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. 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.
Cardiology Section, Department of Veterans Affairs Medical Center and Division of Cardiology, University of Colorado Health Sciences Center, Denver, Colorado 80220, USA.
L
L
Lu
Z
Z
Gunja-Smith
J F
JF
Woessner
P C
PC
Ursell
T
T
Nissen
R E
RE
Galardy
Y
Y
Xu
P
P
Zhu
G G
GG
Schwartz
D000818:Animals; D001794:Blood Pressure; D003094:Collagen / Q000648:ultrastructure*; D017364:Collagenases / Q000378:metabolism; D003326:Coronary Circulation; D005260:Female; D006321:Heart / Q000503:physiopathology; D006339:Heart Rate; D006439:Hemodynamics; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure*; D013552:Swine; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D016277:Ventricular Function, Left
D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D017364:Collagenases; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9