Anisotropic conduction block and reentry in neonatal rat ventricular myocyte monolayers

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 CVL 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 CVL, 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.

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Faculty Opinions recommendation of Anisotropic conduction block and reentry in neonatal rat ventricular myocyte monolayers.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.8237965.8661066 ◽

2011 ◽

Author(s):

Jan Kucera

Keyword(s):

Conduction Block ◽

Neonatal Rat ◽

Ventricular Myocyte ◽

Rat Ventricular Myocyte ◽

Anisotropic Conduction

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Conduction block in Purkinje fibers by homogeneous versus localized decrease of the gap junction conductance

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y98-070 ◽

1998 ◽

Vol 76 (6) ◽

pp. 630-641

Author(s):

Pascal Daleau ◽

Jean Délèze

Keyword(s):

Action Potential ◽

Gap Junction ◽

Sodium Current ◽

Resistivity Measurement ◽

Conduction Block ◽

Central Compartment ◽

Internal Resistance ◽

The Core ◽

Junction Conductance ◽

Core Conductor

Gap junction channels provide the pathway for the cell-to-cell propagation of cardiac action potential.Impairment of junctional conductance decreases conduction velocity and can cause block, two conditions that favorventricular arrhythmias and fibrillation by re-entrant excitation. These experiments were designed to examine theeffects of homogeneous versus localized decrease of the gap junction conductance on propagation of action potential inPurkinje fibers from sheep hearts. The fibers were mounted in a three-compartment chamber, and cell-to-cellconductance was progressively reduced by applying heptanol either over a central 2-mm segment or over the wholefiber length. The internal resistivities (Ri ) at which conduction of the action potential became blocked were determinedin both cases. With 3.5 mM heptanol in the central compartment, conduction failed when Ri was increased by only34.6 times the control values. In contrast, when the same concentration of heptanol was added simultaneously to allthree compartments, Ri had to rise by a factor of 7.59.4 before conduction became decremental and was blocked. Inboth situations, dV/dtmax at the time of conduction block was similarly decreased to about 50% of the control values.Other parameters being equal, a moderate decrease of the gap junction conductance and of the fast sodium current,insufficient to block propagation of the action potential when they are homogeneously distributed, become sufficient tointerrupt conduction if the action potential merges abruptly into a portion of fiber with normal internal conductivity atthe outlet of the area of increased resistance. This greater sensitivity to block is accounted for by the increase inelectrical load at the discontinuity in the core conductor between the region of increased internal resistance and thenormal part of fiber that follows. Areas of steep transition from high to low input resistances of the core conductor,such as may develop in localized ischemia, therefore appear particularly susceptible to conduction failure.Key words: electrical uncoupling, internal resistivity measurement, discontinuous internal resistance, arrhythmia, sheep heart.

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