ADRENERGIC LIMITATION TO CARDIAC BLOOD FLOW IN EXERCISE

研究表明，在运动狗，i.c.注射 特异性α 1受体拮抗剂哌唑嗪增加冠脉流量 和心肌收缩功能（dp/dtmax和局部节段性 缩短）。 收缩功能的增加不是由于 心肌β 1受体激活，因为效应未减弱 阿替洛尔。 有人提出，在运动过程中， 收缩限制了冠状动脉流量的增加， 心肌性能的流量限制。 长期使用 仪表，行使狗模型，这一建议将被审查， 以下：（1）研究表明，除了alpha 1-收缩， 在冠状循环中，也可能存在α 2缩血管紧张素。 研究1将检测特异性突触后α 2阻滞剂 对运动中冠脉流量和心肌功能的影响。 (2)的增加 运动时α 1阻滞后的冠状动脉血流并不是因为 β 1受体刺激伴随代谢性血管舒张。 研究 2将解决冠状动脉流量增加是由于 由血管β 2受体刺激引起的直接扩张。 为 为此，在运动期间α-阻滞的效果将是 在普萘洛尔的一般β-阻滞剂存在下检查。 (3)如果 伴随α-阻滞的收缩功能的增加是由于 心肌灌注增加，收缩性增加， 如果心肌灌注是由 直接冠状血管扩张剂。 因此，在研究3中，i.c.总局 将使用直接冠状动脉扩张剂，例如腺苷和硝酸甘油。 (4)研究4将确定特异性α-阻滞剂对 透壁心肌灌注（示踪微球），局部氧 提取（区域静脉流出物）和区域MV 02。 进一步 检查观察到的α-阻滞效应是由于 突触前活动，α-阻滞对区域 还将测定去甲肾上腺素释放。 (5)先前实验 显示出收缩功能的增加与 采用节段长度晶体的α-阻滞后的冠状动脉血流 植入心脏内膜层 研究5将更多 仔细检查高水平的心脏交感神经刺激是否可以 在没有心外膜的情况下，引起心内膜功能的血流限制 功能 在这些研究中，特定封锁对区域 在星状扫描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灌注和功能的影响， 锻炼的

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.