia followed by 30 min of reperfusion. o‐Phenanthroline (Phen), an inhibitor of MMPs, was used to protect the hearts from dysfunction. Endothelial integrity was evaluated by measuring coronary flow, and by measuring the interstitial albumin and serotransferrin in the effluent. MMP‐2 activity was measured in the hearts by zymography.MMP‐2 activity was increased in heart tissue at the end of ischemia and was correlated with duration of ischemia. The coronary flow was decreased and correlated with the disruption of the endothelial barrier (increased release of albumin and serotransferrin in the coronary effluent). Administration of Phen inhibited both reduction of coronary flow and endothelial barrier disruption.
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