Andrographolide inhibits arrhythmias and is cardioprotective in rabbits

Abstract

Andrographolide has a protective effect on the cardiovascular system. To study its cardic-electrophysiological effects, action potentials and voltage-gated Na⁺ (I_Na), Ca²⁺ (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 ([Ca²⁺]_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.