Studies Of Losartan On Left Ventricular Remodeling After Acute Mycardial Infarction In Rats

Objective To compare the effects of high, middle, low doses and different terms of Losartan in the prevention of left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats, and to evaluate the dose-effect relation. Methods AMI were made by ligating left coronary artery in female Wistar rats. Forty-eight houres after the procedure, 158 surviviors were randomized to five groups of AMI controls, enalapril and high-,middle-and low-dose losartan (10mg-kg-1-d-1, 1.0mg-kg-1-d-1 and 0.1mg-kg-1-d-1). Sham- operated rats were selected randomly to serve as non-infarcttion controls. Then every group was divided to three term groups of 7, 14 and 21d. Losartan and enalapril were delivered by direct gastric gavage. After 7, 14 and 21d of treatment, hemodynamics studies were performed. And then the rat hearts were fixed and pathologic analysis was conducted in each groups. Complete experimental data were obtianed in 148 rats. Results The MI size on all AMI groups are 44.52 - 46.80 %. Compared with the sham-operated rats, the left ventricular end diastolic pressure (LVEDP) , absolute and relative weigt (LVAW and LVRW) in AMIgroup were all increased (all P<0.01) , The expansion index (EI) and remodeling index (RI) were all increased (P<0.01) . But the mining ratio (TR) was reduced (P<0.05) . Indicating LVRM had developed after AMI. Compared with AMI group, LVEDP, LVAW, LVRW, El and RI were all decreased in three losartan and enalapril groups(P<0.05-0.01). The reduction of LVEDP, LVAW, LVRW, El and RI was more significant in high-dose than low-dose losartan group (all P<0.05). The+dp/dt/LVSP were improved only in high-and middle-dose losartan groups (P<0.05-0.01). Conclusions High, middle and low dose of losartan and enalapril are all effectiv in preventing left ventricular remodeling after AMI in rats, with high dose losartan being more effective.Both high, middle dose losatan and enalapril can also improve LV systo-diastolic function, with low dose of losartan was found ineffective.