Calcium overload-induced arrhythmia is suppressed by farnesol in rat heart

• Published in: European journal of pharmacology Vol. 859; p. 172488
• Main Authors: Souza, Diego Santos de, Menezes-Filho, José Evaldo Rodrigues de, Santos-Miranda, Artur, Jesus, Itamar Couto Guedes de, Silva Neto, Júlio Alves, Guatimosim, Silvia, Cruz, Jader Santos, Vasconcelos, Carla Maria Lins de
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.09.2019
• Subjects: Action Potentials - drug effects; Animals; Anti-Arrhythmia Agents - pharmacology; Anti-Arrhythmia Agents - therapeutic use; Arrhythmia; Arrhythmias, Cardiac - drug therapy; Arrhythmias, Cardiac - metabolism; Arrhythmias, Cardiac - pathology; Arrhythmias, Cardiac - physiopathology; Ca2+ sparks; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channel Blockers - therapeutic use; Calcium Channels, L-Type - metabolism; Calcium Signaling - drug effects; Electrocardiography - drug effects; Farnesol; Farnesol - pharmacology; Farnesol - therapeutic use; Intracellular Space - drug effects; Intracellular Space - metabolism; K+ currents; L-type Ca2+ channels; Male; Myocardial Contraction - drug effects; Oxidative stress; Oxygen - metabolism; Potassium - metabolism; Rats; Rats, Wistar; Ventricular Dysfunction, Left - drug therapy; Oxidative stress; K+ currents; Arrhythmia; Ca2+ sparks; Farnesol; L-type Ca2+ channels; L-type Ca(2+) channels; Ca(2+) sparks; K(+) currents
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2019.172488

Cardiac arrhythmias are among the most important pathologies that lead to sudden death. The discovery of new therapeutic options against arrhythmias with low adverse effects is of paramount importance. Farnesol is found in essential oils with antioxidant, anti-inflammatory and cardioprotective properties. The aim of this work was to investigate the effects of farnesol on the contractile and electrophysiological properties in rat heart and evaluate its antiarrhythmic action. It was evaluated farnesol effects on the left ventricular developed pressure, ECG, potassium (Ik) and L-type Ca2+ currents (ICa,L), action potential, intracellular Ca2+ transient, Ca2+ sparks and waves and reactive oxygen species production. Antiarrhythmic activity of farnesol was determined in vivo and ex vivo. The results showed that 50 μM farnesol did not alter left ventricular developed pressure, heart rate, ECG parameters and intracellular Ca2+ transient but reduced ICa,L. Farnesol reduced action potential duration at 90% repolarization. Notably, farnesol improved arrhythmia score and the incidence of the most severe arrhythmias. Farnesol attenuated the generation of reactive oxygen species, Ca2+ sparks and waves in isolated cardiomyocytes submitted to Ca2+ overload. In conclusion, farnesol has antiarrhythmic effect mediated by reducing of ICa,L and IK along with a decrease of reactive oxygen species production and normalized Ca2+ sparks and waves.