Increased sensitivity to local anesthetic drugs: bedside to bench.
Increased sensitivity to local anesthetic drugs: bedside to bench.
复制标题
对局部麻醉药物的敏感性增加：从床边到工作台。
DOI：
10.1161/circresaha.108.182055
复制
发表时间：
2008
影响因子：
20.1
通讯作者：
Fozzard,HarryA
中科院分区：
文献类型：
--
作者：
Fozzard,HarryA
这一期的《循环研究》刊登了一篇令人惊讶的报道一位中年非裔美国人患有Brugada综合征与Na通道基因中两种广泛分离的错义突变有关并且利多卡因敏感性显著增加。1在急诊室发生癫痫发作后，患者出现单形性室性心动过速发作，并以电击终止。开始静脉注射利多卡因后，患者迅速出现Brugada现象的心电图特征。虽然局部麻醉剂（LAs）具有缓慢的关闭率，通常会引起这种心电图变化，但利多卡因没有报道。在确定了该个体Na通道α亚基基因的2个突变后，Barajas-Martinez等人1将突变通道暴露于利多卡因中，发现对阻滞的敏感性明显增加。在同一个钠通道基因中发现两个不相关的突变是不寻常的。Ackerman等人报道，其中1个突变，L1308F，是一种罕见的多态性（每319人中出现一次），在非裔美国人人群中，而在白人、亚洲人或西班牙裔人群中则没有。Barajas-Martinez等人指出，他们在1%的白人人群中发现了这种多态性。以前没有关于这种多态性的利多卡因敏感性的研究报道，但现在看来，L1308F多态性的个体可能存在局部麻醉毒性的风险。这个问题值得关注。
This issue of Circulation Research contains the surprising report of a middle-aged African American with Brugada syndrome associated with 2 widely separated missense mutations in the Na channel gene and with dramatically increased lidocaine sensitivity. 1 Following a seizure in the emergency room, the patient developed an episode of monomorphic ventricular tachycardia terminated by electric shock. After IV lidocaine was started, the patient quickly developed the ECG characteristics of Brugada phenomenon. Although local anesthetics (LAs) with slow off rates typically induce such ECG changes, this has not been reported for lidocaine. After identifying the 2 mutations in the Na channel α subunit gene of this individual, Barajas-Martinez et al1 exposed the mutated channel to lidocaine and found markedly increased sensitivity to block.The finding of 2 unrelated mutations in the same Na channel gene is unusual. Ackerman et al2 reported that 1 of these mutations, L1308F, is a rare polymorphism (seen once in 319) in an African-American population but not in white, Asian, or Hispanic populations. Barajas-Martinez et al1 indicated that they have seen this polymorphism in 1% of their white population. No previous studies of lidocaine sensitivity have been reported for this polymorphism, but it now seems possible that individuals with the L1308F polymorphism are at risk of local anesthetic toxicity. This question deserves follow-up.