EFFECTS OF DRUGS UPON MYOCARDIAL HYPOXIA

本提案的长期目标是继续分析 药物对局部心肌血流量和心肌功能的影响 在不同的缺血模型中。一个主要目标将是确定 特定药物增加冠状动脉病变的机制 侧支循环血流及其对跨壁分布的影响 犬单支或多支冠脉心内膜下和心外膜下 闭塞和/或狭窄。不成熟或发育不良的狗 侧支血管(急性闭塞)和成熟或发育良好的侧支血管 将使用侧支血管(慢性闭塞)。心肌节段 功能(声学显微镜)将在正常和部分缺血时进行监测 而中央缺血区和节段缩短的改变(%SS) 与局部血流变化(放射性微球)相关。 通过使用选择性的β和α受体激动剂和拮抗剂， 特定的心动过缓药物和迷走神经刺激的重要性 被认为影响侧支循环灌注的变量的数量， 即心率、非缺血心肌小动脉阻力、α1 和α2肾上腺素能受体，将被研究。在多个 阻断研究，β受体阻滞剂的有效性， 迷走神经刺激和特定的心动过缓药物增加冠状动脉 部分闭塞冠脉远端的灌流压，从而 将研究增加到完全闭塞区域的侧支血流量 侧支血管发育不成熟或发育良好的犬。第二个大调 目的是确定不同慢通道钙离子的作用效果 通道阻滞剂对发育良好犬侧支功能的影响 附属品血管。此外，这些试剂的相对选择性 冠状动脉阻力血管扩张与心外膜大电导的对比 将对抵押品血管进行评估。放射性微球， 逆行压力和血流量将作为侧支功能的指标 对不同钙通道阻滞剂的剂量反应曲线将是 通过冠状动脉内或静脉输注获得的。硝酸甘油和 腺苷，已知选择性扩张侧支血管或 小动脉阻力血管将分别用于 比较一下。由于缺血性心脏病患者往往有多个 闭塞和/或狭窄，侧支循环程度差异很大 发展，这些研究应该对机制有重要的洞察力 某些药理药剂通过它来缓解心肌缺血。

The long term goal of the present proposal is to continue an analysis of drug actions on regional myocardial blood flow and cardiac muscle function in different models of ischemia. One major objective will be to determine mechanisms whereby specific pharmacological agents increase coronary collateral blood flow and influence its transmural distribution between subendocardium and subepicardium in dogs with single or multiple coronary occlusions and/or stenoses. Dogs with immature or poorly developed collateral vessels (acute occlusion) and ones with mature or well developed collateral vessels (chronic occlusion) will be used. Myocardial segment function (sonomicrometry) will be monitored in normal, partially ischemic and central ischemic areas and changes in segment shortening (% SS) will be correlated with changes in regional blood flow (radioactive microspheres). By using selective beta and alpha receptor agonists and antagonists, specific bradycardic agents and vagal stimulation, the importance of a number of variables which are thought to influence collateral perfusion, i.e., heart rate, arteriolar resistance in nonischemic myocardium, alpha1 and alpha2 adrenergic receptors, will be investigated. In the multiple occlusion studies, the effectiveness of beta receptor blocking agents, vagal stimulation and specific bradycardic drugs to increase coronary perfusion pressure distal to a partially occluded coronary vessel, thereby increasing collateral blood flow to a totally occluded area will be studied in dogs with immature or well-developed collateral vessels. A second major objective will be to determine the effect of different slow channel calcium entry blockers on collateral function in dogs with well developed collateral vessels. In addition, the relative selectivity of these agents to dilate coronary resistance vessels versus large epicardial conductance and collateral vessels will be assessed. Radioactive microspheres, retrograde pressure and flow will be used as indices of collateral function and dose-response curves to different calcium channel blockers will be obtained by intracoronary or intravenous infusion. Nitroglycerin and adenosine, agents known to selectively dilate collateral vessels or arteriolar resistance vessels, respectively, will be used for purposes of comparison. Since patients with ischemic heart disease often have multiple occlusion and/or stenoses and have widely varying degrees of collateral development, these studies should lend important insight as to mechanisms by which certain pharmacological agents relieve myocardial ischemia.