TY - JOUR T1 - The Prolonged QT Interval: Role of Pro-inflammatory Cytokines, Reactive Oxygen Species and the Ceramide and Sphingosine-1 Phosphate Pathways JF - In Vivo JO - In Vivo SP - 619 LP - 636 VL - 29 IS - 6 AU - PETER P. SORDILLO AU - DIANA C. SORDILLO AU - LAWRENCE HELSON Y1 - 2015/11/01 UR - http://iv.iiarjournals.org/content/29/6/619.abstract N2 - Patients with QT prolongation have delayed cardiac repolarization and may suffer fatal ventricular arrhythmias. To determine the role of cytokines in causing this syndrome, we reviewed reports on patients with rheumatoid arthritis, psoriasis and other inflammatory conditions. These patients frequently have prolonged QT, which correlates with increases in tumor necrosis factor alpha, and interleukin-1β and 6. Studies in experimental models have shown that these cytokines act through stimulation of reactive oxygen species. Our review of data on phospholipidosis and on QT-shortening agents suggests a key role in QT prolongation for the ceramide/sphingosine-1-phosphate rheostat. We conclude that the cause of prolonged QT in inflammatory conditions is cytokine induction of reactive oxygen species and then ceramides, and believe that QT-prolonging agents bypass initial steps of this pathway and directly affect ceramides. Since both pro-inflammatory cytokines and numerous medications cause QT prolongation and ventricular arrhythmias by this mechanism, extra caution is needed when using these agents in patients with inflammatory conditions. ER -