Effect of carvedilol and Radix astragali on ryanodine receptor in heart failure in mice / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore change of ryanodine receptor (RyR) in junior mouse with heart failure (HF) and the effect of β-adrenoreceptor blocker and Radix astragali on RyR in HF in this experiment.</p><p><b>METHOD</b>The animal model of congestive heart failure was established by coarctation of abdominal aorta. Five weeks old mice were randomly divided into 4 groups: (1) HF group without treatment (n = 30); (2) HF group treated with carvedilol (n = 30); (3) HF group treated with carvedilol and Radix astragali(n = 30); (4) Sham-operated group (n = 30). Carvedilol and Radix astragali were administered through direct gastric gavage. After 4 weeks of treatment the high frequency ultrasound was performed. Myocardial sarcoplasmic reticulum (SR) was fractionated with ultra centrifugation. The time courses of Ca(2+) uptake and leak were determined by fluorescent spectrophotometry. The levels of expression of RyR2 in the 4 groups were detected by semi-quantitative reverse transcription-polymerase chain reaction.</p><p><b>RESULT</b>Compared with the sham-operated group, left ventricular diastolic dimension (LVEDD) (P < 0.05), left ventricular systolic dimension (LVESD), interventricular septal thickness at end-diastole (IVSTd), interventricular septal thickness at end-systole (IVSTs), left ventricular posterior wall thickness at end-diastole (LVPWTd), and left ventricular posterior wall thickness at endsystole (LVPWTs) were all significantly increased (P < 0.01), ejection fraction (EF)(%) (HF group without treatment 51.60 ± 1.15, HF treated with carvedilol 72.06 ± 1.39, HF treated with carvedilol and Radix astragali 79.06 ± 1.09, sham-operated group 85.86 ± 1.45) and fractional shortening (FS) (HF group without treatment 44.55 ± 1.20, HF treated with carvedilol 44.55 ± 1.20, HF treated with carvedilol and Radix astragali 53.58 ± 1.30, sham-operated group 59.03 ± 1.67) were decreased (P < 0.01) in HF group without treatment. LVEDD (P < 0.05), LVESD, IVSTd, IVSTs, LVPWTd and LVPWTs were all significantly decreased (P < 0.01), EF and FS were increased (P < 0.01) in the cases with HF treated with carvedilol and carvedilol and Radix astragali when compared with HF group without treatment. EF and FS were much more increased in the group treated with carvedilol and Radix astragali than in those treated with carvedilol (P < 0.05). After adding thapsigargin to the buffer including SR of the four groups, there were fewer Ca(2+) leak (%) in sham-operated group (11.5 ± 4.3), HF group treated with carvedilol (15.6 ± 5.8) and treated with carvedilol and Radix astragali (13.6 ± 4.8) than that of HF group without treatment (65.6 ± 6.2) (P < 0.01), while after adding FK506 and thapsigargin together to the buffer including SR of four groups, there were marked Ca(2+) leak in sham-operated group (60.6 ± 7.8), HF group treated with carvedilol (66.2 ± 4.5)and those treated with carvedilol and Radix astragali (70.2 ± 5.5, P < 0.01). However, there was no additional increase in Ca(2+) leak in HF group (67.3 ± 7.5) compared with that of the group where only thapsigargin was added (P > 0.05). The levels of expression of RyR2 were significantly decreased in HF group and increased in the group treated with carvedilol and the group treated with carvedilol and Radix astragali.</p><p><b>CONCLUSION</b>There was more cardiac Ca(2+) leak and the expression of RyR2 mRNA decreased in HF. Carvedilol and Radix astragali can increase expression of RyR2 mRNA and inhibit Ca(2+) leak by restoring the binding of FKBP12.6 back to RyR in HF to improve cardiac function and prevent left ventricle from remodeling.</p>

Preliminary study on the effect of carvedilol on children with primary endocardial fibroelastosis / 中华儿科杂志

<p><b>OBJECTIVE</b>Endocardial fibroelastosis (EFE), a common pediatric cardiovascular disease, often results in chronic heart failure (CHF) and death. Clinical trials have shown that the regimen of combining beta-adrenoreceptor blocker with traditional medicines against CHF can improve left ventricular function and prevent the ventricle from remodeling in patients with CHF. The present study aimed to observe the effect of carvedilol on concentration of plasma brain-type natriuretic peptide (BNP), and safety in children with EFE.</p><p><b>METHODS</b>Twenty-one children with EFE were randomly divided into two groups: (1) treated with traditional regimen (digoxin, prednisone and/or diuretics) (n = 10); (2) treated with carvedilol plus traditional regimen (n = 11). Measurement of plasma concentration of BNP by ELISA, cardiac function by ultrasound were performed before and after 6 months of treatment. The changes in clinical symptom, heart rate, heart function, side effect and maximal tolerance dose after treatment with carvedilol were observed.</p><p><b>RESULTS</b>Plasma concentration of BNP was much higher in the group of patients with EFE [(865 +/- 702) ng/L] than that of control group [(154 +/- 78) ng/L] (P < 0.01), and there was a positive correlation between plasma concentration of BNP and cardiac function classification, and cardiac function grades II, III, and IV corresponded to plasma concentration of BNP (286 +/- 125) ng/L, (437 +/- 386) ng/L, (1673 +/- 859) ng/L respectively in children with EFE. Compared with the group treated with traditional medicines, plasma concentration of BNP [(403 +/- 216) ng/L vs. (219 +/- 87) ng/L] significantly decreased, the clinical symptom was significantly improved, cardio-thoracic ratio (CTR) (0.60 +/- 0.05 vs. 0.54 +/- 0.06) (P < 0.05) and heart rate [(115 +/- 20) bpm vs. (90 +/- 14) bpm] (P < 0.01) decreased, ejection fraction (EF) (46.6% +/- 13.4% vs. 54.5% +/- 12.9%), fractional shortening (21.6% +/- 8.1% vs. 24.1% +/- 7.5%), mean velocity of circumferential fiber shortening [(0.8 +/- 0.5) cir/s vs. (0.9 +/- 0.4) cir/s] were significantly increased (P < 0.01), left ventricular end-systolic dimension [(34.0 +/- 8.6) mm vs. (32.2 +/- 9.1) mm] (P < 0.05), left ventricular mass [(65.9 +/- 34.1) g vs. (65.9 +/- 34.1) g], interventricular septal thickness at end-systole [(6.0 +/- 1.0) mm vs (5.5 +/- 1.1) mm] were notably decreased (P < 0.01) after treatment with carvedilol.</p><p><b>CONCLUSION</b>These data indicated that plasma concentration of BNP significantly increased in children with EFE, carvedilol can decrease plasma concentration of BNP, inhibit the remodeling of ventricle, significantly improve the cardiac function in children with EFE. Carvedilol is effective and safe in treatment of children with EFE.</p>

Expression of connective tissue growth factor in cardiomyocyte of young rats with heart failure and benazepril intervention / 中华儿科杂志

<p><b>OBJECTIVES</b>Ventricular remodeling is an important pathologic progress in almost all end stage heart failure (HF), and it is characterized by ventricular thickening and cardiac fibrosis with poor prognosis. The connective tissue growth factor (CTGF), a new growth factor with multi-function, has an important role in fibrosis of tissue and organs. It has been demonstrated that angiotensin-converting enzyme inhibitor (ACEI) can prevent the development of cardiomyocyte from remodeling and improve cardiac function. Researchers try to test the hypothesis that cardiac function improvement attributable to ACEI is associated with inhibiting expression of CTGF in patients with HF. The aim of this study was to observe changes in CTGF expression in cardiomyocyte of young rats with HF and effect of benazepril on CTGF.</p><p><b>METHODS</b>The animal model of HF was established by constriction of abdominal aorta. Five weeks old rats were randomly divided into 3 groups after 6 weeks of operation: (1) HF group without treatment (n = 15); (2) HF group where rats were treated with benazepril (n = 15); (3) sham-operated group (n = 15) where rats were administered benazepril through direct gastric gavage. After 4 weeks of treatment, the high frequency ultrasound was performed. The expression of CTGF was detected by immunohistochemistry and semi-quantative reverse transcription-polymerase chain reaction.</p><p><b>RESULTS</b>Compared with the sham-operated group, left ventricular diastolic dimension (LVEDD), left ventricular systolic dimension (LVESD), interventricular septal thickness at end-diastole (IVSTd), interventricular septal thickness at end-systole (IVSTs), left ventricular posterior wall thickness at end-diastole (LVPWTd), left ventricular posterior wall thickness at end-systole (LVPWTs), left ventricular relative weight (LVRW), and right ventricular relative weight (RVRW) were all increased (P < 0.01), but ejection fraction (EF) and fractional shortening (FS) were decreased (P < 0.01). CTGF positive cells and expression of CTGF mRNA (0.609 +/- 0.065 vs 0.117 +/- 0.011, P < 0.01) were increased in HF group without treatment. LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW and RVRW were all decreased (P < 0.01), but FS and EF were increased (P < 0.01) in cases of HF treated with benazepril when compared with HF group without treatment. LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW and RVRW were higher (P < 0.01), EF and FS were lower (P < 0.01), CTGF positive cells and expression of CTGF mRNA were higher (P < 0.01) in HF group treated with benazepril than those of sham-operated group.</p><p><b>CONCLUSION</b>The expression of CTGF was increased in the cardiomyocyte of young rats with HF and benazepril could prevent left ventricular from remodeling partly and improve cardiac function by inhibiting the expression of CTGF in cardiomyocyte in cases of HF.</p>

Study on Effect of Carvedilol on Children with Endocardial Fibroelastosis / 实用儿科临床杂志

Objective To observe the clinical effect and security of carvedilol on children with endocardial fibroelastosis(EFE).Methods Eighteen children with EFE treatment with carvedilol.The improvement of clinical symptom,heart rate,heart function,side effect and maximal tolerance dose after treatment with carvedilol were observed.Results The clinical symptom was obviously improved;eiection fraction(EF),fractional shortening(FS),mean velocity of circumferential fiber(Mvcf)were significantly increased,left ventricular end-systolic dimension(LVDS),left ventricular mass(LVmass),interventricular septal thickness(IVSs)were notably decreased after treatment with carvedilol.Conclusions The data indicates that carvedilol can significantly reduce left ventricular diastolic dimension(LVDD),IVSs,and LVmass,inhibit the remodeling of ventricle,significantly elevate the heart function of EFE.So carvedilol is benefit and security on children with EFE.

Effect of carvedilol on ryanodine receptor in heart failure / 中华儿科杂志

<p><b>OBJECTIVE</b>The release of intracellular stores of Ca(2+) occurs virtually in all types of cells by a means of amplifying external signals that modulate intracellular signaling events. In cardiac myocytes, type 2 ryanodine receptor (RyR(2)) is activated during excitation-contraction (E-C) coupling by Ca(2+)-induced Ca(2+) release (CICR) triggered by Ca(2+) influx across the sarcolemma. The hyperadrenergic state of heart failure results in leaky RyR(2) channels attributable to PKA hyperphosphorylation and depletion of the stabilizing FK506 binding protein, FKBP12.6. Dysregulation of sarcoplasmic reticulum (SR) Ca(2+) release via RyR(2) could contribute to defects in Ca(2+) signaling in failing hearts. Researchers tested the hypothesis that improved cardiac muscle function attributable to beta-AR blockade is associated with restoration of normal RyR(2) channel function in patients with heart failure. The authors aimed to observe change of RyR in junior mouse with HF and the effect of beta-adrenoreceptor blocker on RyR in HF in this experiment.</p><p><b>METHODS</b>The animal model of congestive heart failure was established by constriction of abdominal aorta. Five weeks old mice were randomly divided into 3 groups: (1) HF group without treatment (n = 20); (2) HF group treated with carvedilol (n = 20); (3) Sham-operated group (n = 20). Carvedilol was administered through direct gastric gavage. After 4 weeks of treatment the high frequency ultrasound was performed. Myocardial SR was fractionated with velocity centrifugation. The time courses of Ca(2+) uptake and leak were determined by fluorescent spectrophotometr.</p><p><b>RESULTS</b>Compared with the sham-operated group, left ventricular diastolic dimension (LVEDD) (P < 0.05), left ventricular systolic dimension (LVESD), interventricular septal thickness at end-diastole (IVSTd), interventricular septal thickness at end-systole (IVSTs), left ventricular posterior wall thickness at end-diastole (LVPWTd), and left ventricular posterior wall thickness at end-systole (LVPWTs) were all significantly increased (P < 0.01). Ejection fraction (EF) and fractional shortening (FS) were decreased (P < 0.01) in HF group without treatment. LVEDD (P < 0.05), LVESD, IVSTd, IVSTs, LVPWTd and LVPWTs were all prominently decresed (P < 0.01). EF and FS were increased (P < 0.01) in cases of HF treated with carvedilol when compared with HF group without treatment. After adding thapsigargin to the buffer including SR of three groups, there were fewer Ca(2+) leak in sham-operated group and HF group treated with carvedilol than that of HF group without treatment (P < 0.01), while after adding FK506 and thapsigargin together to the buffer including SR of three groups, there were marked Ca(2+) leak in sham-operated group and HF group treated with carvedilol (P < 0.01). However, there was no additional increase in Ca(2+) leak in HF group compared with that of the group where only thapsigargin was added (P > 0.05).</p><p><b>CONCLUSION</b>There is more cardiac Ca(2+) leak in HF. Carvedilol can inhibite Ca(2+) leak by restoring the contactation of FKBP12.6 back to RyR in HF to improve cardiac function and prevent left ventricle from remodeling.</p>