| Background:Chronic heart failure (CHF) of children is the common ending of many heart diseases with various causes. In recent 10 years, researchers have gradually known that the essential mechanism of CHF is ventricular remodeling [1], its essence is the changes of cardiac myocytes and the matrix out of cytomembrane, including the losses of cardiac myocytes, maladative hypertrophy, deposition of collagen outside cytomembrane and fibrosis. And it shows the increases of myocardium weight and ventricular volume, the changes of ventricular formation, and the transformation of the matrix and collagen out of cytomembrane. At present, it's considered that the key of treatment of CHF is to suppress the neuroendocrine hormones and block the malignant cycles of ventricular remodeling. Recent data show that ventricular remodeling is transducted by chronic adrenergic system, and β1 adrenergic signal transduction7 pathway is the main pathway resulting in heart toxicity. Carvedilol, the third generation beta-adrenergic receptor blocker(β-ARB), has the effect of general β receptor blockage; it has been applied to adults already but its application to children has been rarely reported. Whether Carvedilol could prevent the ventricular remodeling of immature rats in the processes of CHF, and the mechanism of its effect are still unclear.Objective:To observe the effect of Carvedilol on occurrence and development of ventricular remodeling of immature rats in processes of CHF; and to discuss its mechanism from the points of view of the myocardial apoptosis, the expression ofbcl-2 and p53 genes of myocardial cells and oxidation stress.Materials and Methods:The model of CHF was established by gradually constricting the abdominal aorta of 5-month male Wistar rats, the survivals after operation were divided into two parts: prevention administration and treatment administration. ⑴Prevention administration: the animals were divided into sham group, control (CHF) group and small dosage, middle dosage and large dosage of Carvedilol groups. 24 hours after operation, Carvedilol was administered (twice a day), and yet the equivalent dosage of drinking water was administered to the animals of sham group and control group. Then observed the changes of body weight, fur skin and activity amount and so on every 7 days. 4 weeks later, after administration in the morning, we used the high frequency ultrasonography to detect ventricular bore, thickness of the ventricular walls, FS(%), and EF(%). Then detached right-side common carotid artery, connected eight tubers physiological recorder to record the hemodynamic data; And finally got the blood by using decapitation, detached the heart for pathological determination. ⑵Treatment administration: the animals were random divided into sham group, control (CHF) group and Carvedilol treatment group. Administration began at 4 weeks after operation, hemodynamic and pathological determinations were carried out by 8 weeks after operation. We respectively used terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and ABC immunohistochemical staining to detect the changes of apoptosis and protein expression of bcl-2 and p53 genes, chromatometry to detect the concentration of LPO, and radio-immunity assay to determine the activity of SOD in serum.Results:1．The mortality of immature rats after operation of constricting the abdominal aorta was 52 percents.2．The increase of body weight and the decrease of activity amount were affected by the deterioration of myocardial function in immature rats with CHF.3．It showed hemodynamic disorder, the increase of ventricular bore, hypertrophy and the deterioration of myocardial function in immature rats with CHF.4．In CHF immature rats, apoptosis index, the expression of p53 gene and the concentration of LPO in serum all increased; While both the expression of bcl-2 gene and the activity of SOD decreased.5．Carvedilol can improve the state of hemodynamics, suppress ventricular remodeling and improve t... |
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