The Clinical Study Of Relation Between MMP-9, TIMP-1 And Left Ventricular Remodeling After Acute Myocardial Infarction

Objective: Heart matrix plays a major role in preserving cardial structure and function.The matrix remodeling in cell level begins within minutes, and progresses in parallel with healing and repair from weeks to months after acute myocardial infarction(AMI); Matrix remodeling leads to myocardial fibrosis, left ventricular dilation and heart failure. Matrix metalloproteinases (MMPs) are the major enzymes to decompose extracelluar matrix, tissue inhibitors of metalloproteinases (TIMPs) are specific inhibitor of MMPs. The degree of left ventricular remodeling (LVRM) is a leading cause to predict prognosis and mortality after AMI. This study measured the sequential changes in serum level of MMP-9 and TIMP-1, and evaluated the relation between MMP-9, TIMP-1 and LVRM of lately period after AMI.Methods: Seventy-one patients with a first acute myocardial infarct were enrolled in our hospital. Thirty-one (group A) patients were performed direct percutaneous coronary intervention( PCI). Forty patients after 12hrs from onset of symptoms were randomly assigned to delayed-PCI (groupB, 20patients) or conservative therapy(groupC, 20patients), and control subjects(groupD, 20patients). All theses patients examined electrocardiogram, creatine phosphokinase levels and observed clinical symptom, physical sign. ACEI, statin , β-receptor inhibitors and aspirin were administered in all patients. Clopidogrel was administered after PCI over 6month. All patients: (1)The blood samples were drawn immediately after admission and 12h, 24h, 3d, 7d, 30d, 90d, 180d. Each blood sample was centrifuged at 3000 rpm and stored at -80℃ until assayed. Enzyme link immuno-assay (ELISA) was used to measure serum MMP-9, TIMP-1. (2) Two-dimensional echocardiography were performed in 3d, 30d, 90d, 180d after myocardial infarction. (3) Major cardiac events were recorded. (4) End-systolic volume index (ESVI), end-diastolic volume index (EDVI) and left ventricular ejection fraction (EF) were evaluated by method of biplane Simpson. Wall motion score index(WMSI) was calculated with the use of the 16 left ventricular wall segments. With a 5mm reference marker to judge wall excursion: 1 for normal(greater than 5mm excursion), 2 for hypokinesis (2 to 5mm excursion ), 3 for akinesis (less than 2mm excursion ), 4 for dyskinesis. WMSI is the sum of wall motion scores for all individual segments evaluated/total number of segments evaluated. Results: There was no statistical difference among 4 groups in the following variables: age, sex, hypertension, smoking and infarction region. The improvement of end-systolic volume index (ESVI), end-diastolic volume index (EDVI) and left ventricular ejection fraction (EF) were significant statistically between A, B and C (P<0.05, respectively) in 30d, 90d, 180d after AMI. The differences of ESVI, EDVI, EF were significant statistically between 30d and 3d in C .The improvement of ESVI, EDVI were significant between 30d and 3d in A and between 90d, 180d and 3d in B (P<0.05 respectively). The improvement of wall motion score index (WMSI) was significant statistically between 30d, 90d, 180d and 3d in group A, B and at the same time inversely in group C. The average serum level of MMP-9, TIMP-1 in group A, B, C was significantly greater than D immediately after admission (P<0.01). The average serum level of MMP-9, TIMP-1 ascended again after PCI in group A, and MMP-9 descended to control subjects level at 7d. The serum level of MMP-9 in group B was significantly greater than control subjects at 7d, descended to control subjects level at 30d. The average serum level of MMP-9, TIMP-1 were significantly greater than control subjects during all observed period. The correlation between average serum level of MMP-9 and EDVI was positive at 30d, and was negative between average serum level of MMP-9 and EF. Conclusion: (1) The serum level of MMP-9 ascended early period and progressed in parallel with healing and repair from weeks to months after AMI. The serum level of MMP-9 descended after reperfusion. During LVRM,...