| Studies have demonstrated that left ventricular remodeling in post-infarction is a very important affective factor in heart failure, even cardiac sudden death. RAS plays an important role in LV remodeling after AMI. Preventing and improving LV remodeling after AMI has become a focus in research areas of cardial vascular disease. Clinical trials and animal experiments suggested that ACEI reduced the post-MI cardiac remodeling, but the phenomenon of " Aldosterone escape" caused by ACEI during the treatment of heart failure have showed the limited effect of ACEI.Aldosterone has physiological effect on heart, independent angiotensin completely. Aldosterone promotes cardiac fibroblasts to produce collagen. In hypertension rats with aldosteronism, the synthesis of cardiac collagen increased, and so aldosterone plays an important role in the information and development of cardiac fibrosis. More recently, investigation suggested that aldosterone might be synthesised in myocardium tissue, cardiac Ald level significantly raised in the non-infracted areas of left ventricular in post-infarction, and accompanied with collagen proliferation. In 1999, RALES proved that antagonism of aldosterone had showed significant effect in the treatment of patient with CHF, mortality of CHF was reduced by 30 percent, and the mechanism of survival benefit was related to inhibited cardiac fibrosis by spironolactone. Thus, we hypothesize that antagonism of aldosterone may be contribute to reducing cardiac reactive fibrosis, inhibiting LV post-infarction remodeling, improving systolic and diastolic function. So far, it is still unclear how the effects of antagonism of aldosterone prevent left ventricular remodeling , and there is a dispute in Ang II type 2 receptor inhibiting left ventricular remodeling in post-infarction. This study investigated the effects of the aldosterone receptor antagonism- spironolactone and AT1 receptor blocker-losartan on ventricular remodeling and cardiac collagen proliferation in rats with left ventricular dysfunction after myocardial infarction.This experimental animals were healthy SD rats weighting 230-290g with male , which were bought from HeBei Medical University Experimental Animal Center, and were qualified for experiments.This study included four parts, as flows:Part I Effects of Spironolactone, Losartan and Combination therapy on LV remodeling in post myocardial infraction.Methods and Results Materials and Methods : left ventricular infarct in rats was produced by ligation of the left anterior descending coronary artery. After 48 hours , 240 rats in AMI were randomly divided into non-infarcted group and treatment group.①AMI group (water, 2ml·d-1 in drinking, n=12),②Spironolactone group (Spi, spironolactone 20mg· kg-1·d-1 in drinking, n=12),③Losartan group (Los, losartan 50mg·kg-1·d-1),④Combination group (SL, spironolactone 20mg· kg-1· d-1 + 50mg·kg-1·d-1 , n =12),⑤ Sham group(water, 2ml·d-1,n=12). Hemodynamic and ventricular weight parameters were measured at 2,4,6 weeks.2. Results: Changes of hemodynamic parameters.①Changes of blood: In comparison with AMI group, AOSP lowered 13.7%, 19.3% and 16.3% respectively ( P<0.05, P<0.01, P<0.01, respectively ) at 2,4,6 weeks and AODP lowered 12.2%, 8.3% respectively (all P<0.05) at 4, 6 week in Los groups. In comparison with AMI groups , AOSP and AODP had no significant difference in Spi groups (all P>0.05).② In comparison with AMI group, LVSP increased 7.2%(P<0.05) at 6 week, LVEDP lowered 24.9% and 22.1% respectively( all P<0.05) in Spi groups, LVSP increased 9.3%,14.5% and 16.4% respectively( P<0.05, P<0.01, respectively ) and LVEDP lowered 25%,29.4% and 26.7% respectively( P<0.05, P<0.01, P<0.01, respectively ) at 2, 4, 6 week in Los groups. LVSP was significantly higher at 4, 6 weeks (all P<0.01) and LVEDP was lower at 6 weeks (P<0.05) in Los groups than in Spi groups. In comparison with Spi groups, LVSP raised 17.6% and 16.4% respectively(all P<0.05) and LVEDP lowered 12.8% and 38.8% respectively(P<0.05,...
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