NERVE AND REPOLARIZATION IMAGING IN SUDDEN CARDIAC DEATH

我们最近证实了异质性心肌交感神经 室性心律失常德国牧羊犬群神经支配 心源性猝死拟议中的研究将采用地质学方法， 研究这些癫痫动物的交感神经的发育， 确定神经发育改变对肾上腺素能受体的影响， 连接和复极反应。在目标1中，我们将研究产后 心肌神经支配和灌注的发展，并将结果与 出生后室性心律失常的发展。假设是 测试是，出生后的成熟交感神经支配延迟， 这个动物群体，这种延迟的成熟是一个主要的决定因素， 室性心律失常在目标2中，我们将研究 交感神经生长对室性心律失常的表达。我们将 测试交感神经生长的调节或诱导 神经支配的均匀性将降低 心律不齐在目标3中，我们将研究区域去神经对 交感神经组织学分布、肌细胞缝隙连接和α 以及β肾上腺素能受体密度和亲和力。我们将测试假设 交感神经支配的不均匀空间梯度导致 肾上腺素能受体和缝隙连接的相关梯度。目标4将 研究交感神经支配对局部心肌发育的影响 复极化有待检验的假设是， 导致基础期心肌复极的局部异常 状态和交感神经刺激期间。这是一个独特的机会 心脏交感神经支配的发育及功能比较 交感神经对心肌灌注、信号的异常 转导、细胞间通讯和心律失常。这些研究 可以更全面地了解 交感神经系统和神经发生。

We recently demonstrated heterogeneous myocardial sympathetic innervation in a colony of German shepherd dogs with ventricular arrhythmia and sudden cardiac death. The proposed research will apply scintigraphic methods to study the development of sympathetic nerves in these arrhythmic animals, and determine the effects of altered nerve development on adrenergic receptors, gap junctions, and repolarization responses. In Aim 1, we will study the postnatal development of myocardial innervation and perfusion and compare the results to the postnatal development of ventricular arrhythmias. The hypothesis to be tested is that postnatal maturation of sympathetic innervation is delayed in this colony of animals, and this delayed maturation is a primary determinant of ventricular arrhythmia. In Aim 2, we will study the effects of modulation of sympathetic nerve growth on the expression of ventricular arrhythmias. We will test the hypothesis that modulation of sympathetic nerve growth, or induced homogeneity of innervation will decrease the frequency and severity of arrhythmias. In Aim 3, we will study effects of regional denervation on the distribution of sympathetic nerve histology, myocyte gap junctions, and alpha and beta adrenergic receptor density and affinity. We will test the hypothsosis that heterogeneous spatial gradients of sympathic innervation result in associated gradients in adrenergic receptors and gap junctions. Aim 4 will study the developmental effects of sympathetic innervation on local myocardial repolarization. The hypothesis to be tested is that heterogeneous innervation results in local abnormalities of myocardial repolarization during the basal state and during sympathetic stimulation. The unique opportunity to investigate the development of cardiac sympathetic innervation and compare functional abnormalities of the sympathetic nerves to myocardial perfusion, signal transduction, intercellular communication and cardiacarrhythmia. These studies may provide a more comprehensive understanding of the interaction of the sympathetic nervous system and arrhythmogenesis.