Severe ischemic injury or
infarction of myocardium may cause activation of
matrix metalloproteinases (
MMPs) and damage the interstitial matrix. However, it is unknown whether
MMP activation and matrix damage occur after moderate
ischemia and reperfusion that result in
myocardial stunning without
infarction, and if so whether such changes contribute to postischemic myocardial expansion and contractile dysfunction. To address these questions, open-chest anesthetized pigs underwent 90 min of regional
ischemia (subendocardial blood flow 0.4 +/- 0.1 ml. g(-1). min(-1)) and 90 min of reperfusion. After
ischemia plus reperfusion, histological and ultrastructural examination revealed no
myocardial infarction or inflammatory cell infiltration. Myocardial MMP-9 content increased threefold with a fourfold increase in the active form (P < 0.001). Myocardial
collagenase content doubled (P < 0.01) but remained in latent form. MMP-2 and tissue inhibitors of
metalloproteinases were unaffected. Despite increases in
MMPs,
collagen ultrastructure (assessed by cell maceration scanning electron microscopy) was unaltered. Intracoronary administration of the
MMP inhibitor GM-2487 did not prevent or attenuate myocardial expansion (assessed by regional diastolic dimensions at near-zero left ventricular pressure) or contractile dysfunction. We conclude that although moderate
ischemia and reperfusion alter myocardial
MMP content and activity, these effects do not result in damage to interstitial
collagen, nor do they contribute to myocardial expansion or contractile dysfunction.