HYPOXIC CORONARY VASOSPASM

实验将继续进行，以分离的冠状动脉。 狗，它的最终目标是理解 冠脉痉挛冠状血管痉挛，尤指由缺氧引起的 拟议的研究将集中在响应性的变化上 与冠脉再通相关的大冠状动脉 循环停顿一段时间后的心肌。少校 经检验的工作假说是，缺血发作不仅 当血液恢复流动时会危及组织细胞，但 它还可能永久地影响人的 内皮细胞产生松弛和收缩因子。如果 这将导致有利于血管收缩的失衡，例如 一种情感可能有助于解释所报告的痉挛发作 冠状动脉血管外科或化学再通术后 床。为了确定内皮细胞的状态，我们将 比较冠脉环与冠脉环的反应 无内皮细胞。测量内皮衍生的舒张性 因子(S)，我们将对心脏节段的灌流液进行生物测定 有内皮的冠状动脉；灌流液将 进行化学分析以检测一氧化氮、羊水和 花生四烯酸的代谢物。确定释放的步骤 血管内皮衍生收缩因子(S)，我们将使用分层 准备(“三明治”)。控制冠脉病变的反应 动脉将被与那些已经被 暴露于缺血(血流停止)、缺氧(灌流 低氧血)，或者两种手法结合 再灌流。有待研究的回应包括 释放内皮源性松弛因子的物质(S) 或直接导致平滑肌松弛，以及 缺氧引起的宫缩。研究将确定是否 内皮依赖反应性的急性改变 再灌流引起的是很容易逆转的，无论是否 损伤导致冠状动脉反应性的慢性改变 动脉。高血压病患者血小板和白细胞沉积范围 将测量再灌流的动脉。几种血流动力学 演习和药剂将进行测试，以确定他们的 在一定程度上减轻再灌流后果的能力 巨大的冠状动脉。这些研究将改善 对患者观察到的再灌注损伤的认识 血流在缺血一段时间后恢复，可能有助于 防止或减弱这一过程的方法。

Experiments will continue with isolated coronary arteries of the dog, with as its ultimate goal the understanding of the causes of coronary vasospasm, in particular that resulting from hypoxia. The proposed research will focus on the changes in responsiveness of the large coronary arteries associated with reperfusion of the myocardium after a period of circulatory standstill. The major working hypothesis tested is that the ischemic episode not only endangers the tissue cells when the flow of blood is resumed, but that it also affects, probably permanently, the ability of the endothelial cells to produce relaxing and contracting factors. If this were to result in an imbalance favoring vasoconstriction, such an affect may help to explain the reported episodes of spasm after surgical or chemical reperfusion of the coronary vascular bed. To determine the status of the endothelium, we will compare the responses of rings of coronary arteries with and without endothelium. To measure endothelium-derived relaxing factor(s), we will bioassay the perfusate from segments of coronary arteries with endothelium; the perfusate will be analyzed chemically to detect nitric oxide, amonia and metabolites of arachidonic acid. To determine the release of endothelium-derived contracting factor(s), we will use layered preparations ("sandwiches"). The responses of control coronary arteries will be compared to those of arteries which have been exposed to ischemia (cessation of blood flow), hypoxia (perfusion with hypoxic blood) or either maneuver combined with reperfusion. The responses to be studied include those to substances which release endothelium-derived relaxing factor(s) or cause direct relaxation of the smooth muscle, as well as contractions evoked by hypoxia. Studies will determine whether or not the acute alteration in endothelium-dependent reactivity caused by reperfusion is readily reversible, and whether or not the injury results in chronic changes in responsiveness of the coronary artery. The extent of platelet and leukocyte deposition in reperfused arteries will be measured. Several hemodynamic maneuvers and pharmacological agents will be tested for their ability to attenuate the consequences of reperfusion at the level of the large coronary arteries. The studies will improve the understanding of the reperfusion injury observed in patients when flow is reinstated after a period of ischemia, and may help to find ways to prevent or attenuate this process.