AUTONOMIC RECEPTOR FUNCTION IN MYOCARDIAL ISCHEMIA

心肌缺血一小时可导致β-肾上腺素能增加 受体密度和β-肾上腺素能受体的解偶联 腺苷环化酶与GTP调节蛋白的减少有关， G(S-阿尔法)。这项研究提案的目的是为了检查 这些变化的机制和时间进程，以及是否 冠状动脉再灌注后，这种变化是可逆的。一大特点 在有意识的动物中进行生理学的联合研究是有仪器的吗？ 缺血时心内膜下和心外膜下壁运动的测量 以及来自同一心脏的生化测量的非缺血区。 冠状动脉闭塞和再灌流将通过直接 冠脉血流量的测量(多普勒技术)和局部 心肌血流量(放射性微球技术)。第二 实验设计的关键特征是研究 缺血区心内膜下和心外膜下区域与 心内膜下和心外膜下的控制值 来自同一个心脏的非缺血区。具体地说，β肾上腺素能 受体激动剂和拮抗剂结合，腺苷环化酶活性，环状 AMP和GTP调节蛋白将在急性白血病模型中进行检测。 心肌缺血。在确定变化的时间进程之后 自主神经受体和偶联到腺苷环化酶，它将 确定这些变化是否可由冠状动脉逆转 再灌注。另一个主要目标是确定更改是否 跨壁或跨心肌壁的局部受累 整个心肌壁的缺血程度。这些实验将是 比较心内膜下和心内膜下缺血程度更大的地方 在心内膜下和心内膜下同样强烈。除了检查 在体心肌壁运动和细胞变化的反应性 异丙肾上腺素对β-肾上腺素能的刺激作用机制可能是 通过检查冠状动脉闭塞的影响和 存在和不存在α-和β-肾上腺素能时的再灌注 受体阻断，也在脱敏的心脏，诱导 去甲肾上腺素水平长期升高。

One hour of myocardial ischemia results in increased beta-adrenergic receptor density but uncoupling of the beta-adrenergic receptor from adenylate cyclase associated with decreases in the GTP regulatory protein, G(s-alpha). The goals of this research proposal are directed at examining the mechanism and time course of these changes as well as whether the changes are reversible with coronary artery reperfusion. One major feature is the combined study of physiology in the conscious animal instrumented for measurement of subendocardial and subepicardial wall motion in ischemic and nonischemic zones with biochemical measurements from the same hearts. Coronary artery occlusion and reperfusion will be verified by direct measurement of coronary blood flow (Doppler technique) and regional myocardial blood flow (radioactive microsphere technique). The second critical feature of the experimental design is the study of the changes in subendocardial and subepicardial regions of the ischemic zone compared with respective control values in the subendocardium and subepicardium in the non-ischemic zone from the same hearts. Specifically ,beta-adrenergic receptor agonist and antagonist binding, adenylate cyclase activity, cyclic AMP, and GTP regulatory proteins will be examined in models of acute myocardial ischemia. After determining the time course of changes in autonomic receptors and coupling to adenylate cyclase, it will be determined whether the changes are reversible by coronary artery reperfusion.Another major goal is to determine whether changes are transmural or affected regionally across the myocardial wall varying with the level of ischemia across the myocardial wall. These experiments will be compared where ischemia is more intense subendocardially and where ischemia is equally intense in subepi- and subendocardium. In addition to examining the responsiveness of in vivo myocardial wall motion and cellular changes to beta-adrenergic stimulation with isoproterenol, mechanisms will be addressed by examining the effects of coronary artery occlusion and reperfusion in the presence and absence of alpha- and beta-adrenergic receptor blockades and also in the desensitized heart, induced by chronically elevated norepinephrine levels.