CORONARY VASCULAR RESPONSE TO ISCHEMIA

这一建议代表了对功能的研究的继续 冠状动脉血管系统的特征，可能 影响潜在缺血心肌的血流灌注。研究 将检查冠状动脉阻力的血管运动特征 血管，无论是在动脉畅通的流入期间还是在 关于限流性狭窄，以及侧支循环 供血冠状动脉闭塞的远端心肌。研究 将在慢性仪器化的狗身上进行表演， 冠状动脉血流量是用电磁仪测量的。 流量计和局部收缩缩短率的评估 超声波微晶。将测量心肌灌注量 使用微球，而冠状动脉窦导管将允许 心肌氧摄取率和乳酸的测定 新陈代谢。侧支血管发育将由(1)引起 将中空的塞子塞进冠状动脉，(2)通过使用 (3)反复短暂冠脉狭窄模型 闭塞。将研究以下主题：(1)做 内源性腺苷参与冠状动脉病变 冠脉循环正常时运动中的血管扩张 当近端狭窄阻碍动脉流入时？(2)有吗？ 阻力血管的持续残余血管扩张剂容量 当在存在冠状动脉狭窄的情况下进行运动时 心肌缺血？药物对血管的扩张作用 运动中的冠脉阻力血管 冠状动脉狭窄导致收缩功能改善？可以进一步 阻力血管的血管扩张会导致不良影响， 包括血流从心内膜下移开或 狭窄严重程度的被动增加，这是由于 冠状动脉扩张压？(3)冷暴露会导致 与代谢性血管扩张相反的冠脉收缩 在正常灌流的心肌中或在 是否存在冠脉狭窄？(4)冠脉侧支 能够主动收缩血管的血管，这可能会损害血液 对肾上腺素能的反应流向依赖心肌 刺激物或血管活性多肽？(5)是显著的可变性 侧支血管发育对冠状动脉的影响 闭塞与固有侧支程度的差异有关 动物之间的血管？(6)慢性冠状动脉 闭塞导致血流灌注边界的宽度增加 在相邻的正常灌流和侧支依赖之间 心肌区？

This proposal represents a continuation of studies of functional characteristics of the coronary vascular system which may influence perfusion of potentially ischemic myocardium. Studies will examine vasomotor characteristics of the coronary resistance vessels, both during unimpeded arterial inflow and in the presence of a flow-limiting stenosis, and of the collateral channels which supply myocardium distal to an occluded coronary artery. Studies will be performed in chronically instrumented dogs in which coronary artery flow is measured with an electromagnetic flowmeter and regional systolic shortening is assessed with ultrasonic microcrystals. Myocardial perfusion will be measured with microspheres while a coronary sinus catheter will allow measurement of myocardial oxygen extraction and lactate metabolism. Collateral vessel development will be induced by (1) embolizing a hollow plug into a coronary artery, (2) by use of the ameroid constrictor model, or (3) by repeated brief coronary occlusions. The following topics will be studied: (1) Does endogenously produced adenosine contribute to coronary vasodilation during exercise in the normal coronary circulation and when a proximal stenosis impedes arterial inflow? (2) Is there persistent residual vasodilator capacity of the resistance vessels when exercise in the presence of a coronary stenosis causes myocardial ischemia? Does pharmacologic vasodilation of the coronary resistance vessels during exercise in the presence of a coronary stenosis cause improved systolic function? Can further vasodilation of the resistance vessels cause undesirable effects, including a shift of blood flow away from the subendocardium or a passive increase in stenosis severity as the result of a decrease in coronary artery distending pressure? (3) Does cold exposure cause coronary vasoconstriction which opposes metabolic vasodilation produced by exercise in normally perfused myocardium or in the presence of a coronary stenosis? (4) Are the coronary collateral vessels capable of active vasoconstriction which may impair blood flow to the dependent myocardium in response to adrenergic stimuli or vasoactive peptides? (5) Is the marked variability of collateral vessel development in response to coronary artery occlusion related to differences in the degree of native collateral vascularity between animals? (6) Does chronic coronary artery occlusion cause an increase in the width of the perfusion boundary between adjacent normally perfused and collateral-dependent myocardial areas?