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Objective To observe the effects of granulocyte colony stimulating factor (G-CSF) on electrophysiological properties of post-infarct ventricles.Methods Sixty-seven survival Wistar rats were divided into 4 groups:Sham group,Control group,MI early G-CSF group (E-G) and MI delay G-CSF group (D-G) after ligation of the left coronary artery as myocardial infarction model.Monophasic action potential(MAP) was recorded by absorption electrode in ex vivo perfused rat hearts.Effective refractive period(ERP),sinus cardiac length (SCL),action potential amplitude (APA),maximal depolariged (Vmax),ventricular fibrillation threshold(VFF) and ventricular fibrillation duration(VFD) were measured.Results The electrophysiological parameters (SCL,VFT,VFD,APA,ERP/MAP90,dispersion of ERP and MAP90) of the E-G group were improved significantly (all P ＜ 0.05) at day 7 post MI.Improvement in SCL,dispersion of ERP and MAP 90 were found in the D-G group as well at day 7 post MI (all P ＜ 0.05).Substained improvement in electrophysiological parameters were found in the E-G group at 3 months after MI (P ＜0.05).Besides SCL,APA,Vmax and dispersion of MAP90,all other parameters in the D-G group were similar to that of the control group with no statistical significance and even had a tendency of deterioration in ERP and MAP90 3 months after MI.Conclusion G-CSF intervention could improve electrophysiological properties of ischemic ventricles.Early G-CSF intervention showed better outcomes compared to delay G-CSF intervention on electrical remodeling ischemia myocardiumwhich may have effect on reducing the development of ventricular arrhythmia.
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BACKGROUND:Ventricular arrhythmia (VA) is one of the most common complications of myocardial infarction (MI), and ventricular tachycardia and fibrillation are the main causes for sudden cardiac death. This study aimed to explore the effect of ramipril on the occurrence of VA and its mechanism after MI in rabbits. METHODS:Twenty-four New Zealand rabbits purchased from the Wuhan Laboratory Animal Research Center were divided into three groups:sham-operated (SHAM) group (n=8), MI group (n=8) and MI with ramipril (RAM) group (n=8). Rabbits in the SHAM group received a median sternotomy without ligation of the left ventricular coronary artery. Rabbits in the MI and RAM groups received a median sternotomy followed by ligation of the left coronary artery. The successful anterior MI was confirmed by elevation of the ST segment with more than 0.2 mV in lead II and III. After MI, rabbits in the RAM group were fed with intragastric ramipril (1 mg/kg per day ) for 12 weeks. Before and 12 weeks after MI in the three groups, ventricular tachycardia or fibrillation (VT/VF) episodes and MAP in cadiocytes of the epicardium, mid-myocardium and endocardium were recorded by a multichannel physiograph. Student'st test and ANOVA were used for statistical analysis. RESULTS:VT/VF episodes were decreased more markedly in the RAM group than in the MI group after 12 weeks (2.6±0.8 vs. 12.4±2.9,P<0.05). Twelve weeks after MI, the duration of repolarization for 90％ (APD90) of three-tier ventricular myocytes in the MI group was longer than that before MI (258.2±21.1 vs. 230.1±23.2, 278.0±23.8 vs. 245.8±25.4, 242.6±22.7 vs. 227.0±21.7,P<0.05). However, the APD90 was not significantly different at 12 weeks before and after MI in the RAM group (P>0.05). Moreover, the transmural dispersion of repolarization (TDR) was increased more markedly 12 weeks after MI in the MI group than in the SHAM and RAM groups (36.2±10.2 vs. 18.7±6.2, 24.9±8.7,P<0.05). But the TDR was not significantly different between the RAM and SHAM groups (18.7±6.2 vs. 24.9±8.7,P>0.05). CONCLUSION:Ramipril may reduce the incidence of malignant ventricular arrhythmia via improvement of transmembrance repolarization heterogeneity after MI.
ABSTRACT
Objective To determine whether specific angiotensin-conventing enzyme inhibitor with ramipril would affect ventricular arrhythmia generation in rabbits after myocardial infarction and discuss the mechanism of its antiarrhymic efficacy.MethodsTwenty-four New Zealand rabbits (Wuhan Laboratory Animal Research Center) were separated into 3 groups:sham-operated (SHAM) group (n =8 ),myocardial infraction (MI) group ( n =8) and myocardial infraction with ramipril (RAM) group ( n =8).SHAM group received a median sternotomy without left ventricular coronary artery ligation.MI and RAM groups' rabbits received a median sternotomy followed by left coronary artery ligation. The successful anterior MI was confirmed by elevation of the ST segment with more than 0.2 mV in lead Ⅱ and Ⅲ.After MI,RAM group rabbits were fed with ramipril [ 1mg/ ( kg · d) ]by intragastric administration for 12 weeks.Before and after MI 12 weeks in three groups.Ventricular tachycardia or fibrillation episodes and the monophasic actionpotential duration in epicardium,mid-myocardium and endocardium cadiocytes were recorded.The statistical technique was t-test and ANOVA.Results Ventricular tachycardia or fibrillation episodes were markedly decreased in RAM group than that in MI group after 12 weeks [ (2.6 ± 0.8) vs.(12.4 ± 2.9),P ＜0.05 ].After MI 12 weeks,the action potential duration of repolarization 90％ (APD90) of three-tier ventricular myocytes in MI group was prolonged than that before MI [ (258.2 ±21.1 ) vs.(230.1 ±23.2),( 278.0±23.8 ) vs.(245.8±25.4),(242.6±22.7) vs.(227.0±21.7),P＜0.05]; however,it was not significant difference between before and after MI 12w in RAM group (P ＞ 0.05 ).Moreover,the transmural dispersion of repolarization(TDR) was markedly increased after MI 12w in MI group than in SHAM and RAM group [ (36.2 ± 10.2 ) vs.( 18.7 ± 6.2 ),(24.9 ± 8.7 ),P ＜ 0.05 ]; but the TDR was not significant difference between RAM and SHAM group ( 18.7 ± 6.2 ) vs.( 24.9 ± 8.7 ),P ＞ 0.05].ConclusionsRamipril significantly reduced the malignant arrhythmia incidence in rabbits after MI.Mended the abnormal TDR was the mechanism for ramipril to therapy.