Gao YaNan, Chen Bo, Zhang Xue, Yang Rui, Hua QingLi, Li BaiDong
Anesthesiology Department, Daqing Longnan Hospital, Daqing, People's Republic of China.
ICU, Daqing Longnan Hospital, Daqing, People's Republic of China.
J Int Med Res. 2020 Aug;48(8):300060520942619. doi: 10.1177/0300060520942619.
Bupivacaine is an amide local anesthetic with possible side effects that include an irregular heart rate. However, the mechanism of bupivacaine-induced cardiotoxicity has not been fully elucidated, thus we aimed to examine this mechanism.
We performed electrocardiogram recordings to detect action potential waveforms in Sprague Dawley rats after application of bupivacaine, while calcium (Ca) currents in neonatal rat ventricular cells were examined by patch clamp recording. Western blot and quantitative real-time polymerase chain reaction assays were used to detect the expression levels of targets of interest.
In the present study, after application of bupivacaine, abnormal action potential waveforms were detected in Sprague Dawley rats by electrocardiogram recordings, while decreased Ca currents were confirmed in neonatal rat ventricular cells by patch clamp recording. These alterations may be attributed to a deficiency of Ca1.3 (L-type) Ca channels, which may be regulated by the multifunctional protein calreticulin.
The present study identifies a possible role of the calreticulin-Ca1.3 axis in bupivacaine-induced abnormal action potentials and Ca currents, which may lead to a better understanding anesthetic drug-induced cardiotoxicity.
布比卡因是一种酰胺类局部麻醉药，可能会产生包括心率不齐在内的副作用。然而，布比卡因诱发心脏毒性的机制尚未完全阐明，因此我们旨在研究这一机制。
我们对应用布比卡因后的斯普拉格-道利大鼠进行心电图记录以检测动作电位波形，同时通过膜片钳记录检测新生大鼠心室细胞中的钙（Ca）电流。采用蛋白质免疫印迹法和定量实时聚合酶链反应测定法检测相关靶点的表达水平。
在本研究中，应用布比卡因后，通过心电图记录在斯普拉格-道利大鼠中检测到异常动作电位波形，同时通过膜片钳记录证实新生大鼠心室细胞中的钙电流降低。这些改变可能归因于Ca1.3（L型）钙通道的缺乏，而这可能受多功能蛋白钙网蛋白的调节。
本研究确定了钙网蛋白-Ca1.3轴在布比卡因诱发的异常动作电位和钙电流中可能发挥的作用，这可能有助于更好地理解麻醉药物诱发的心脏毒性。
