Biomedical Engineering Reference
In-Depth Information
then progressed around the barriers to active the entire sheet (Fig. 8d). Thus, the
ability of a focus region to propagate out into surrounding tissue depends not only on
the cell type of the tissue and the coupling conductances, but also the spatial
distribution of the coupling conductances of the sheet. We also did simulations of
propagation from a model SAN region into such spatially inhomogeneously coupled
sheets and demonstrated these phenomena for a spontaneously active focus [25].
7 Summary
We have worked over several decades now on determining the design principles for
successful propagation from a spontaneously active focus region to a surrounding
syncytium of quiescent but excitable myocardium. These principles are of
fundamental importance in the functioning of a normal SAN-Atrium interface as well
as understanding how an abnormal focus can activate the entire heart. These
principles can be briefly summarized as (1) central relative uncoupling to protect the
spontaneously firing cells from too much electrotonic inhibition, (2) a transitional
region in which the cell type and electrical coupling change from the central SAN
region to the peripheral atrial region, and (3) a distributed anisotropy to facilitate focal
activity. There is increasing detail from three-dimensional reconstructions of how cell
type and connexion type and density are distributed in such regions, such as the
elegant studies of Dobrynski et al. [7] Earlier work by Kodama and Boyett [16]
demonstrated heterogeneity of action potential types in central versus peripheral
regions of the SA node and more recent studies have demonstrated regional
differences in gap junction type and distribution [5]. Anatomical studies of the rabbit
SAN region show a very disorganized ''mesh'' of cells arranged around ''islands'' of
connective tissue. There is also a spatially heterogeneous mixture of typical ''central''
SAN cells and ''atrial'' cells at the peripheral region of the SAN where these cell
types can be distinguished by gap junction type as well as by several enzyme markers
[7]. This anatomical structure and heterogeneity may provide the central uncoupling,
the gradual transition, and the distributed anisotropy, which allows the SAN region to
propagate into the atrial tissue. Recent work by Benson et al. [3] demonstrating a
specific sodium channel mutation related to sick sinus syndrome in humans may also
indicate clinical significance of loading effects on human SAN atrial conduction. The
bidirectional effects at the SAN-Atrial interface or at the interface between an ectopic
focus in the atrium or the ventricle continue to be of considerable research interest
and clinical significance.
References
1.
Auricchio A, Klein H (2000) Arrhythmias in heart failure. Curr Treat Options Cardiovasc
Med 2(4):329-339
2.
Beeler GW, Reuter H (1977) Reconstruction of the action potential of ventricular
myocardial fibres. J Physiol 268:177- 210
3.
Benson DW, Wang DW, Dyment M, Knilans TK, Fish FA, Strieper MJ, Rhodes TH,
George AL Jr (2003) Congenital sick sinus syndrome caused by recessive mutations in the
cardiac sodium channel gene (SCN5A). J Clin Invest 112(7):1019-1028
