Simvastatin Prevents Left Ventricular Systotic Dysfunction In Non-ischemic Rabbit's Heart Failure Mechanism Investigation

Objection:This study was to evaluate the effects of simvastatin on left ventricular function and sympathetic activity of Rabbits with heart failure,which were established by volume overload plus pressure overload,to investgate the possible mechanisms of cardioprotective effects of simvastatin in non-ischemic rabbits'heart failure.Method:(1)groups:30 rabbits were divided into 3 groups: sham operation group (n=10),heart failure group(n=10) and simvastatin given group(n=10).(2)models:sham operation group received sham operation as health control.In heart failure group and simvastatin given group,aortic regurgitation and coarctation of ascending aorta were operated in rabbits. In simvastatin given group,rabbits were given simvastatin 10mg?kg-1?d-1 after operation for 7 weeks.(3)heart function detection:heart function and haemodynamics were detected by echocaddiography and catheterization, while BNP levels were measured by euzymelinked immunosorbent assay(ELISA).(4)sympathetic activity analysis: ELISA was used to evaluate epinephrina(EPI) and noradrenaline(NE) levels.Western blot analysed protein kinase A(PKA),phospholamban(PLB) and phosphorylation of phospholamban at 16th serine(Ser16-P-PLB).Results:(1)heart function comparison:compared with sham-operated rabbits, LVEDP (mmHg:-7±4.61 vs 24.6±6.73) and BNP (pmol/ml: 4.41±0.94 vs 24.40±4.78) of congestive heart failure (CHF) rabbits were significantly increased (P<0.05); FS(%:38.23±3.51 vs 17.42±3.43) and EF (%:72.76±4.85 vs 47.80±6.05)were significantly decreased(P<0.05). Compared with CHF rabbits,in rabbits received treatment of simvastatin, LVEDP(mmHg:24.6±6.73 vs-2±4.57) and BNP(pmol/ml:24.40±4.78 vs 8.48±1.08)were significantly decreased(P<0.05), while FS(%:17.42±3.43 vs 34.16±2.27) and EF(%:47.8±6.05 vs 63.51±4.34) were significantly increased(P<0.05).(2)sympathetic activity comparison: compared with sham- operated rabbits, HR(bpm:223±21.91 vs 268±16.73),EPI(pg/ml:8.16±1.45 vs 25.40±4.78),NE(pg/ml:86.14±12.24 vs 173.04±39.15)and protein expressions of PKA(RPKA/actin:0.38±0.12 vs 0.88±0.15) and Ser16-P-PLB(Rser16-P-PLB/actin:0.44±0.14 vs 0.86±0.16) were significantly increased(P<0.05). Compared with CHF rabbits,in rabbits received treatment of simvastatin, HR(bpm:268±16.70 vs 237±21.32),EP(Ipg/ml:25.40±4.78 vs 13.97±3.59),NE(pg/ml:173.04±39.15 vs 121.72±15.84)and protein expressions of PKA(RPKA/actin:0.88±0.15 vs 10.43±0.11) and Ser16-P-PLB (Rser16-P-PLB/actin:0.86±0.16 vs 0.47±0.14) were significantly decreased(P<0.05).Conclusion:(1)The left ventricular function is decreased while the sympathetic activity is increased of rabbits with volume overload plus pressure overload;(2) Simvastatin can inhibit over-activated sympathetic nervous system, prevents left ventricular systotic dysfunction and ventriculus reconstitution in heart failure rabbits with volnme overload plus pressure overload;(3)Simvastatin can inhibit the catecholamine-PKA-phosphorylation of PLB channel,which may means simvastatin can anti sympathesis;(4)The mechnism of simvastatin delaies left ventricular systolic dysfunction in non-ischemic rabbit's heart failure maybe due to inhibit sympathetic overstimulation.