ADRENERGIC LIMITATION TO CARDIAC BLOOD FLOW IN EXERCISE

研究表明，在锻炼的狗身上，I.C.注射用的 特异性α1受体拮抗剂哌唑嗪增加双侧冠状动脉血流量 和心肌收缩功能(dp/dtmax和局部节段 缩写)。收缩功能的增加不是由于 心肌β1受体的激活，因为其作用并未减弱 阿替洛尔。有人提出，在运动过程中，一种α-肾上腺素能 狭窄限制了冠状动脉流量的增加，并导致 心肌功能的血流受限。使用一个长期的 这项建议将作为仪器化的、锻炼的狗模型进行审查 如下：(1)研究表明，除了字母1-收缩外， 冠脉循环，也可能出现α2收缩音。 研究1将检查特定突触后α2受体阻滞剂的作用 运动中冠脉流量与心肌功能的关系。(2)增加 运动中α1受体阻滞剂后的冠脉流量不是由于增加 伴随代谢性血管扩张的β1受体刺激。学习 2将解决冠状动脉流量增加的可能性，这是由于 由刺激血管的β2受体引起的直接扩张。为 为此，运动中α-受体阻滞剂的作用将是 在普萘洛尔的β-受体阻滞剂存在的情况下检查。(3)如 与α-受体阻滞剂相伴的收缩功能增加是由于 心肌灌注量增加，收缩功能增强 如果心肌灌注是由以下因素引起的，也应该注意性能 直接的冠状动脉血管扩张剂。因此，在研究3I.C.管理 将使用直接冠状动脉扩张剂，如腺苷和硝酸甘油。 (4)研究4将确定特定的阿尔法封锁对 跨壁心肌灌注(示踪剂微球)，局部氧气 提取(局部静脉流出物)和局部MV02。为了进一步 检查所观察到的阿尔法封锁的效果是否合理的可能性 α-受体阻滞剂对突触前动作的影响 去甲肾上腺素的释放也将被确定。(5)以前的实验 表现出收缩功能的增强，与 使用节段长度晶体的α-阻滞剂后的冠脉血流 植入心脏的心内膜各层。研究5将有更多内容 仔细检查高水平的心脏交感神经刺激是否可以 在无心外膜的心内膜引起血流受限 功能。在这些研究中，特定封锁对地区和地区的影响 在星形手术期间将检查心外膜和心内膜功能 神经节刺激。这些研究的结果将对 了解肾上腺素能对心肌血流灌注和功能的影响 锻炼身体。

Studies demonstrate that in the exercising dog, i.c. injection of the specific alpha1-receptor antagonist prazosin increases both coronary flow and myocardial contractile function (dp/dtmax and regional segmental shortening). The increase in contractile function was not due to activation of myocardial beta1-receptors since the effect was not blunted by atenolol. It is proposed that during exercise, an alpha-adrenergic constriction limits the increase in coronary flow and causes a flow-limitation of myocardial performance. Using a chronically instrumented, exercising dog model, this proposal will be examined as follows: (1) Studies suggest that in addition to an alpha1-constriction in the coronary circulation, an alpha2-constrictor tone may also be present. Study 1 will examine the effects of specific postsynaptic alpha2-blockade on coronary flow and myocardial function in exercise. (2) The increase in coronary flow after alpha1-blockade during exercise is not due to increased beta1-receptor stimulation with accompanying metabolic vasodilation. Study 2 will address the possibility that the increase in coronary flow is due to a direct dilation caused by stimulation of vascular beta2-receptors. For this purpose, the effects of alpha-blockade during exercise will be examined in the presence of general beta-blockade with propranolol. (3) If the increase in contractile function accompanying alpha-blockade is due to an increase in myocardial perfusion, the increase in contractile performance should also be noted if myocardial perfusion is elicited by direct coronary vasodilators. Therefore, in Study 3 i.c. administration of direct coronary dilators, e.g. adenosine and nitroglycerine, will be used. (4) Study 4 will determine the local effects of specific alpha-blockade on transmural myocardial perfusion (tracer microspheres), regional oxygen extraction (regional venous effluents), and regional MV02. To further examine the possibility that the effects of alpha-blockade observed are due to presynaptic actions, the effects of alpha-blockade on regional norepinephrine release will also be determined. (5) Previous experiments showing an increase in contractile function associated with the increase in coronary flow following alpha-blockade employed segment length crystals implanted within the endocardial layers of the heart. Study 5 will more closely examine whether high levels of cardiac sympathetic stimulation can cause a flow-limitation of function in endocardium without epicardial function. In these studies, effects of specific blockade on regional epicardial and endocardial function will be examined during stellate ganglion stimulation. Results of these studies will be important to understanding adrenergic effects on myocardial perfusion and function in exercise.