The Effect Of Aldosterone Receptor Antagoniston Ventricular Remodeling After Acute Myocardial Infarction

Acute myocardial infarction, especially large transmural myocardial infarction may cause complicated changes of the structure in infarcted and non-infarcted myocardium areas, namely ventricular remodeling, which led to heart failure and influenced the ventricular function and survival prognosis furtherly. In recent years, there have been a lot of fundamental changes in philosophy about the treatment of congestive heart failure after acute myocardial infarction: from the short-term, hemodynamic, pharmacological measures to the long-term, neuroendocrine antagonistic strategy. Activation of the neuro- endocrine system is the most important factors of promotion to ventricular remodeling. The effects of excessive activation of the rennin-angiotensin-aldosterone system on the ventricular remodeling have been of a consensus. As a vital factor of the rennin-angiotensin-aldosterone system, aldosterone may play an important role in the development and progression of heart failure after acute myocardial infarction. The blood circulation is responsible for cardiac aldosterone which can also be produced by regional myocardium. Aldosterone may bond to the cardiac aldosterone receptor and induce cardiovascular damage, promote myocardial collagen deposition, myocardial fibrosis, apoptosis, as well as ventricular remodeling and endothelial dysfunction. And it also results in the increasing of mortality in patients. The pathophysiological role of aldosterone in the process of heart failure as well as the phenomenon of aldosterone escape has definited that aldosterone receptor antagonist had an irreplaceable role in the modern treatment of heart failure. The impact of aldosterone receptor antagonist to ventricular remodeling after acute myocardial infarction has become a hot research of scholars. Application of aldosterone receptor antagonist may reduce the levels of plasma precollagen typeIII N terminal peptideserum (PIIINP) and hyaluronic acid (HA), attenuate the increased expression of genes of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP) and procollagen C-proteinase, decrease cardiac muscle cell apoptosis, inhibit the occurrence of myocardial fibrosis and development, suppress ventricular remodeling. Randomized aldactone evaluation study (RALES) illuminated that a long-term low-dose spironolactone for oral use in patients with chronic heart failure can seriously decrease the mortality rates of 30 percent. An analysis to a subgroup of RALES showed that spironolactone can inhibit cardiac fibrosis to improve left ventricular function. But the estrogen-like side effects of spironolactone restricted its application. The new aldosterone receptor antagonist eplerenone has much higher selectivition on the aldosterone receptor than spironolactone, and its hormonelike adverse reaction rate was significantly lower than spironolactone. The study of the eplerenone post-acute myocardial infarction heart failure efficacy and survival study (EPHESUS) indicated that low-dose eplerenone combined with the routine treatment may decrease the mortality by 17% of pump failure patients whose left ventricular ejection fraction≤0.40. More and more clinical trials and animal studies indicated that, aldosterone receptor antagonist combined with the routine treatment will be more effective in the inhibition of ventricular remodeling, improve left ventricular function, prevent and treat congestive heart failure after myocardial infarction.