[Effects of recombined human neuregulin on the contractibility of cardiac muscles of rhesus monkeys with pacing-induced heart failure].
OBJECTIVE
To evaluate the effects of recombined human Neuregulin on the contractibility of cardiac muscles of Rhesus Monkeys with pacing-induced heart failure and to reveal the possible mechanisms involved.


METHODS
Twenty four rhesus monkeys were randomly divided into three groups (shame operated group, heart failure group and Neuregulin treated group), each with 8 monkeys. Heart failures were induced by rapid pacing (240 heartbeats/min). Daily intravenous injection of recombined human Neuregulin [3 microg/(kg x d)] and medical salt fluid were given to the monkeys for 10 days for the Neuregulin treated group and heart failure group respectively. Hemodynamic measurements such as peak positive rate of change in left ventricular blood pressure (+dP/dtmax) and left ventricular systolic, and end-diastolic blood pressures (LVSP and LVEDP) were compared between groups. The real-time quantitative RT-PCR was undertaken to detect the expression of myosin heavy chain mRNA in the left ventricular cardiac muscle.


RESULTS
The monkeys in the heart failure group had lower levels of +dP/dtmax and LVSP and higher levels of LVEDP than those in the shame operated group (P < 0.05). The monkeys in the Neuregulin treated group had higher levels of + dP/dtmax than those in the heart failure group (P < 0.05). Lower expression of alpha-myosin heavy chain mRNA in the heart failure group was found compared with the shame operated group and Neuregulin treated group (P < 0.05).


CONCLUSIONS
Recombined human Neuregulin can enhance the contractibility of cardiac muscles and relieve heart failure syndrome through reversing the falling of alpha-myosin heavy chain induced by rapid ventricular pacing.
Li
Jiang
J
National Chengdu Center for Safety Evaluation of Traditional Chinese Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Gu
Xing-hua
XH
Duan
Jia-chuan
JC
Zeng
Li
L
Li
You
Y
Wang
Li
L
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D020880:Neuregulins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D024723:Ventricular Myosins / Q000235:genetics
D020880:Neuregulins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D024723:Ventricular Myosins