Novotný T, Kadlecová J, Papousek I, Chroust K, Bittnerová A, Floriánová A, Cesková E, Weislamplová M, Pálenský V, Sisáková M, Toman O, Gaillyová R, Spinar J
Interní kardiologická klinika Lékarské fakulty MU a FN Brno.
Vnitr Lek. 2006 Feb;52(2):116-8.
In a long list of non-cardiovascular drugs a risk of QT interval prolongation and thus an increased risk of malignant arrhythmias has been described. The precise mechanism remains unclear. Many of these drugs are potent blockers of cardiac ion channels. Thus, prolongation of repolarization could be caused by latent ion channel genes mutations which are revealed under stress conditions.
Patients were recruited in screening of antipsychotic drugs with proarrhythmic potential, another sporadic cases were reffered from regional hospitals. In 13 individuals pathologic values of corrected QT interval (> 0.44 s in males, > 0.46 s in females) were observed. Eleven patients gave their consent to mutational analysis of KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 and KCNJ2 genes (associated with congenital long QT syndrome).
At present complete results of mutational analysis are available in 8 patients. In 5 individuals changes in DNA sequence were found which are considered normal variants according to the literature (nucleotide and aminoacid polymorphisms, intronic variants). In 1 male a KCNQ1 gene mutation A590T was identified (yet not reported in literature).
Mechanisms of drug-induced QT interval prolongation is complex and it cannot be explained simply by ion channel disorders.
在众多非心血管药物中，已发现存在QT间期延长的风险，进而导致恶性心律失常风险增加。确切机制尚不清楚。这些药物中有许多是心脏离子通道的强效阻滞剂。因此，复极化延长可能是由应激条件下显现的潜在离子通道基因突变引起的。
在筛选具有促心律失常潜力的抗精神病药物时招募患者，其他散发病例则来自地区医院。在13名个体中观察到校正QT间期的病理值（男性>0.44秒，女性>0.46秒）。11名患者同意对KCNQ1、KCNH2、SCN5A、KCNE1、KCNE2和KCNJ2基因（与先天性长QT综合征相关）进行突变分析。
目前有8名患者的突变分析完整结果。在5名个体中发现了DNA序列变化，根据文献这些变化被认为是正常变异（核苷酸和氨基酸多态性、内含子变异）。在1名男性中鉴定出KCNQ1基因突变A590T（尚未见文献报道）。
药物诱导的QT间期延长机制复杂，不能简单地用离子通道紊乱来解释。
