Nagasaki U Link
Nagasaki University Graduate School of Biomedical Sciences 長崎大学学院医歯薬学総合研究科
 

Role of calmodulin-dependent kinase – Ca2+ in serious ventricular arrhythmia

 Description

Ventricular tachycardia and fibrillation are the leading causes of sudden cardiac death. Implantable cardioverter-defibrillator (ICD) is the first line of treatment for the malignant tachyarrhythmias and there has been an exponential increase in its use for prevention of sudden cardiac death. However, the ICD does not target the pathological substrates responsible for arrhythmic events. A significant proportion of ICD recipients experience multiple ventricular tachycardia and fibrillation episodes in a syndrome called “electrical storm”. Electrical storm is an increasingly common life-threatening emergency that requires hospitalization and intensive treatment. Electrical storm adversely affects prognosis. However, the mechanism and pathophysiology of electrical storm is poorly understood because of a lack of suitable animal models. We study a recently-developed animal model of electrical storm that features repetitive ICD firing for recurrent ventricular fibrillation and characterize electrophysiological and molecular biological alternations associated with ventricular fibrillation storm, in order to explore the molecular and cellular mechanisms underlying ventricular fibrillation transition and maintenance and develop innovative therapeutic strategies.

Rabbit Model of Ventricular Fibrillation

A rabbit model of ventricular fibrillation storm
(Circulation 2011; 123:2192-2203).

CaMKII-activation and Protein

CaMKII activation and protein phosphorylation
alterations in ventricular fibrillation storm rabbits
(Circulation 2011; 123:2183-2186).

Publications

  1. Tsuji Y, Heijman J, Nattel S, Dobrev D. Electrical storm: recent pathophysiological insights and therapeutic consequences.  Basic Res Cardiol. 2013; 108:336.  (pdf) (Pubmed: 23429935)
  2. Tsuji Y.Electrical storm and calcium signaling: a review.  J Electrocardiol.2011; 44:725-729  (pdf) (Pubmed: 22018487)
  3. Tsuji Y, Hojo M, Voigt N, El-Armouche A, Inden Y, Murohara T, Dobrev D, Nattel S, Kodama I, Kamiya K. Ca2+-related signaling and protein phosphorylation abnormalities play central roles in a new experimental model of electrical storm. Circulation123: 2192-2203, 2011.  (pdf) (Pubmed: 21555709)
  4. Qi XY, Yeh YH, Chartier D, Xiao L, Tsuji Y, Brundel BJJM, Kodama I, Nattel S. The calcium/calmodulin/kinase system and arrhythmogenic afterdepolarizations in bradycardia-related acquired long QT SyndromeCirc Arrhythmia Electrophysiol2009; 2:295-304.    (pdf) (Pubmed: 19808480)

 

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