NERVE AND REPOLARIZATION IMAGING IN SUDDEN CARDIAC DEATH

我们最近证实了异质性心肌交感神经。 一群患有室性心律失常的德国牧羊犬的神经支配 心源性猝死。拟议的研究将应用闪烁照相方法来 研究这些心律失常动物的交感神经发育，以及 确定神经发育改变对肾上腺素能受体GAP的影响 交界处和复极反应。在目标1中，我们将研究出生后 心肌神经支配和心肌灌注的研究进展及其与 室性心律失常的出生后发展。假设是 试验表明，交感神经的出生后成熟延迟在 这群动物，以及这种延迟成熟是决定 室性心律失常。在目标2中，我们将研究调制的效果 交感神经生长对室性心律失常的表达。我们会 检验以下假设：交感神经生长的调节或诱导 神经支配的同质性将降低心绞痛的发生频率和严重程度 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、心肌细胞缝隙连接和α-受体的分布 以及β肾上腺素能受体密度和亲和力。我们将检验这一假设 交感神经分布的不同空间梯度导致 肾上腺素能受体和缝隙连接的相关梯度。目标4将 交感神经支配对局部心肌发育影响的研究 复极化。需要检验的假设是异质性神经支配 在基础状态下导致局部心肌复极异常 状态和交感神经刺激期间。独一无二的调查机会 心脏交感神经支配的发展及其功能比较 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 交感神经系统与心律失常发生。

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.