Anisotropic conduction block and reentry in neonatal rat ventricular myocyte monolayers

Carlos De Diego, Fuhua Chen, Yuanfang Xie, Rakesh K. Pai, Leonid Slavin, John Parker, Scott T. Lamp, Zhilin Qu, James N. Weiss, Miguel Valderrábano

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Anisotropy can lead to unidirectional conduction block that initiates reentry. We analyzed the mechanisms in patterned anisotropic neonatal rat ventricular myocyte monolayers. Voltage and intracellular Ca (Cai) were optically mapped under the following conditions: extrastimulus (S1S2) testing and/or tetrodotoxin (TTX) to suppress Na current availability; heptanol to reduce gap junction conductance; and incremental rapid pacing. In anisotropic monolayers paced at 2 Hz, conduction velocity (CV) was faster longitudinally than transversely, with an anisotropy ratio [AR = CVL/CVT, where CVL and CVT are CV in the longitudinal and transverse directions, respectively], averaging 2.1 ± 0.8. Interventions decreasing Na current availability, such as S1S2 pacing and TTX, slowed CV L and CVT proportionately, without changing the AR. Conduction block preferentially occurred longitudinal to fiber direction, commonly initiating reentry. Interventions that decreased gap junction conductance, such as heptanol, decreased CVT more than CV L, increasing the AR and causing preferential transverse conduction block and reentry. Rapid pacing resembled the latter, increasing the AR and promoting transverse conduction block and reentry, which was prevented by the Cai chelator 1,2-bis oaminophenoxy ethane-N,N,N′,N′- tetraacetic acid (BAPTA). In contrast to isotropic and uniformly anisotropic monolayers, in which reentrant rotors drifted and self-terminated, bidirectional anisotropy (i.e., an abrupt change in fiber direction exceeding 45°) caused reentry to anchor near the zone of fiber direction change in 77% of monolayers. In anisotropic monolayers, unidirectional conduction block initiating reentry can occur longitudinal or transverse to fiber direction, depending on whether the experimental intervention reduces Na current availability or decreases gap junction conductance, agreeing with theoretical predictions.

Original languageEnglish (US)
Pages (from-to)H271-H278
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume300
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Anisotropy
  • Myocyte monolayers
  • Optical mapping
  • Reentry

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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