CATECHOLAMINE RELEASE IN THE HEART

这个项目的长期目标是更深入地了解 控制肾上腺素能释放和随后移除的过程 心脏组织中的神经递质。这一点的重点是 将应用于物理过程(真正的扩散和散装 运输)将去甲肾上腺素(NE)从心脏间质中移除。 拟议中的实验的具体目标是确定 心率变化对神经释放去甲肾上腺素的影响 为了将这些效应与动物的神经胺摄取进行比较 与动物体内的摄取机制保持一致 抑制，并确定心率变化的机制 更改变送器的移除。我们将诱发完全性房室 麻醉的狗，这样我们就可以人工调整心脏的速度 宽广的频率范围。我们会刺激心脏的交感神经 具有恒定频率的脉冲序列。我们将衡量(A) 稳态室性变力反应和去甲肾上腺素外溢进入 紧张性交感神经刺激时的冠状静脉窦血，以及(B) 交感神经停止后立即这些反应的衰变 刺激。我们将评估扩散在NE冲刷中的作用 通过插入左冠状动脉主干从心脏间质中取出 以及改变动脉血流量。我们将评估Bulk的作用 通过保持冠状动脉血流量恒定来运输。我们会有所不同 一组实验的起搏频率和收缩幅度会有所不同 另一组人的力量。在后一组，全心肺转流术 将建立，收缩强度将通过插入 充满液体的球囊进入左室腔并改变 液体体积。对NE消散机制的了解是重要的， 因为消散率是NE浓度的决定因素。 心脏组织，因此是心脏疾病的关键决定因素 性能。

The long-term objective of this project is to gain more insight into the processes that govern the release and subsequent removal of the adrenergic neurotransmitter in cardiac tissues. The major emphasis of this application will be on the physical processes (true diffusion and bulk transport) that remove norepinephrine (NE) from the cardiac interstitium. The specific aims of the proposed experiments are to determine the influence of changes in heart rate on the removal of neurally released NE, to compare these effects in animals with the neuronal amine uptake mechanism intact with those in animals with the uptake mechanism suppressed, and to determine the mechanisms by which changes in heart rate alter the removal of transmitter. We will induce complete atrioventricular block in anesthetized dogs so that we can pace the heart artificially over a wide frequency range. We will stimulate the cardiac sympathetic nerves with trains of constant frequency pulses. We will measure (a) the steady-state ventricular inotropic responses and NE overflows into the coronary sinus blood during tonic sympathetic stimulation, and (b) the decays of those responses immediately after cessation of sympathetic stimulation. We will assess the role of diffusion in the washout of NE from the cardiac interstitium by cannulating the left main coronary artery and varying the arterial blood flow. We will assess the role of bulk transport by holding coronary arterial blood flow constant. We will vary pacing frequency in one group of experiments and will vary contractile strength in another group. In this latter group, total heart-lung bypass will be instituted, and contractile strength will be varied by inserting a fluid-filled balloon into the left ventricular cavity and altering the fluid volume. Knowledge of the mechanisms of NE dissipation are important, because the rate of dissipation is a determinant of the NE concentration in the cardiac tissues, and hence is a critical determinant of cardiac performance.