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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
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Disease relevance of Arrhythmia


Psychiatry related information on Arrhythmia


High impact information on Arrhythmia

  • At the tissue level, arrhythmia could be due to slowing of electrical spread after both Na(+) current decrease and cell-to-cell uncoupling as well as cell depolarization and Ca(2+) current increase [11].
  • Thus, an Irx5 repressor gradient negatively regulates potassium-channel-gene expression in the heart, forming an inverse I(to,f) gradient that ensures coordinated cardiac repolarization while also preventing arrhythmias [12].
  • These data suggest that reduced PDE4D activity causes defective RyR2-channel function associated with heart failure and arrhythmias [13].
  • Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias [13].
  • We show that, in mice lacking the homeodomain transcription factor Irx5, the cardiac repolarization gradient is abolished due to increased Kv4.2 potassium-channel expression in endocardial myocardium, resulting in a selective increase of the major cardiac repolarization current, I(to,f), and increased susceptibility to arrhythmias [12].

Chemical compound and disease context of Arrhythmia

  • In one case the available Fab fragment supply was inadequate to reverse a massive suicidal ingestion of digoxin, and the patient died after recurrent ventricular arrhythmias [14].
  • Titration of the dose of a calcium-entry-blocking agent (verapamil, diltiazem, or nifedipine) against the ability of ergonovine to provoke spasm was successful in preventing both the provocation of spasm and arrhythmias in all four patients who were tested [15].
  • Oral flecainide acetate for the treatment of ventricular arrhythmias [16].
  • The risk of a recurrence of arrhythmia was significantly lower in patients who received sotalol than in those who received other antiarrhythmic drugs, and the risk was lower in those who had not previously failed to respond to antiarrhythmic drugs than in those who had [17].
  • Cardiac arrhythmias associated with disopyramide [18].

Biological context of Arrhythmia


Anatomical context of Arrhythmia


Gene context of Arrhythmia

  • MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia [28].
  • SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome [29].
  • Mutations in the three known genes of the KCNQ branch of the K+ channel gene family underlie inherited cardiac arrhythmias (in some cases associated with deafness) and neonatal epilepsy [30].
  • LQT was the primary cardiac manifestation, present in 71% of KCNJ2 mutation carriers, with ventricular arrhythmias present in 64% [20].
  • With the exception of KCNE3, mutations in all these partner subunits have been found to lead to an increased propensity for cardiac arrhythmias [31].

Analytical, diagnostic and therapeutic context of Arrhythmia


  1. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. Echt, D.S., Liebson, P.R., Mitchell, L.B., Peters, R.W., Obias-Manno, D., Barker, A.H., Arensberg, D., Baker, A., Friedman, L., Greene, H.L. N. Engl. J. Med. (1991) [Pubmed]
  2. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators. Cohn, J.N., Goldstein, S.O., Greenberg, B.H., Lorell, B.H., Bourge, R.C., Jaski, B.E., Gottlieb, S.O., McGrew, F., DeMets, D.L., White, B.G. N. Engl. J. Med. (1998) [Pubmed]
  3. FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Wehrens, X.H., Lehnart, S.E., Huang, F., Vest, J.A., Reiken, S.R., Mohler, P.J., Sun, J., Guatimosim, S., Song, L.S., Rosemblit, N., D'Armiento, J.M., Napolitano, C., Memmi, M., Priori, S.G., Lederer, W.J., Marks, A.R. Cell (2003) [Pubmed]
  4. Clinical efficacy and electrophysiology during long-term therapy for recurrent ventricular tachycardia or ventricular fibrillation. Heger, J.J., Prystowsky, E.N., Jackman, W.M., Naccarelli, G.V., Warfel, K.A., Rinkenberger, R.L., Zipes, D.P. N. Engl. J. Med. (1981) [Pubmed]
  5. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Curran, M.E., Splawski, I., Timothy, K.W., Vincent, G.M., Green, E.D., Keating, M.T. Cell (1995) [Pubmed]
  6. Familial polymorphic ventricular arrhythmias: a quarter century of successful medical treatment based on serial exercise-pharmacologic testing. Fisher, J.D., Krikler, D., Hallidie-Smith, K.A. J. Am. Coll. Cardiol. (1999) [Pubmed]
  7. Sleep-induced apnea syndrome. Prevalence of cardiac arrhythmias and their reversal after tracheostomy. Tilkian, A.G., Guilleminault, C., Schroeder, J.S., Lehrman, K.L., Simmons, F.B., Dement, W.C. Am. J. Med. (1977) [Pubmed]
  8. The significance of the interictal spike discharge: a review. Hughes, J.R. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society. (1989) [Pubmed]
  9. Nosology of lysosomal glycogen storage diseases without in vitro acid maltase deficiency. Delineation of a neonatal form. Verloes, A., Massin, M., Lombet, J., Grattagliano, B., Soyeur, D., Rigo, J., Koulischer, L., Van Hoof, F. Am. J. Med. Genet. (1997) [Pubmed]
  10. The effect of esmolol on ST-segment depression and arrhythmias after electroconvulsive therapy. Zvara, D.A., Brooker, R.F., McCall, W.V., Foreman, A.S., Hewitt, C., Murphy, B.A., Royster, R.L. Convulsive therapy. (1997) [Pubmed]
  11. Adenosine 5'-triphosphate: a P2-purinergic agonist in the myocardium. Vassort, G. Physiol. Rev. (2001) [Pubmed]
  12. The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient. Costantini, D.L., Arruda, E.P., Agarwal, P., Kim, K.H., Zhu, Y., Zhu, W., Lebel, M., Cheng, C.W., Park, C.Y., Pierce, S.A., Guerchicoff, A., Pollevick, G.D., Chan, T.Y., Kabir, M.G., Cheng, S.H., Husain, M., Antzelevitch, C., Srivastava, D., Gross, G.J., Hui, C.C., Backx, P.H., Bruneau, B.G. Cell (2005) [Pubmed]
  13. Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias. Lehnart, S.E., Wehrens, X.H., Reiken, S., Warrier, S., Belevych, A.E., Harvey, R.D., Richter, W., Jin, S.L., Conti, M., Marks, A.R. Cell (2005) [Pubmed]
  14. Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: experience in 26 cases. Smith, T.W., Butler, V.P., Haber, E., Fozzard, H., Marcus, F.I., Bremner, W.F., Schulman, I.C., Phillips, A. N. Engl. J. Med. (1982) [Pubmed]
  15. Life-threatening ventricular arrhythmias in patients with silent myocardial ischemia due to coronary-artery spasm. Myerburg, R.J., Kessler, K.M., Mallon, S.M., Cox, M.M., deMarchena, E., Interian, A., Castellanos, A. N. Engl. J. Med. (1992) [Pubmed]
  16. Oral flecainide acetate for the treatment of ventricular arrhythmias. Anderson, J.L., Stewart, J.R., Perry, B.A., Van Hamersveld, D.D., Johnson, T.A., Conard, G.J., Chang, S.F., Kvam, D.C., Pitt, B. N. Engl. J. Med. (1981) [Pubmed]
  17. A comparison of electrophysiologic testing with Holter monitoring to predict antiarrhythmic-drug efficacy for ventricular tachyarrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring Investigators. Mason, J.W. N. Engl. J. Med. (1993) [Pubmed]
  18. Cardiac arrhythmias associated with disopyramide. Kinney, E.L., Field, E.H., Salmon, M.P., Zelis, R. N. Engl. J. Med. (1980) [Pubmed]
  19. Effect of theophylline on sleep-disordered breathing in heart failure. Javaheri, S., Parker, T.J., Wexler, L., Liming, J.D., Lindower, P., Roselle, G.A. N. Engl. J. Med. (1996) [Pubmed]
  20. Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). Tristani-Firouzi, M., Jensen, J.L., Donaldson, M.R., Sansone, V., Meola, G., Hahn, A., Bendahhou, S., Kwiecinski, H., Fidzianska, A., Plaster, N., Fu, Y.H., Ptacek, L.J., Tawil, R. J. Clin. Invest. (2002) [Pubmed]
  21. TRPC1 forms the stretch-activated cation channel in vertebrate cells. Maroto, R., Raso, A., Wood, T.G., Kurosky, A., Martinac, B., Hamill, O.P. Nat. Cell Biol. (2005) [Pubmed]
  22. A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation. Viswanathan, P.C., Benson, D.W., Balser, J.R. J. Clin. Invest. (2003) [Pubmed]
  23. Normal and abnormal consequences of apoptosis in the human heart. James, T.N. Annu. Rev. Physiol. (1998) [Pubmed]
  24. Tyrosine administration decreases vulnerability to ventricular fibrillation in the normal canine heart. Scott, N.A., DeSilva, R.A., Lown, B., Wurtman, R.J. Science (1981) [Pubmed]
  25. Contraindicated use of cisapride: impact of food and drug administration regulatory action. Smalley, W., Shatin, D., Wysowski, D.K., Gurwitz, J., Andrade, S.E., Goodman, M., Chan, K.A., Platt, R., Schech, S.D., Ray, W.A. JAMA (2000) [Pubmed]
  26. Ventricular arrhythmias in chronic stable angina pectoris with surgical or medical treatment. de Soyza, N., Murphy, M.L., Bissett, J.K., Kane, J.J., Doherty, J.E. Ann. Intern. Med. (1978) [Pubmed]
  27. Dromotropic effects of adenosine and adenosine antagonists in the treatment of cardiac arrhythmias involving the atrioventricular node. Berne, R.M., DiMarco, J.P., Belardinelli, L. Circulation (1984) [Pubmed]
  28. MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Abbott, G.W., Sesti, F., Splawski, I., Buck, M.E., Lehmann, M.H., Timothy, K.W., Keating, M.T., Goldstein, S.A. Cell (1999) [Pubmed]
  29. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Wang, Q., Shen, J., Splawski, I., Atkinson, D., Li, Z., Robinson, J.L., Moss, A.J., Towbin, J.A., Keating, M.T. Cell (1995) [Pubmed]
  30. KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Kubisch, C., Schroeder, B.C., Friedrich, T., Lütjohann, B., El-Amraoui, A., Marlin, S., Petit, C., Jentsch, T.J. Cell (1999) [Pubmed]
  31. KCNE2 confers background current characteristics to the cardiac KCNQ1 potassium channel. Tinel, N., Diochot, S., Borsotto, M., Lazdunski, M., Barhanin, J. EMBO J. (2000) [Pubmed]
  32. A comparison of electrophysiologically guided antiarrhythmic drug therapy with beta-blocker therapy in patients with symptomatic, sustained ventricular tachyarrhythmias. Steinbeck, G., Andresen, D., Bach, P., Haberl, R., Oeff, M., Hoffmann, E., von Leitner, E.R. N. Engl. J. Med. (1992) [Pubmed]
  33. Preoperative propranolol therapy and aortocoronary bypass operation. Slogoff, S., Keats, A.S., Ott, E. JAMA (1978) [Pubmed]
  34. Should survivors of myocardial infarction with low ejection fraction be routinely referred to arrhythmia specialists? Stevenson, W.G., Ridker, P.M. JAMA (1996) [Pubmed]
  35. Suppression of ventricular arrhythmias during ischemia-reperfusion by agents inhibiting Ins(1,4,5)P3 release. Du, X.J., Anderson, K.E., Jacobsen, A., Woodcock, E.A., Dart, A.M. Circulation (1995) [Pubmed]
  36. Abnormal signal-averaged electrocardiograms in patients with nonischemic congestive cardiomyopathy: relationship to sustained ventricular tachyarrhythmias. Poll, D.S., Marchlinski, F.E., Falcone, R.A., Josephson, M.E., Simson, M.B. Circulation (1985) [Pubmed]
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