Calcium overload-induced arrhythmia is suppressed by farnesol in rat heart
Calcium overload-induced arrhythmia is suppressed by farnesol in rat heart
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DOI：
10.1016/j.ejphar.2019.172488
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发表时间：
2019-09-15
影响因子：
5
通讯作者：
Lins de Vasconcelos, Carla Maria
中科院分区：
文献类型：
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作者：
de Souza, Diego Santos;Rodrigues de Menezes-Filho, Jose Evaldo;Lins de Vasconcelos, Carla Maria
心律失常是导致猝死的最重要的病理之一。发现具有低副作用的心律失常的新治疗选择是至关重要的。法尼醇存在于精油中，具有抗氧化、抗炎和心脏保护作用。本工作的目的是研究法尼醇对大鼠心脏收缩和电生理特性的影响，并评价其抗心律失常作用。观察法尼醇对大鼠左心室收缩压、心电图、钾电流（I-k）、L型钙电流（I-Ca、I-L）、动作电位、细胞内钙瞬变、钙火花和钙波以及活性氧产生的影响。在体内和离体测定法尼醇的抗肿瘤活性。结果表明，50 μ M法尼醇对左室发展压、心率、心电图参数及细胞内钙瞬变无明显影响，但可降低I-Ca、I-L。法尼醇减少90%复极化时的动作电位时程。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。法尼醇减弱了游离心肌细胞中活性氧、钙火花和钙波的产生。结果表明，法尼醇通过降低I-Ca、I-L和I-K，沿着减少活性氧的产生和正常化的Ca ~（2+）火花和波而发挥抗肿瘤作用。
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-k) and L-type Ca2+ currents (I-Ca,I- 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 mu M farnesol did not alter left ventricular developed pressure, heart rate, ECG parameters and intracellular Ca2+ transient but reduced I-Ca,I-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 I-Ca,I- L and I-K along with a decrease of reactive oxygen species production and normalized Ca2+ sparks and waves.