title: Effects of premature anodal stimulations on cardiac transmembrane potential and intracellular calcium distributions computed by anisotropic Bidomain models.
abstract: OBJECTIVE
  Cardiac unipolar electrode stimulations induce a particular structure of the transmembrane potential distribution (Vm), called virtual electrode polarization (VEP), which plays an important role in the mechanisms of cardiac excitation, reentry induction, and ventricular defibrillation. Recent experimental studies, based on the optical mapping techniques, have shown that premature stimulations also induce significant changes in the intracellular calcium (Cai) spatial distribution. The aim of this work is to investigate and compare by means of numerical simulations the morphology of the Vm and Cai patterns, generated by applying an S1-S2 stimulation protocol with a premature S2 anodal pulse.
  
  
  RESULTS
  We perform parallel finite element simulations of a three-dimensional orthotropic Bidomain model on a block of ventricular tissue by using four membrane models of two species (guinea pig and rabbit), that incorporate the phenomenological or more detailed mechanistic descriptions of the calcium dynamics. During the S2 anodal stimulus, the Cai spatial distribution, computed with all the considered models, presents a configuration similar to the typical VEP pattern of Vm, with a minimum inside the virtual anode and two maxima in the virtual cathodes. After the S2 stimulus turns off, the anode break excitation mechanism yields a Vm pattern exhibiting a clearly propagating wavefront. Differently, the Cai patterns do not show a clear separation between the resting and the activated regions, with the exception of one of the phenomenological models considered, but they show warped dog-bone shaped equi-level lines around an elevation in the virtual anode region.
  
  
  CONCLUSIONS
  The VEP pattern of the Cai spatial distribution during the S2 stimulus is in agreement with the previous experimental studies. Moreover, the Cai minimum in the virtual anode can be mainly attributable to the outflow of calcium ions produced by the sodium-calcium (NCX) exchanger, without a significant contribution of the ICaL current.
authors.affiliation: Dipartimento di Matematica, Università degli Studi di Pavia, Via Ferrata 1, 27100 Pavia, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Colli Franzone
authors.forename: Luca F
authors.initials: LF
authors.lastname: Pavarino
authors.forename: Simone
authors.initials: S
authors.lastname: Scacchi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003198:Computer Simulation; D004554:Electric Countershock; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D008955:Models, Cardiovascular; D011817:Rabbits; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D019831:Sodium-Calcium Exchanger; D002118:Calcium
keywords: Anode break excitation; Bidomain model; Virtual electrode polarization