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 <i>in vivo</i>. 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 <i>in vivo</i>, and these effects result from I_Na and I_CaL inhibition. Andrographolide may be useful as a class I and IV antiarrhythmic therapeutic.