Effects of berberine on delayed afterdepolarizations in ventricular muscles in vitro and in vivo.
The effects of berberine on delayed afterdepolarizations in ventricular muscles in vitro and in vivo were investigated to help explain the mechanisms for its antiarrhythmic action. Berberine 3 mumol reduced the amplitude of delayed afterdepolarizations induced by ouabain or posthypoxic reoxygenation and abolished subsequent triggered activity in isolated guinea pig right ventricular papillary muscles. At 30 mumol, it decreased the incidence of delayed afterdepolarizations, associated with a further decrease in the amplitude of delayed afterdepolarizations. In rabbit left ventricular (LV) muscles in vivo, berberine 1 mg/kg intravenously (i.v.) decreased the amplitude of delayed afterdepolarizations evoked by ouabain and calcium gluconate from 9.6 +/- 1.9 to 6.8 +/- 0.8 mV and left stellate ganglion stimulation from 9.4 +/- 2.1 to 6.2 +/- 0.7 mV and blocked ventricular arrhythmias. After a 4-mg/kg i.v. bolus, the drug inhibited and even completely abolished development of delayed afterdepolarizations, yet still reduced maximal velocity of depolarization in isolated and in vivo ventricular muscles. Therefore, one of the important mechanisms for antiarrhythmic action of berberine may be suppression of delayed afterdepolarizations, which may be attributable in part to a decrease in Na+ influx.
Wang
Y X
YX
Department of Pharmacology, Fourth Military Medical University, Shaanxi, People's Republic of China.
Yao
X J
XJ
Tan
Y H
YH
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001599:Berberine / Q000008:administration & dosage / Q000494:pharmacology*; D002125:Calcium Gluconate / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D000860:Hypoxia; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits; D013233:Stellate Ganglion / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D009467:Neuromuscular Depolarizing Agents; D001599:Berberine; D010042:Ouabain; D002125:Calcium Gluconate