Objective To investigate the therapeutic effects of recombinant adeno-associated virual gene serotype 1(rAAV1) mediated transfer of sarcoplasmic reticulum Ca2+ ATPase(SERCA2a) on beagle dogs with heart failure(HF).Methods The chronic HF model was reproduced in beagle dogs by giving rapid right ventricular pacing(230 beats/min) for 30 days.A reduced rate(180 beats/min)was continued for another 30 days.Sixteen beagle dogs were divided into four groups(4 each): control group,HF group,HF+EGFP group and HF+SERCA2a group.After rapid pacing for 30 days,rAAV1-EGFP(1?1012vg/ml) and rAAV1-SERCA2a(1?1012vg/ml) were respectively delivered via intramyocardial routes,while no treatment was given to the animals in both control and HF groups.At the end of the study,haemodynamics,echocardiography and the protein expression of SRCA2a were measured respectively.The apoptosis index of cardiac myocyte was evaluated by TUNEL.Bax expression was assessed by immunohistochemistry.Results After gene transfer of SERCA2a in HF beagle dogs for 30 days,the heart function was improved along with an increase in SERCA2a expression.Left ventricular systolic function was significantly increased,including the left ventricular systolic pressure(LVSP),left ventricular maximal rate of pressure rise(LV+dp/dtmax),left ventricular maximal rate of pressure decline(LV-dp/dtmax,P

Objective To explore the effect of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) overexpression on neuroendocrine system in chronic heart failure beagles. Methods The cardiac contraction function of chronic heart failure beagles were assessed by echocardiography before and after SERCA2a gene transduction. Radiation immune method was used to test the serum level of neuroendocrine factors such as Angiotensin Ⅱ, atrial natriuretic peptide, endothelin-1 and TNF-α, IL-6. Results The cardiac contraction function of chronic heart failure beagles improved greatly (P<0.05), and the serum levels of neuroendocrine factors significantly reduced after SERCA2a overexpression (P<0.05). Conclusion The vicious circle of neuroendocrine system may be blocked partially by SERCA2a overexpression.

29.3% decrease in ejection fraction).4 of 11 were used as heart failure group(HF,n=4).9 HF beagles were randomized to receive either a recombinant adeno-associated viral carrying the SERCA2a gene(HF+SERC A2a,n=5) or the reporter gene enhanced green fluorescent protein(HF+EGFP,n=4) by thoracotomy.All HF beagles paced by 180 beats/min in order to maintain failing state.Thirty days after infection,parameters of systolic and diastolic function were measured by doppler echocardiography and hemodynamic monitor in all beagles.RESULTS:At 30 days after gene transfer,symptoms of HF+SERCA2a dogs improved.Echocardiogram parameters were superior to those in HF+EGFP group(P

ObjectiveTo assess the safety of intramyocardium injection of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) to rescue chronic heart failure beagles. MethodsThe heart failure beagles were assessed with myocardium enzymology, cAMP content of myocardium, myocardial oxygen consumption, arrhythmia, systemic inflammation factors, and the function of liver and kidney after SERCA2a gene transferred. ResultsThere were no increase of cAMP content, no more arrhythmia, myocardial oxygen consumption, no apparente systemic inflammation, and no injures to hepatic and renal function. ConclusionOverexpression of SERCA2a by intramyocardium injection is relatively safe.