CATECHOLAMINE RELEASE IN THE HEART

该项目的长期目标是更深入地了解 控制肾上腺素能神经递质释放和随后清除的过程 心脏组织中的神经递质。 这其中的主要重点 应用程序将在物理过程（真正的扩散和散装 运输），其从心脏内膜去除去甲肾上腺素（NE）。 拟议实验的具体目的是确定 心率变化对神经释放NE的去除的影响， 将动物的这些效应与神经元胺摄取进行比较， 与具有摄取机制的动物中的机制相同 抑制，并确定心率变化的机制， 更改发送器的移除。 我们会诱导完全性房室传导 在麻醉的狗中进行阻滞，这样我们就可以人工起搏心脏， 频率范围很宽。 我们会刺激心脏的交感神经 用恒定频率的脉冲串。 我们将以（a） 稳态心室变力性反应和NE溢出到 紧张性交感神经刺激期间的冠状窦血液，和（B） 这些反应的衰减后立即停止交感神经 刺激. 我们将评估扩散在NE洗脱中的作用。 从左主冠状动脉插管 并改变动脉血流量。 我们将评估散装的作用 通过保持冠状动脉血流恒定来运输。 我们会有所不同 起搏频率在一组实验中， 另一组的力量。 在后一组中， 将被提起，收缩强度将通过插入 液体填充的球囊进入左心室腔， 流体体积。 NE耗散机制的知识是重要的， 因为耗散率是NE浓度的决定因素， 心脏组织，因此是心脏的关键决定因素 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.