HETEROGENEITY OF CORONARY ARTERY VASOMOTION

这些研究评估了冠状动脉血管活性， 冠心病 研究将首先解决假设， 不同冠状动脉节段的血管反应是不均匀的， 不同的血管扩张机制在每个节段中占主导地位， 表征近端电导和远端电阻的响应 冠状血管对内源性和外源性血管活性剂的敏感性。 近侧 冠状动脉血管运动将通过数字化的维度晶体测量 定量血管造影 对远端阻力血管的影响将是 使用长期植入的流量探头通过流量变化进行评估，或 多普勒血流导管（患者）。 对壁内传导的影响 动脉将被评估为峰值充血流量（患者和 狗）和最大扩张期间的跨壁血流分布（狗） 抵抗船 然后，研究将解决假设， 内皮主要介导和/或调节血管反应， 近端和壁内传导血管，并提供了一个内在的 一种流量传感机制，其响应于 血流增加;内皮功能障碍将抑制血流诱导 扩张传导动脉并限制心肌灌注 在一定的生理压力下。 内皮功能障碍将是 由（i）体内抑制剂（亚甲蓝，ETYA）和（ii） 临床相关的病理状况（缺血/再灌注，急性 高血压或动脉粥样硬化），其已经被证明改变 内皮介导的反应。 近端孤立节段 冠状动脉和生物测定制剂也将用于补充 完整的生理准备和评估异常， 内皮细胞损伤后内皮源性舒张因子（EDRF）的产生 功能障碍 最后，研究将检验硝酸盐 耐受性主要发生在近端传导，而不是远端传导 阻力血管;与其他鸟苷酸激活剂的交叉耐受 环化酶（EDRF和心房利钠肽）不发生。 这些 研究将进一步阐明冠心病的基本机制 生理条件下的血管舒缩。

These studies assess coronary vasomotor activity with and without coronary artery disease. Studies will first address the hypothesis that vasomotor responses of different coronary segments are heterogenous due to predominance of different vasodilator mechanisms in each segment by characterizing responses of proximal conductance and distal resistance coronary vessels to endogenous and exogenous vasoactive agents. Proximal coronary vasomotion will be measured by dimension crystals in digital quantitative angiography. Effects on distal resistance vessels will be assessed by flow changes using chronically implanted flow probes or Doppler flow catheters (patients). Effects on intramural conductance arteries will be assessed as changes in peak hyperemic flow (patients and dogs) and transmural flow distribution (dogs) during maximal dilation of resistance vessels. Studies will then address the hypothesis that the endothelium mediates and/or modulates vasomotor responses primarily in proximal and intramural conductance vessels and provides an intrinsic flow sensing mechanism that mediates uniform vasodilation in response to flow increases; endothelial dysfunction will inhibit flow induced dilation of the conductance arteries and limit myocardial perfusion during certain physiologic stresses. Endothelial dysfunction will be induced by (i) in vivo inhibitors (methylene blue, ETYA) and (ii) clinically relevant pathologic conditions (ischemia-/reperfusion, acute hypertension or atherosclerosis) which have been demonstrate to alter endothelial mediated responses. Isolated segments of the proximal coronary artery and bioassay preparations will also be used to compliment intact physiological preparations and to assess abnormalities in endothelium-derived relaxing factor (EDRF) production after endothelial dysfunction. Finally, studies will test the hypothesis that nitrate tolerance occurs primarily in proximal conductance rather than distal resistance vessels; cross tolerance with other activators of guanylate cyclase (EDRF and atrial natriuretic peptide) does not occur. These studies will further clarify fundamental mechanisms of coronary vasomotion during physiologic conditions.