2-Methyithio-adenosine-5'-triphosphate inhibits ventricular arrhythmogenesis in rabbits with chronic heart failure
10.3760/cma.j.issn.0253-3758.2015.03.007
- VernacularTitle:2-甲硫基三磷酸腺苷可抑制兔慢性心力衰竭引起的室性心律失常
- Author:
Yi YANG
1
;
Wei LIU
;
Xiuhong LU
;
Yi YANG
;
Gui ZHANG
;
Jing HE
;
Chuan HU
Author Information
1. 武警广东医院老年病科
- Keywords:
Heart failure,congestive;
Arrhythmia;
2-MeSATP
- From:
Chinese Journal of Cardiology
2015;43(3):212-218
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects and related mechanisms of 2-methylthio-adenosine-5'-triphosphate (2-MeSATP),an important extracellular agonist that activates receptors for purine nucleotides (P2XR),on ventricular arrhythmias in rabbits with chronic heart failure (CHF).Methods The male New Zealand rabbits were divide into control (n =12),CHF (n =12) and CHF + 2-MeSATP groups(2-MeSATP,n =12).CHF was induced by isoproterenol injection (0.3 mg· kg-1 · d-1 for 3 weeks) and rabbits were observed 6 months later.The main cardioelectrophysiological parameters and ventricular arrhythmias were tested by recording monophasic action potential (MAP) with burst-pacing (BCL) in rabbits in vivo.The transient outward potassium current (Ito) was recorded via whole-cell patch clamp technique and the fluorescence intensity of intracellular free Ca2+ was detected with Flup-3/AM loading by the laser scanning confocal microscope in enzymatically dissociated single rabbet ventricular myocytes.Results CHF rabbits developed severely clinical CHF signs and symptoms,reduced left ventricular ejection fraction and fractional shortening as well as enlarged end-diastolic dimension.Compared with CHF group,APA and MaxdV/dt were significantly increased,while APD20,APD50 and APD90 were significantly reduced in 2-MeSATP group (all P ＜ 0.01).Moreover,2-MeSATP could obviously shorten BCL induced ventricular arrhythmias,and decrease deducibility and persistence time of ventricular arrhythmias with burst-pacing in 2-MeSATP group in vivo (all P ＜ 0.05).With voltage clamp model,2-MeSATP could significantly increase the current density of Ito in different command potential in CHF ventricular myocytes (all P ＜ 0.01).When holding potential was set at-50 mV and command potential was set at + 50 mV,the current densities of Ito increase was more significant in 2-MeSATP group than that in CHF group((11.79 ± 4.51) pA/pF vs.(7.94 ± 3.53) pA/pF,P ＜ 0.01).2-MeSATP could completely change the Ⅰ-Ⅴ curve upward without changing the Ⅰ-Ⅴ curve direction in CHF ventricular myocytes.The fluorescence intensities of intracellular free Ca2+ increase was more significant in 2-MeSATP group compared to CHF group ((1 291.98 ± 123.31) μmol/L vs.(793.59 ± 114.65) μmol/L,P ＜ 0.01).Conclusion 2-MeSATP as a potent agonist acting on P2XR could significantly shorten APD,increase heart rate and improve cardiac performance as well as decrease the susceptibility of ventricular arrhythmias in this rabbit CHF model.Our results suggest that Ito increase and sarcoplasmic reticulum uptake Ca2+ enhancement as well as dynamic balance of intracellular Ca2+ cycling sustenance might linked to the beneficial effects of 2-MeSATP in this CHF model.
