SUBENDOCARDIAL O2 SUPPLY AND DEMAND IN AORTIC STENOSIS

更深的脑组织对缺血性损伤的敏感性增加， 肥大心脏的内膜下层 对接受瓣膜置换术的患者的外科医生提出挑战 治疗主动脉瓣狭窄 我们希望研究这一机制 在主动脉瓣狭窄的慢性狗模型中增加的可接受性。 间接证据表明，肥大会影响O2平衡， 心内膜下比心外膜下更不利。 动脉内膜下的局部血流限制已经被 记录了许多疾病过程，包括心脏病 肥大，但区域02提取和02 消费是未知的。 这项建议的具体目标是 确定区域O2供应/消耗平衡， 心肌“效率”的肥厚心脏受到 不同形式的工作量急剧增加， 导致联合国系统脆弱性增加的因素 内分泌下的 所有研究将在麻醉后进行 开胸犬主动脉瓣狭窄术后6个月 像小狗一样 我们将确定区域02供应/消耗 通过结合血红蛋白02的直接测量 小动脉和静脉的饱和度， 局部血流显微分光光度法 使用放射性微球。 我们将执行这些 犬心内膜下和心外膜下测量 而且没有肥大 结合区域“工作”（ 压力-区域尺寸环）与区域O2消耗 我们将首次能够评估局部心肌 “效率”。 我们计划测试局部血流储备极限 通过最大药理学血管舒张， 使用部分冠状动脉闭塞和正常容量 血液稀释和通过对狗施加压力限制O2消耗 快速起搏，后负荷和工作负荷急剧增加 使用各种正性肌力药物，通过不同的 机制等 通过增加最大药理学血管舒张 对于这些急性压力，我们将区分02供应 和O2消耗的内在代谢限制。 为 第一次，我们将能够完全解剖出生理或 对区域氧气供应不平衡的病理生理反应 消耗和局部“效率” 从而更好地了解增加的原因 血管内膜下对缺血性损伤的脆弱性。 长- 从长远来看，我们希望研究如何改善地区02 供应/消费和使用β阻断的低效率。

The increased susceptibility to ischemic injury of the deeper, subendocardial layers of hypertrophied hearts continues to challenge the surgeon in patients undergoing valve replacement for aortic stenosis. We wish to study the mechanism of this increased susceptibilty in a chronic dog model of aortic stenosis. Indirect evidence suggests that hypertrophy affects 02 balance in the subendocardium more adversely than in the subepicardium. Regional blood flow limitations in the subendocardium have been documented for many disease processes, including cardiac hypertrophy, but the limits of regional 02 extraction and 02 consumption are unknown. The specific aims of this proposal are to determine regional 02 supply/consumption balance and myocardial "efficiency" of hypertrophied hearts subjected to different forms of acute increases in workload to dissect out the factors leading to the increased vulnerability of the subendocardium. All studies will be conducted on anesthetized open chest dogs 6 months after creation of aortic valve stenosis as puppies. We will determine regional 02 supply/consumption relationships by combining direct measurements of hemoglobin 02 saturation in small arteries and veins using microspectrophotometry with regional blood flow measurements using radioactive microspheres. We will perform these measurements in subendo- and subepicardium of dog hearts with and without hypertrophy. Combining regional "work" (area of pressure-regional dimension loops) with regional 02 consumption we will be able for the first time to assess local myocardial "efficiency". We plan to test reserve limits of regional blood flow by maximal pharmacological vasodilatation, of 02 extraction by using partial coronary artery occlusion and by normovolumic hemodilution and limits of 02 consumption by stressing the dogs with rapid pacing, with acute increases in afterload and workload using various inotropic drugs acting through different mechanisms. By adding maximal pharmacological vasodilatation to these acute stresses, we will differentiate between 02 supply and intrinsic metabolic limitations of 02 consumption. For the first time, we will be able to fully dissect out the physiological or pathophysiological responses to imbalances in regional 02 supply and consumption and local "efficiency" in cardiac hypertrophy leading to a better understanding of the cause for the increased vulnerability of the subendocardium to ischemic injury. Long- term, we wish to study ways to improve imbalances in regional 02 supply/consumption and inefficiencies using beta blockade.