title: How does β-adrenergic signalling affect the transitions from ventricular tachycardia to ventricular fibrillation?
abstract: OBJECTIVE
  Ventricular tachycardia (VT) and fibrillation (VF) are the most lethal cardiac arrhythmias. The degeneration of VT into VF is associated with the breakup of a spiral wave of the action potential in cardiac tissue. β-Adrenergic (βAR) signalling potentiates the L-type Ca current (ICaL) faster than the slow delayed rectifier potassium current (IKs), which transiently prolongs the action potential duration (APD) and promotes early after depolarizations. In this study, we aimed at investigating how βAR signalling affects the transition from VT to VF.
  
  
  RESULTS
  We used a physiologically detailed computer model of the rabbit ventricular myocyte in a two-dimensional tissue to determine how spiral waves respond to βAR activation following administration of isoproterenol. A simplified mathematical model was also used to investigate the underlying dynamics. We found that the spatiotemporal behaviour of spiral waves strongly depends on the kinetics of βAR activation. When βAR activation is rapid, a stable spiral wave turns into small fragments and its electrocardiogram reveals the transition from VT to VF. This is due to the transiently steepened APD restitution induced by the faster activation of ICaL vs. IKs upon sudden βAR activation. The spiral wave may also disappear if its transient wavelength is too large to be supported by the tissue size upon sudden strong βAR activation that prolongs APD transiently. When βAR activation is gradual, a stable spiral wave remains such, because of more limited increase in both APD and slope of APD restitution due to more contemporaneous ICaL and IKs activation.
  
  
  CONCLUSIONS
  Changes in APD restitution during βAR activation revealed a novel transient spiral wave dynamics; this spatiotemporal characteristic strongly depends on the protocol of isoproterenol application.
authors.affiliation: Department of Pharmacology, University of California Davis, 451 Health Sciences Drive, GBSF Room 3502, Davis, CA 95616-8636, USA.
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Xie
authors.forename: Eleonora
authors.initials: E
authors.lastname: Grandi
authors.forename: Donald M
authors.initials: DM
authors.lastname: Bers
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sato
mesh_terms: D000200:Action Potentials; D000818:Animals; D003198:Computer Simulation; D018450:Disease Progression; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D008955:Models, Cardiovascular; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction; D017180:Tachycardia, Ventricular / Q000150:complications / Q000503:physiopathology*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology*
chemical_list: D011943:Receptors, Adrenergic, beta
keywords: Action potential duration restitution; Spiral wave; Ventricular fibrillation; Ventricular tachycardia; β-Adrenergic stimulation