Comparison of effects of different does of Losartan in prevention of left ventricular remodeling after acute myocardial infarction in rats

Objective To Compare the effects of different doses of Losartan in the prevention of left ventricular remodeling(LVRM)after acute myocardial infarction(AMI)in the rats,and to evaluate the dose-effect relation,and to compare with enalapril.Methods Sham-operated(n=12)were selected randomly to serve as non-infarction controls.AMI were made by ligating left coronary artery in female Wistar rats.48 hours after the procedure,the 123 surviving rats wre randomly divided into five groups of AMI controls and high-,middle-and low-dose Losartan and enalapril.Losartan and enalapril were delivered by direct gastric gavage.After 3 weeks of medical therapy,hemodynamic studies were performed in each group,and the rat heart were then fixed,and pathologic analysis were performed.Complete experimental data obtained in 64 rats were analyzed,comprising of sham-operated group(n=9),AMI controls(n=8),high-dose Losartan group(n=13),middle-dose Losartan group(n=13),low-dose Losartan group(n=11),enalapril group(n=10).Results There were no significant differences among the five AMI groups in MI size around 44.5%~46.8%(all P0.05).Compared with sham-operated rats,the left ventricular end diastolic pressure(LVEDP),absolute and relative weight(LVAW and LVRW),expansion index(EI),remodeling index(RI)in AMI group were all significantly increased(P0.05~0.001),thinning ratio(TR)was significantly decreased(P0.05~0.001),indicating that LVRM occurred after AMI.The maximun left ventricular pressure rising and dropping rates(±dp/dtmax)were all significantly reduced in AMI group(all P0.001).Compared with the AMI group,LVEDP,LVAW,LVRW,EI and RI were all significantly decreased in all four treatment groups(P0.05~0.001),TR were all significantly increased(P0.05~0.001),and the LVEDP,EI,TR,RI and-dp/dtmax were all more significant in high-and middle-dose than in low-dose Losartan group(P0.05).Conclusion High,middle and low dose of Losartan are all effective in preventing left ventricular remodeling after AMI in rats,with high and middle dose of Losartan being more effective.