| Objectives To observe changes of interstitial collagen network remodeling, matrix metalloproteinase-2, -9 protein expressions and ventricular function after acute myocardial infarction (AMI) in rats, and to evaluate the effects of carvedilol, irbesartan and spironolactone on them in order to investigate the mechanism of collagen network remodeling post acute myocardial infarction and how neuroendocrine activation affects its procedure and corresponding intervention effects.Methods After ligating anterior descending coronary artery, 75 AMI male Sprague-Dawley (SD) rats were randomly assigned to (1) AMI control (n=15); (2)carvedilol (n=15, 10 mg·kg-1·d-1); (3) irbesartan (n=15, 45 mg·kg-1·d-1); (4) spironolactone (n=15, 20mg·kg-1·d-1) groups. Sham-operated group (n=8) were selected randomly as noninfarcted control. After 8 weeks of drug therapy by gastric gavage, hemodynamics and left ventricular function were measured with catheterization; infarcted area, left ventricular dilatation index and sphericity index were measured and calculated using morphological methods; interstitial type I and type III collagen volume fraction (CVF) in the infracted and noninfarcted zone (IZ, NIZ) were analyzed using polarized light by picrosirius red staining; protein expressions of MMP-2 and MMP-9 in left ventricular noninfarcted myocardium were detected by immunohistochemistry.Results Firstly, those dead, infracted area less than 30% or more than 55% and not having integrated datum AMI rats were excluded, and finally there were 8 rats in AMI control group, 9 in carvedilol group, 9 in irbesartan group, 8 in spironolactone group and 8 in sham-operated group. There were no significant difference in infarcted area among the four AMI groups (40.02%44.70%).Secondly, compared with the sham-operated group, left ventricular (LV) end diastolic pressure (LVEDP), left and right relative weight (LVRW, RVRW), thickness of interventricular septum, LV dilatation index, the CVF of type I and type III in the IZ and NIZ ofLV and the protein expressions of MMP-2, -9 in the NIZ of LV were all significantly increased (PO.001) in the control group, in contrast to body weight (BW), blood pressure (BP), left ventricular systolic pressure (LVSP), sphericity index (SI) of LV, the left ventricular pressure maximal rate of rise and fall (± dp/dtmax ) and their adjustment by LVSP (± dp/dtmax/LVSP) were significantly decreased (P<0.001). Thirdly, compared with the AMI control group, there were no significant difference in BW, BP, LVSP, left and right ventricular actual weight (LVAW, RVAW) and the CVF of type I and type III in the IZ in carvedilol and irbesartan therapy groups. However, LVEDP, LVRW, RVRW, thickness of interventricular septum, dilatation index of LV, type I CVF and protein expressions of MMP-2, -9 in the NIZ of LV were all decreased (PO.050.001), while SI, ± dp/dtmax and ± dp/dtmax/LVSP were significantly increased (PO.010.001) in these two drug therapy groups. Fourthly, compared with the AMI control group, LVEDP, type I CVF and protein expressions of MMP-2, -9 in the NIZ of LV were all significantlydecreased (P<0.050.001) in spironolactone therapy group, while ± dp/dtmax and± dp/dtmax/LVSP were significantly increased (PO.050.001) and no significant effect on other parameters. Fifthly, carvedilol can significantly decrease HR of the AMI rats compared with the AMI control group (PO.05). Sixthly, +dp/dtmax/LVSP were significantly increased in the irbesartan group compared with spironolactone group (P<0.05).Conclusions Firstly, manifestations of late ventricular remodeling after AMI includes LV dilatation, myocardium thickening in NIZ, and spherical shape change, interstitial fibrosis, increased protein expressions of MMP-2, -9 and ventricular function deterioration. Secondly, carvedilol and irbesartan can... |
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