Shen Xiaofeng, Wang Fuzhou, Xu Shiqin, Qian Yanning, Liu Yusheng, Yuan Hongmei, Zhao Qingsong, Feng Shanwu, Guo Xirong, Xu Jianguo, Yang Jie
Departmento de Anestesiologia do Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University.
Rev Bras Anestesiol. 2010 Jul-Aug;60(4):445-54. doi: 10.1016/S0034-7094(10)70055-6.
Local anesthetics are used broadly to prevent or reverse acute pain and treat symptoms of chronic pain. Local anesthetic-induced cardiotoxic reaction has been considered the accidental event without currently effective therapeutic drugs except for recently reported intralipid infusion whose possible mechanism of action is not well known.
Cardiolipin, an anionic phospholipid, plays a key role in determining mitochondrial respiratory reaction, fatty acid metabolism and cellular apoptosis. Mitochondrial energy metabolism dysfunction is suggested as associated with local anesthetic cardiotoxicity, from an in vitro study report that the local anesthetic cardiotoxicity may be due to the strong electrostatic interaction of local anesthetics and cardiolipin in the mitochondria membrane, although there is a lack for experimental evidence. Herein we hypothesized that local anesthetic-cardiolipin interactions were the major determinant of local anesthetic-associated cardiotoxic reaction, established by means of theoretic and structural biological methods. This interacting model would give an insight on the underlying mechanism of local anesthetic cardiotoxicity and provide clues for further in depth research on designing preventive drugs for such inadvertent accidence in routine clinical practice.
The interaction between local anesthetic and mitochondrial cardiolipin may be the underlying mechanism for cardiotoxicity affecting its energy metabolism and electrostatic status.
局部麻醉药广泛用于预防或缓解急性疼痛以及治疗慢性疼痛症状。局部麻醉药引起的心脏毒性反应一直被视为偶发事件，目前除了最近报道的脂肪乳输注外，尚无有效的治疗药物，其可能的作用机制也尚不明确。
心磷脂是一种阴离子磷脂，在决定线粒体呼吸反应、脂肪酸代谢和细胞凋亡方面起关键作用。体外研究报告表明线粒体能量代谢功能障碍与局部麻醉药心脏毒性有关，尽管缺乏实验证据，但局部麻醉药心脏毒性可能是由于局部麻醉药与线粒体膜上心磷脂的强静电相互作用所致。在此，我们通过理论和结构生物学方法假设局部麻醉药 - 心磷脂相互作用是局部麻醉药相关心脏毒性反应的主要决定因素。这种相互作用模型将深入了解局部麻醉药心脏毒性的潜在机制，并为进一步深入研究设计针对此类常规临床实践中意外事件的预防药物提供线索。
局部麻醉药与线粒体心磷脂之间的相互作用可能是影响其能量代谢和静电状态的心脏毒性的潜在机制。
