Evidence map›Paper›PMID 27071826›Full record

ArticleCirculation. Arrhythmia and electrophysiology2016

Increased Late Sodium Current Contributes to the Electrophysiological Effects of Chronic, but Not Acute, Dofetilide Administration.

Xiaoliang S Qiu, Samuel Chauveau, Evgeny P Anyukhovsky, Tania Rahim, Ya-Ping Jiang, Erin Harleton, Steven J Feinmark, Richard Z Lin, Ruben Coronel, Michiel J Janse and 4 more

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In one paragraph

Article in Circulation. Arrhythmia and electrophysiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Inhibition of theThe Journal of pharmacology and experimental therapeutics · 2018
    Article
  6. Review
  7. AnFrontiers in pharmacology · 2018
    Article
  8. Acquired long QT syndrome and phosphoinositide 3-kinase.Trends in cardiovascular medicine · 2017
    Review
  9. A stable cell line inducibly expressing hERG1a/1b heteromeric channels.Journal of pharmacological and toxicological methods
    Article
  10. Refractory Torsades de Pointes Due to Dofetilide Overdose.Journal of investigative medicine high impact case reports
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Xiaoliang S QiuFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.).
Samuel ChauveauFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.).
Evgeny P AnyukhovskyFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.).
Tania RahimFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.).
Ya-Ping JiangFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.).
Erin HarletonFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.).
Steven J FeinmarkFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.).
Richard Z LinFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.).
Ruben CoronelFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.).
Michiel J JanseFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.).
Tobias OpthofFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.).
Tove S RosenFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.).
Ira S CohenFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.). Ira.Cohen@stonybrook.edu.
Michael R RosenFrom the Department of Physiology and Biophysics, Stony Brook University, NY (X.S.Q., S.C., E.P.A., T.R., Y.-P.J., R.Z.L., I.S.C.); Departments of Pharmacology (E.H., S.J.F., M.R.R.) and Pediatrics (T.S.R., M.R.R.), College of Physician and Surgeons of Columbia University, New York, NY; Medical Service, Northport VA Medical Center, NY (R.Z.L.); Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands (R.C., M.J.J., T.O.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Department of Medical Physiology, University Medical Center Utrecht, The Netherlands (T.O.).

Funding

Novel ion channel approaches to reentrant arrythymiasR01HL094410 · NHLBI · STATE UNIVERSITY NEW YORK STONY BROOK · PI COHEN, IRA S · 2009 to 2013
$3.8M
NHLBI NIH HHS HL-094410NHLBI NIH HHS R01 HL094410
6 · The paper itself

Abstract

backgroundDrugs are screened for delayed rectifier potassium current (IKr) blockade to predict long QT syndrome prolongation and arrhythmogenesis. However, single-cell studies have shown that chronic (hours) exposure to some IKr blockers (eg, dofetilide) prolongs repolarization additionally by increasing late sodium current (INa-L) via inhibition of phosphoinositide 3-kinase. We hypothesized that chronic dofetilide administration to intact dogs prolongs repolarization by blocking IKr and increasing INa-L. METHODS AND

resultsWe continuously infused dofetilide (6-9 μg/kg bolus+6-9 μg/kg per hour IV infusion) into anesthetized dogs for 7 hours, maintaining plasma levels within the therapeutic range. In separate experiments, myocardial biopsies were taken before and during 6-hour intravenous dofetide infusion, and the level of phospho-Akt was determined. Acute and chronic dofetilide effects on action potential duration (APD) were studied in canine left ventricular subendocardial slabs using microelectrode techniques. Dofetilide monotonically increased QTc and APD throughout 6.5-hour exposure. Dofetilide infusion during ≥210 minutes inhibited Akt phosphorylation. INa-L block with lidocaine shortened QTc and APD more at 6.5 hours than at 50 minutes (QTc) or 30 minutes (APD) dofetilide administration. In comparison, moxifloxacin, an IKr blocker with no effects on phosphoinositide 3-kinase and INa-L prolonged APD acutely but no additional prolongation occurred on chronic superfusion. Lidocaine shortened APD equally during acute and chronic moxifloxacin superfusion.

conclusionsIncreased INa-L contributes to chronic dofetilide effects in vivo. These data emphasize the need to include time and INa-L in evaluating the phosphoinositide 3-kinase inhibition-derived proarrhythmic potential of drugs and provide a mechanism for benefit from lidocaine administration in clinical acquired long QT syndrome.

Indexed as

AnimalsDisease Models, AnimalDogsDose-Response Relationship, DrugElectrophysiological PhenomenaHeart VentriclesInfusions, IntravenousLong QT SyndromeMalePatch-Clamp TechniquesPhenethylaminesPotassium Channel BlockersSodiumSulfonamidesdofetilidePhenethylaminesPotassium Channel BlockersSodiumSulfonamidesdofetilidedogslidocainelong QT syndromePI3-kinase

Identifiers

PMID27071826
PMCPMC4850912

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