Matrix metalloproteinases and collagen ultrastructure in moderate myocardial ischemia and reperfusion in vivo

Severe ischemic injury or infarction of myocardium may cause activation of matrix metalloproteinases (MMPs) and damage the interstitial matrix. Howeve r, it is unknown whether MMP activation and matrix damage occur after moder ate ischemia and reperfusion that result in myocardial stunning without inf arction, and if so whether such changes contribute to postischemic myocardi al expansion and contractile dysfunction. To address these questions, open- chest anesthetized pigs underwent 90 min of regional ischemia (subendocardi al blood flow 0.4 +/- 0.1 ml . g(-1) . min(-1)) and 90 min of reperfusion. After ischemia plus reperfusion, histological and ultrastructural examinati on revealed no myocardial infarction or inflammatory cell infiltration. Myo cardial MMP-9 content increased threefold with a fourfold increase in the a ctive form (P < 0.001). Myocardial collagenase content doubled (P < 0.01) b ut remained in latent form. MMP-2 and tissue inhibitors of metalloproteinas es were unaffected. Despite increases in MMPs, collagen ultrastructure (ass essed by cell maceration scanning electron microscopy) was unaltered. Intra coronary administration of the MMP inhibitor GM-2487 did not prevent or att enuate myocardial expansion (assessed by regional diastolic dimensions at n ear-zero left ventricular pressure) or contractile dysfunction. We conclude that although moderate ischemia and reperfusion alter myocardial MMP conte nt and activity, these effects do not result in damage to interstitial coll agen, nor do they contribute to myocardial expansion or contractile dysfunc tion.