Developmental changes in myocardial sympathetic nerves during the postnatal period produce alterations in regional sympathetic innervation, transiently leading to partial noninnervation. Increases in sympathetic tone may be delivered unevenly over the partially noninnervated ventricle, which may lead to an increased risk of life threatening ventricular arrhythmia. We propose to map the distribution of myocardial sympathetic nerve endings in newborn animals, with I-125 metaiodobenzylguanidine (MIBG), and the distribution of myocardial perfusion with Tc-99m sestamibi, using quantitative autoradiography, and parametric images. We will correlate scintigraphic results with morphologic density of sympathetic nerves and myocyte gap junctions; along with high density electrophysiologic maps of myocardial repolarization. We will also examine how changes in spatial dispersion of repolarization provides the substrate for arrhythmias in the setting of heterogeneous innervation and increased sympathetic tone, using computer modelling. These studies may improve the understanding of mechanisms relating to unexplained sudden infant death syndrome (SlDS), the leading cause of death in infants less than one year old, and may allow non invasive detection of infants at risk.
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| Yoshioka, K; Gao, D W; Chin, M et al. (2000) Heterogeneous sympathetic innervation influences local myocardial repolarization in normally perfused rabbit hearts. Circulation 101:1060-6 |
