Effects of aldosterone blockade on collegen remodeling in non-infarcted myocardium after myocardial infarction

Objective To investigate the effects of aldosterone blockade on collegen remodeling in myocardial infarcted(MI)rats.Methods 45 rats that survived 24 hours after ligation of left anterior descending coronary artery were randomly divided into two groups:MI-saline group(n=22,5 ml/d)and MI-spironolacton(n=23,20 mg/kg·d).Sham operation group(n=15)was selected as non-infarction control.6 weeks after drug therapy by gastric gavage,hemodynamics and left ventricular function were measured with catheterization,interstitial fibrosis infiltration was evaluated with histological methods,collagen was measured by colorimetric method,type Ⅰ and type Ⅲ collagen were analyzed by immunohistochemical method,mRNA expression of type Ⅰ and type Ⅲ collagen was measured by reverse transcriptase-polymerase chain reaction(RT-PCR).Results ①Compared with the sham operation group,rats in MI group showed marked interstitial fibrosis infiltration in non-infarction area,higher ventricular weight/body weight ratio,(P0.01,respectively).②Compared with the sham operation group,the synthesis of collagen was increased in non-infarcted myocardium.The ratio of type Ⅰ/Ⅲ collagen and the mRNA expression of type I and type III collagen were also increased(P0.05,P0.01).Spironolacton significantly decreased the synthesis of collagen,the ratio of type Ⅰ/Ⅲ collagen and the mRNA expression of type Ⅰ and type Ⅲ collagen in non-infarcted myocardium at 6 weeks after infarction(P0.05,P0.01).③All infarcted rats developed significant systolic and diastolic dysfunction,as indicated by decreased LVSP and ±dp/dtmax,as well as increased LVEDP(P0.01,respectively).Aldosterone blockade significantly prevented cardiac fibrosis and systolic and diastolic dysfunction(P0.01,respectively).Conclusion Aldosterone blockade prevents cardiac collagen remodeling in non-infarcted myocardium after MI.