FUNCTION AND GROWTH OF CORONARY COLLATERAL VESSELS

动脉粥样硬化性心脏病患者经常会出现 新的或扩大现有的冠状动脉侧支血管。 这些船只 供应闭塞血管远端的心肌区域， 可以保护心脏免于梗塞。 然而，他们通常 不能提供足够的血流来防止缺血， 增加心肌氧需求的时期。 目的 建议的研究是进一步开发一个模型， 冠状动脉侧支循环，并检查各种 可能增强或延缓这种发展的机制 循环和毛细血管密度。 猪提供了一个 冠状动脉侧支循环最小（5%） 梗死但侧支血管发育受限。 因此，在本发明中， 静息时侧支心肌的功能正常， 运动时明显减少。 在初步研究中， 表明侧支血流和局部功能 一个月后改善，梗死范围未增加 身体条件反射 在拟议的研究中，我们将审查 左回旋ameroid收缩猪在休息，并在 器械植入后7、11和16周进行运动。 最初，为了 进一步发展这一模式，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（即成熟度）和影响 更长时间的收缩对冠状动脉的发展 侧支血管 接下来我们将研究 侧支循环的两个强度更长 运动训练，β-肾上腺素受体阻滞剂和β- 肾上腺素能受体阻滞与运动训练。 解剖出 一些化学和机械刺激 运动可以促进侧支血管和毛细血管的生长， 在慢性心动过缓起搏期间和之后研究猪， 腺苷输注（机械刺激）和环氧合酶 抑制（减少前列腺素的产生）和慢性 PGE 2给药（化学刺激）。 我们预测 运动训练、心动过缓起搏、腺苷输注，以及 PGE 2给药将增强左心室的整体功能 运动中的心室。 相反，β-肾上腺素受体 阻断剂和环氧合酶抑制剂将限制 侧支血管，并减少观察到的改善， 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 调节侧支和毛细血管生长的机制。 这些研究可能会提出治疗策略， 与严重动脉粥样硬化性心脏病患者的管理 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.