一氧化碳中毒是煤气泄漏和火灾等情形中对人造成伤害的重要原因，即使少量接触也有可能导致心律不齐。英国一项最新研究显示，动物实验显示药物“雷诺嗪”可用于减轻一氧化碳对心脏的伤害。
心绞痛药物雷诺嗪可缓解CO中毒导致的心律不齐
英国利兹大学等机构的研究人员在新一期《美国呼吸系统和重症护理医学杂志》上报告说，他们探明了一氧化碳会导致心律不齐的原因。因为心肌细胞接触一氧化碳后，其细胞膜上一个供钠离子进出的通道会开放得比正常时间更久，最终导致心肌细胞的收缩节奏变得不正常。
研究人员想到，用于治疗心绞痛的药物雷诺嗪的作用目标正是这种钠离子通道，于是开展了动物实验。结果显示，在实验鼠吸入一氧化碳之后，如果服用雷诺嗪，可以使心律不齐的风险大幅下降。
参与研究的德里克•斯蒂尔教授说，一氧化碳会导致心律不齐这个现象已经发现了很多年，但本次研究第一次揭示了深层的机制，并随之找出了一种可能的治疗方法。由于雷诺嗪是一种已在临床应用的药物，接下来开展人类临床试验就要方便得多。
一氧化碳存在于煤气中。家中炭火不完全燃烧，以及火灾中一些物品燃烧都会产生一氧化碳，汽车的尾气中也含有少量一氧化碳。它毒性较强，会大幅降低血液携带氧气的能力，吸入过多会致人死亡，少量吸入也会导致心律不齐。
曾有研究显示，消防员等经常暴露在少量一氧化碳环境中的人士，出现心律不齐等疾病的风险较高。
Carbon Monoxide Induces Cardiac Arrhythmia via Induction of the Late Na+ Current
Mark L Dallas, Zhaokang Yang, John P Boyle, Hannah E Boycott, Jason L Scragg, Carol J Milligan, Jacobo Elies, Adrian Duke, Jérôme Thireau, Cyril Reboul, Sylvain Richard, Olivier Bernus, Derek S Steele and Chris Peers
Rationale: Clinical reports describe life-threatening cardiac arrhythmias following environmental exposure to carbon monoxide (CO) or accidental CO poisoning. Numerous case studies describe disruption of repolarization and prolongation of the QT interval, yet the mechanisms underlying CO-induced arrhythmias are unknown.
Objectives: to understand the cellular basis of CO-induced arrhythmias and to indentify an effective therapeutic approach.
Methods: Patch-clamp electrophysiology and confocal Ca2+ and nitric oxide (NO) imaging in isolated ventricular myocytes was performed together with protein S-nitrosylation to investigate the effects of CO at the cellular and molecular level, whilst telemetry was employed to investigate effects of CO on electrocardiogram recordings in vivo.
Measurements and Main Results: CO increased the sustained (late) component of the inward Na+ current, resulting in prolongation of the action potential (AP) and the associated intracellular Ca2+ transient. In > 50% of myocytes these changes progressed to early after-depolarization (EAD)-like arrhythmias. CO elevated NO levels in myocytes and caused S-nitrosylation of the Na+ channel, Nav1.5. All pro-arrhythmic effects of CO were abolished by the nitric oxide synthase inhibitor L-NAME, and reversed by ranolazine, an inhibitor of the late Na+ current. Ranolazine also corrected QT variability and arrhythmias induced by CO in vivo, as monitored by telemetry.
Conclusions: Our data indicate that the pro-arrhythmic effects of CO arise from activation of NOS, leading to NO-mediated nitrosylation of NaV1.5 and so induction of the late Na+ current. We also show that the anti-anginal drug ranolazine can abolish CO-induced EADs, highlighting a novel approach to the treatment of CO-induced arrhythmias.
文献链接：Carbon Monoxide Induces Cardiac Arrhythmia via Induction of the Late Na+ Current
