FUNCTION AND GROWTH OF CORONARY COLLATERAL VESSELS

动脉粥样硬化性心脏病患者常发生 新建或扩大现有的冠脉侧支血管。这些船只 供血至闭塞血管远端的心肌区 可以保护心脏免受梗塞的侵袭。然而，他们通常 不要提供足够的血流量，以防止在 心肌耗氧量增加的时间段。目的 建议的研究的目的是进一步开发一种模型 冠脉侧支循环及检查各种 可能促进或阻碍这一发展的机制 循环和毛细血管密度。猪提供了一个模型 冠脉侧支循环最少(5%) 脑梗塞，但侧支血管发育受限。因此， 静息状态下侧支心肌功能正常，但 在运动过程中显著减少。在初步研究中，我们有 说明侧支循环血流量和局部功能 一个月后病情有所改善，但梗塞范围没有增加 体能训练。在拟议的研究中，我们将研究 左侧回旋肌收缩的猪在休息时和在 术后7周、11周和16周进行练习。最初，到 进一步发展这一模型并评估其与人类的相关性 对于动脉粥样硬化，我们将确定 微球包埋；动物年龄(即成熟期)及其影响 更长时间的狭窄对冠状动脉的发展 附属品血管。接下来，我们将研究 侧支循环到两个强度更长的时间 运动训练，β-肾上腺素能受体阻滞剂和- 通过运动训练阻断肾上腺素能受体。剖析出 一些与之相关的化学和机械刺激 可以促进侧支血管和毛细血管生长的运动， 在慢性心脏缓慢起搏期间和之后，将对猪进行研究， 腺苷输注(机械刺激)与环氧合酶 抑制(减少前列腺素的产生)和慢性 前列腺素E_2给药(化学刺激)。我们预测 运动训练，心脏起搏，腺苷输注，以及 PGE2管理将增强左翼的全球功能 运动时的脑室。相反，β-肾上腺素能受体 阻断和环氧合酶抑制将限制发展 减少侧支血管的改善 运动训练。因此，这些研究将提供证据 关于运动训练和一些化学和机械的 调节侧支血管和毛细血管生长的机制。 这些研究可能会提出治疗策略，可能会有所帮助。 危重动脉粥样硬化性心脏病人的处理 疾病。

Patients with atherosclerotic heart disease frequently develop new or enlarge existing coronary collateral vessels. These vessels supply the region of myocardium distal to the occluded vessel and may protect the heart from infarction. However, they generally do not supply sufficient blood flow to prevent ischemia during periods of augmented myocardial oxygen demands. The purpose of the proposed research is to further develop a model of the coronary collateral circulation and to examine various mechanisms that may enhance or retard development of this circulation and capillary density. The pig provides a model of the coronary collateral circulation in which there is minimal (5%) infarction but limited development of collateral vessels. Thus, function of the collateralized myocardium is normal at rest but markedly reduced during exercise. In preliminary studies we have demonstrated that collateral blood flow and regional function are improved without an increased extent of infarction after a month of physical conditioning. In the proposed studies we will examine left circumflex ameroid-constricted pigs at rest, and during exercise 7, 11 and 16 weeks post-instrumentation. Initially, to further develop this model and assess its relevance to humans with atherosclerosis, we will determine the effects of microsphere entrapment; animal age (i.e. maturity) and the effect of more prolonged constriction on the development of coronary collateral vessels. We next will examine the response of the collateral circulation to two intensities of more prolonged exercise training, beta-adrenoceptor blockade and beta- adrenoceptor blockade with exercise training. To dissect out some of the chemical and mechanical stimuli associated with exercise that may promote collateral and capillary vessel growth, pigs will be studied during and after chronic bradycardiac pacing, adenosine infusion (mechanical stimulation) and cyclooxygenase inhibition (to decrease prostaglandin production) and chronic PGE2 administration (chemical stimulation). We predict that exercise training, bradycardiac pacing, adenosine infusion, and PGE2 administration will enhance global function of the left ventricle during exercise. Conversely, beta-adrenoceptor blockade and cyclooxygenase inhibition will limit the development of collateral vessels and reduce the improvement observed with exercise training. Therefore, these studies will yield evidence about exercise training and some of the chemical and mechanical mechanisms regulating growth of collateral and capillary vessels. These studies may suggest therapeutic strategies that could help with management of patient with critical atherosclerotic heart disease.