Abstract：
Local anesthetic (LA) cardiotoxicity is one of the main health problems in anesthesiology and pain management. This study reviewed the reported LA-induced cardiac toxicity types, risk factors, management, and mechanisms, with attention to the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in heart toxicity research. Important scientific databases were searched to find relevant articles. We briefly assessed the reported cardiotoxic effects of different types of LA drugs, including ester- and amide-linked LA agents. Furthermore, cardiotoxic effects and clinical manifestations, strategies for preventing and managing LA-induced cardiotoxic effects, pharmacokinetics, pharmacodynamics, and sodium channel dynamics regarding individual variability and genetic influences were discussed in this review. The applications and importance of hiPSC-CMs cellular model for evaluating the cardiotoxic effects of LA drugs were discussed in detail. This review also explored hiPSC-CMs\' potential in risk assessment, drug screening, and developing targeted therapies. The main mechanisms underlying LA-induced cardiotoxicity included perturbation in sodium channels, ROS production, and disorders in the immune system response due to the presence of LA drugs. Furthermore, drug-specific characteristics including pharmacokinetics and pharmacodynamics are important determinants after LA drug injection. In addition, individual patient factors such as age, comorbidities, and genetic variability emphasize the need for a personalized approach to mitigate risks and enhance patient safety. The strategies outlined for the prevention and management of LA cardiotoxicity underscore the importance of careful dosing, continuous monitoring, and the immediate availability of resuscitation equipment. This comprehensive review can be used to guide future investigations into better understanding LA cardiac toxicities and improving patient safety.
摘要：
局部麻醉药（LA）心脏毒性是麻醉和疼痛管理中的主要健康问题之一。本研究回顾了已报道的LA引起的心脏毒性类型，危险因素，管理,和机制，关注人类诱导多能干细胞来源的心肌细胞（hiPSC-CMs）在心脏毒性研究中的应用。搜索了重要的科学数据库以查找相关文章。我们简要评估了不同类型LA药物的心脏毒性作用。包括酯和酰胺连接的LA药物。此外，心脏毒性作用和临床表现，预防和管理LA引起的心脏毒性作用的策略，药代动力学，药效学,本综述讨论了关于个体差异和遗传影响的钠通道动力学。详细讨论了hiPSC-CM细胞模型在评估LA药物心脏毒性作用中的应用和重要性。这篇综述还探讨了hiPSC-CM在风险评估中的潜力，药物筛选,并开发有针对性的治疗方法。LA诱导的心脏毒性的主要机制包括钠通道的扰动，ROS生产，以及由于LA药物的存在而引起的免疫系统反应紊乱。此外，药物特异性特征包括药代动力学和药效学是LA药物注射后的重要决定因素.此外,个体患者因素，如年龄，合并症,和遗传变异强调需要一种个性化的方法来降低风险和提高患者的安全性。概述的预防和管理LA心脏毒性的策略强调了谨慎给药的重要性。连续监测,以及复苏设备的即时可用性。此综合评价可用于指导未来的研究，以更好地了解LA心脏毒性并提高患者安全性。
