Effects of icariin on ventricular arrhythmia induced by congestive heart failure in rabbit in vivo and its electrophysiological mechanisms(PDF)
《中国医学物理学杂志》[ISSN:1005-202X/CN:44-1351/R]
- Issue:
- 2020年第3期
- Page:
- 361-367
- Research Field:
- 医学生物物理
- Publishing date:
Info
- Title:
- Effects of icariin on ventricular arrhythmia induced by congestive heart failure in rabbit in vivo and its electrophysiological mechanisms
- Author(s):
- WANG Jingjing; DONG Wei; JIANG Bo; LI Dandan; ZHANG Wei; WANG Jing; MU Yang; CHEN Si; LI Yang; CHEN Yundai
- Department of Cardiology, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Keywords:
- Keywords: congestive heart failure; icariin; ventricular arrhythmia; L-type calcium current
- PACS:
- R331.31
- DOI:
- DOI:10.3969/j.issn.1005-202X.2020.03.020
- Abstract:
- Abstract: Objective To investigate the effects of icariin (ICA) on ventricular arrhythmias (VA) induced by congestive heart failure (CHF) in rabbits in vivo and discuss its electrophysiological mechanism. Methods Healthy New Zealand male rabbits were divided into 3 groups, namely control group, CHF group and CHF+ICA group (ICA group). The CHF models were induced by isoproterenol injection (0.3 mg/kg/d for 3 weeks) via the ear vein; and whether the CHF models were established successfully was determined by clinical symptoms, left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in M-type echocardiogram, and heart rate and QT interval in Ⅱ-lead electrocardiogram (ECG). Some main electrophysiological parameters in 3 groups were recorded, such as maximum upstroke velocity (Maxdv/dt) of action potential, action potential duration at 20%, 50% and 90% repolarization (APD20, APD50 and APD90) from the recording of monophasic action potential (MAP) of ventricular muscle, and the ventricular effective refractory period (ERP150) with 150 ms of basic cycle length detected by programmed electrical stimulation and its dispersion (dERP150), and the inducibility and duration of VA detected by Burst-pacing. The L-type calcium current (ICa-L) and its current-voltage (I-V) curve were recorded by whole-cell patch clamp technique in enzymatically dissociated single ventricular myocyte in 3 groups. Results When the rabbits for the establishment of CHF model presented with clinical symptoms, such as emaciation, weakness, tachypnea, and muscle atrophy, and the LVEF and LVFS of the rabbits were obviously decreased, and left?ventricular?end-diastolic?internal?diameter was enlarged as well as interventricular septal thickness at diastole was attenuated (all P<0.01), and heart rate significantly dropped (P<0.05), and PR and QT interval were markedly lengthened (all P<0.01), and ST segment was upward (P<0.05), it was suggested that the CHF models were established successfully. Compared with CHF group, the administration of ICA not only significantly increased the action potential amplitude of ventricular tissues and Maxdv/dt, but also shorten APD10, APD20, APD50 and APD90 (all P<0.01). Moreover, the ERP150 and dERP150 of ventricular tissues as well as basic cycle length of induced VA were notably shortened. The induction rate of VA was significantly decreased with the administration of ICA (P<0.01). Finally, with voltage clamp, the administration of ICA markedly decreased the ICa-L of ventricular myocytes in CHF models, and upward I-V curve; and when the clamping voltage was +10 mV, the peak value of ICa-L of ventricular myocytes were significantly decreased from (9.98±0.53) pA/pF in CHF group to (6.95±0.15) pA/pF in ICA group (P<0.01). Conclusion ICA might notably modify the electrical remodeling and decrease the susceptibility to VA induced by CHF, therefore realizing anti-ventricular arrhythmias in CHF rabbits. The mechanisms might attribute to that ICA can markedly decrease ICa-L, and prevent calcium overload and oscillations with ICA perfusion in ventricular myocytes of CHF rabbits.
Last Update: 2020-04-02