Laboratory of Heart Biophysics, Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil.
Excitable Membranes Laboratory, Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Eur J Pharmacol. 2019 Sep 15;859:172488. doi: 10.1016/j.ejphar.2019.172488. Epub 2019 Jun 21.
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 (I) and L-type Ca currents (I), action potential, intracellular Ca transient, Ca 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 Ca transient but reduced I. 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, Ca sparks and waves in isolated cardiomyocytes submitted to Ca overload. In conclusion, farnesol has antiarrhythmic effect mediated by reducing of I and I along with a decrease of reactive oxygen species production and normalized Ca sparks and waves.
心律失常是导致心源性猝死的最重要的病理之一。发现具有低不良反应的新的心律失常治疗方法至关重要。法尼醇存在于具有抗氧化、抗炎和心脏保护作用的精油中。本工作旨在研究法尼醇对大鼠心脏收缩和电生理特性的影响,并评估其抗心律失常作用。评估了法尼醇对左心室发展压、心电图、钾(I)和 L 型钙电流(I)、动作电位、细胞内钙瞬变、钙火花和波以及活性氧产生的影响。在体内和体外测定了法尼醇的抗心律失常活性。结果表明,50µM 法尼醇不改变左心室发展压、心率、心电图参数和细胞内钙瞬变,但降低了 I。法尼醇缩短了 90%复极化时程的动作电位。值得注意的是,法尼醇改善了心律失常评分和最严重心律失常的发生率。法尼醇减轻了在钙超载下分离的心肌细胞中活性氧、钙火花和波的产生。综上所述,法尼醇通过降低 I 和 I,同时减少活性氧的产生,使钙火花和波正常化,从而发挥抗心律失常作用。