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Circulation: Arrhythmia and Electrophysiology
Azithromycin is a commonly used antibiotic and is known to increase the risk of cardiovascular and sudden cardiac death; however, the underlying mechanisms are unclear. This study finds that the antibiotic acutely causes diffuse depression and prolongation of the cardiac conduction system and ion channel block. Azithromycin potentiates cardiac sodium current over the long term to promote intracellular sodium loading. These results provide a mechanistic basis for the novel form of proarrhythmia and increased risk of sudden cardiac death seen with azithromycin.
Azithromycin Causes a Novel Proarrhythmic Syndrome
Zhenjiang Yang, MD, PhD, Joseph K. Prinsen, DO, PhD, Kevin R. Bersell, PhD, Wangzhen Shen, MD, Liudmila Yermalitskaya, PhD, Tatiana Sidorova, PhD, Paula B. Luis, PhD, Lynn Hall, BA, Wei Zhang, MS, Liping Du, PhD, Ginger Milne, PhD, Patrick Tucker, PhD, Alfred L. George Jr, MD, Courtney M. Campbell, MD, PhD, Robert A. Pickett, MD, Christian M. Shaffer, BS, Nagesh Chopra, MD, Tao Yang, MD, PhD, Bjorn C. Knollmann, MD, PhD, Dan M. Roden, MD, Katherine T. Murray, MD
Correspondence to: Katherine T. Murray, MD, Division of Clinical Pharmacology, Room 559 Preston Research Bldg, Vanderbilt University School of Medicine, 2220 Pierce Ave, Nashville, TN 37232. E-mail firstname.lastname@example.org
BACKGROUND: The widely used macrolide antibiotic azithromycin increases risk of cardiovascular and sudden cardiac death, although the underlying mechanisms are unclear. Case reports, including the one we document here, demonstrate that azithromycin can cause rapid, polymorphic ventricular tachycardia in the absence of QT prolongation, indicating a novel proarrhythmic syndrome. We investigated the electrophysiological effects of azithromycin in vivo and in vitro using mice, cardiomyocytes, and human ion channels heterologously expressed in human embryonic kidney (HEK 293) and Chinese hamster ovary (CHO) cells.
METHODS AND RESULTS: In conscious telemetered mice, acute intraperitoneal and oral administration of azithromycin caused effects consistent with multi-ion channel block, with significant sinus slowing and increased PR, QRS, …