| Backgroud and Objective Myocardial infarction frequentlyproduces left ventricular dilatation associated with myocyte hypertrophy andinterstitial fibrosis of the myocardium. These changes in LV geometry, referedto as remodeling, contribute to the development of depressed cardiacperformance. Myocardial apoptosis,a distinct type of cell death from necrosis,has recently been shown to occure in myocardial infarction and might play animportant role in the cardiac remodeling after MI. Angiotensin-convertingenzyme(ACE) inhibitor and angiotensin II type 1 receptor blocker(ARB) eachalone can attenuate LV remodeling, improve the quality of life and decreasethe mortality and morbility of patients with MI. Because of their differentpharmacological mechanism, combination therapy with ACE inhibitors andARB may offer benefits beyond those of either agent alone. Although theircombination has been shown to reduce blood pressure,plasma aldosterone andend systolic LV volume in an additive manner, it is still controversial whethercombination therapy is more effective on cardiac remodeling than each agentalone. Furthermore, ACEI and ARB had been showed to reduce myocardialapoptosis, but the effect on myocardial apoptosis by the combination therapyhasn't been reported up to now. Therefore, the purpose of this study was toobserve the changes of myocardial apoptosis and cardiac remodelingparameters after myocardial infarction and to evaluate the effects ofcombination therapy with the two drugs as compared to those of either agentalone on cardiac remodeling and myocardial apoptosis after MI. Methods The AMI rat model was established by ligation of the leftanterior descending coronary artery, the Sham-operated rats underwent thesame procedure except for the ligation .(1)In the first part of the study, 30infarcted rats were randomly divided into 24h group,3d group,7d group,14d group and 28d group(n=6 in each group) and meanwhile, used Shamgroup as controls at different time points. The hemodynamic parameters wereanalyzed by ALC –MPA Biological Signal Analysis System; Some cardiacmorphological parameters including LVWI,LVLA were measured when thehearts were harvested; The other parameters like LVIP,cardiomyocytediameter of non-infarcted myocardium was detected under HE staining; Tomeasure myocardial apoptosis, TUNEL staining (terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay) was performed accordingto the manufacturer's instructions; The expression of Bax and Bcl-2 proteinwere evaluated by immunohischemistry and image analysis; (2) In the secondpart of the study, 18 infarcted rats that survived after coronary ligation wererandomly divided into three groups: Enalapril treated group(5mg.kg-1.d-1),Telmisartan treated group (20mg.kg-1.d-1) and Combination treated group(2.5mg Enalapril.kg-1.d-1 + 10mg Telmisartan.kg-1.d-1). All drugs were orallygiven to AMI rats by gastric gavate once a day for 4 weeks. At the end of thefollow-up point, all the indexes described in the first part were detected again.In addition, the concentration of plasma and non-infarcted myocardial tissueAng II were measured with Radioimmunoassays; Cardiac fibrosis wasdisplayed by VG staining and collagen density was measured using imageanalytic system; The expression of δ-pkc protein in remote non-infarctedmyocardium were evaluated by immunohischemistry. At the same time, weused Sham 28d group and AMI 28d group as controls. Results (1)Sham-operated rats showed low rates of myocardialapoptosis (0.3%) and little change in hemodynamic parameters and cardiacmorphological parameters;(2)Myocardial apoptosis occurred both in theborder zones of infarcted myocardium and in the remote non-infarctedmyocardium. 24h after infarction, the MAI in the infracted areas markedlyincreased (2.1%) and peaked at 3d(7.6%) , then decreased gradually to 0.8% at4w in the border zones. It rised gradually from 0.3% at 24h to 0.8% at 4w inthe remote non-infarcted myocardium;(3)In the border zones, the expressionof Bax protein significantly increased at 24h after AMI, peake...
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