Effects Of Carvedilol And Fosinopril Treatment On Left Ventricular Remodeling After Acute Myocardial Infarction In Rats

BACKGROUND The general process by which the left ventricular experiences changes in structure, shape and function after acute myocardial infarction is often referred as "left ventricular remodeling". Recently, it also involves the changes in myocardial cells and in both the quantity and quality of the extracellular matrix. A great deal of clinical and experimental studies indicate that left ventricular remodeling is the main reason of progressing left ventricular dysfunction and congestive heart failure after myocardial infarction and it is also the most important risk factor of late cardiac death. Therefore, the pathophysiologic process of left ventricular remodeling, and better treatment have been better appreciated recently.Both experimental and clinical studies indicated that early reperfusion of infarct-related artery may salvage the endocardial tissue and restore stuned myocardium in the infarct border zone, reduce infarct size and prevent infarct expansion. It is an efficient treatment in acute phase to prevent left ventricularremodeling after myocardial infarction. But patients with a patent infarct-artery also may undergo left ventricular remodeling. The efficacy of ACE inhibitors in reducing infarct size and attenuating left ventricular dilation after infarction was associated with improved survival. Treatment with b-blockers also reduces mortality and mortality among patients with myocardial infarction, but studies on the effect of b-blockers on remodeling after myocardial infarction have been little. In addition, detailed hemodynamic studies have not been performed to determine the long-time effect of b-blockers after myocardial infarction. AIM Therefore, the present study aimed to develop a rat model with left ventricular dysfunction after myocardial infarction, observe the effects of use of b-blocker-carvedilol and ACEI-fosinopril on hemodynamic function and left ventricular remodeling after myocardial infarction. By means of ligature of left anterior descending branches of coronary artery, the rat model of myocardial infarction were established. The ultrastructural organization were observed by electron microscope in different situations, including myocardial infarction , sham operation and treatment with carvedilol.METHODS Sixty rats with a model of myocardial infarction were randomly divided into nine groups . The rats of therapeutical group were treated with carvedilol injection (2mg/d intraperitoneal injection) and/or fosinopril (2g/L drinking water). Acute myocardial infarction (AMI) group did not receive drug treatment. The animals were sacrificed at 4 weeks and 8 weeks after coronary artery ligation. The levels of plasma angiotensin II and plasma aldosterone and left ventricle function were determined at different time. The collagen of type I and type III collagen of noninfarcted area were also assessed. RESULTS Compared with AMI group, the levels of plasma and myocardiumangiotensin II and plasma aldosterone in both carvedilol and fosinopril group decreased at the eighth week (P<0.05). In addition, carvedilol improved systolic and diastolic function (P<0.05). Compared with sham group, both collagen content and the ratio of type I/III collagen of noninfarcted area increased in AMI 4 and AMI 8 group (P<0.05). The hydroxyproline levels and the ratio of type I/III collagen significantly decreased after carvedilol and/or fosinopril treatment, compared with AMI group at 4 or 8 week (P<0.05). The mitochondria and other organellae injury in the AMI group was more serious than that in carvedilol group.CONCLUSIONS Carvedilol can improve cardiac function after myocardial infarction and has beneficial effect on left ventricular collagen remodeling. Fosinopril can significantly decrease the proliferation of myocardial extracellular matrix and relieve the myocardial injury. The myocardial cell apoptosis can be induced by myocardial infarction and be inhibited by carvedilol. Using Western-blot analysis, histochemical, MMP-2 gene expression, type I and type III collagen were anal...