Open AccessAndrographolide inhibits arrhythmias and is cardioprotective in rabbits
Author(s) -
Meng-Liu Zeng,
Wentao Jiang,
Yan Tian,
Hao Jiang,
Zhijun Cao,
Zhi-Pei Liu,
Chen Fu,
Peihua Zhang,
Jing Ma
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.18051
Subject(s) - andrographolide , aconitine , afterdepolarization , medicine , pharmacology , in vivo , electrophysiology , myocyte , patch clamp , depolarization , cardiology , repolarization , chemistry , biology , microbiology and biotechnology
Andrographolide has a protective effect on the cardiovascular system. To study its cardic-electrophysiological effects, action potentials and voltage-gated Na + (I Na ), Ca 2+ (I CaL ), and K + (I K1 , I Kr , I to and I Kur ) currents were recorded using whole-cell patch clamp and current clamp techniques. Additionally, the effects of andrographolide on aconitine-induced arrhythmias were assessed on electrocardiograms in vivo . We found that andrographolide shortened action potential duration and reduced maximum upstroke velocity in rabbit left ventricular and left atrial myocytes. Andrographolide attenuated rate-dependence of action potential duration, and reduced or abolished delayed afterdepolarizations and triggered activities induced by isoproterenol (1 μM) and high calcium ([Ca 2+ ] o =3.6 mM) in left ventricular myocytes. Andrographolide also concentration-dependently inhibited I Na and I CaL , but had no effect on I to , I Kur , I K1 , or I Kr in rabbit left ventricular and left atrial myocytes. Andrographolide treatment increased the time and dosage thresholds of aconitine-induced arrhythmias, and reduced arrhythmia incidence and mortality in rabbits. Our results indicate that andrographolide inhibits cellular arrhythmias (delayed afterdepolarizations and triggered activities) and aconitine-induced arrhythmias in vivo , and these effects result from I Na and I CaL inhibition. Andrographolide may be useful as a class I and IV antiarrhythmic therapeutic.