MECHANISMS REGULATING RV O2 BALANCE IN CONSCIOUS ANIMALS

有意识动物中 RV O2 平衡的调节机制

• 批准号: 6559396
• 负责人: HARRY FRED DOWNEY
• 金额: $ 3.2万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6559396
• 关键词: adenosine triphosphate; bioenergetics; blood flow measurement; blood pressure; cardiovascular disorder prevention; coronary vessels; dogs; exercise; heart circulation; heart contraction; heart function; heart metabolism; heart pharmacology; heart ventricle; hemodynamics; muscle function; myocardial ischemia /hypoxia; myocardium; nitric oxide; oxygen consumption; potassium channel; tissue /cell culture; vasoconstriction; vasodilation

DESCRIPTION (Applicant's abstract): The first investigation of mechanisms regulating O2 supply-demand balance in the right ventricle (RV) of an intact, conscious animal model is proposed. Scant, earlier studies in isolated hearts and anesthetized models have produced limited and conflicting data resulting in poor understanding of mechanisms matching RV O2 supply to RV O2 demand. The proposed investigation is comprehensive and integrative. Using novel procedures developed in this laboratory for collecting samples of right coronary (RC) venous blood from a conscious animal, contributions of O2 extraction and blood flow reserves in meeting increased RV O2 requirements during inotropic, chronotropic, and hemodynamic stresses produced by exercise, elevated RV afterload, atrial pacing, and ventricular paired pulse stimulation will be investigated. Roles of O2, adenosine, K+ATP channels, alpha-adrenergic vasoconstriction, beta-adrenergic "feedforward" vasodilation, and nitric oxide (NO) in regulating RC blood flow will be addressed during increases in RV O2 demand and restrictions in O2 supply. Regional RV contractile function will be measured and related to associated changes in regional RC flow and RV O2 consumption, so RV O2 utilization efficiency can be evaluated. Metabolic studies will test the hypothesis that altered myocardial substrate selection improves RV O2 supply-demand balance if O2 supply is limited. The role of NO as a modulator of RV O2 demand as well as RC flow will be assessed. The RV is remarkably able to lower its O2 demand in the face of reduced O2 supply, so it is ideally suited for the proposed investigations of mechanisms responsible for this cardioprotective response to impending ischemia. Dogs will be surgically instrumented for collection of arterial and RC venous samples, so arteriovenous differences in O2, energy metabolites, and adenosine can be determined and RV uptake/release computed; for measuring regional RV segment shortening, RC arterial pressure, RC flow and flow distribution, RV pressure and dP/dt, aortic pressure, pulmonary artery flow; for RC arterial infusion of drugs; for atrial and ventricular pacing; and for elevating pulmonary artery pressure to increase RV afterload. This investigation supports long term objectives to delineate mechanisms regulating myocardial O2 supply and to define myocardial adjustments to perturbations of O2 supply-demand balance. Results will impact treatment of conditions which limit myocardial O2 supply relative to O2 demand.

描述（申请人的摘要）：机制的首次调查 调节完整的右心室（RV）中的O2供求平衡， 提出了有意识的动物模型。很少在孤立的心脏研究 麻醉的模型产生了有限且相互矛盾的数据，导致 对将RV O2供应与RV O2需求相匹配的机制的不良理解。这 拟议的调查是全面和综合的。使用新型程序 在该实验室开发用于收集右冠状动脉样品（RC） 有意识的动物的静脉血，O2提取和血液的贡献 在肌力期间，满足RV O2的需求增加的流量储备， 锻炼产生的表年度和血流动力学应力升高，RV升高 后负载，心房起搏和心室配对脉冲刺激将是 调查。 O2，腺苷，K+ATP通道的角色，α-肾上腺素能 血管收缩，β-肾上腺素能“进食”血管舒张和一氧化氮 （否）在RV O2增加期间，将解决调节RC血流的调节 O2供应的需求和限制。区域RV收缩功能将是 测量并与区域RC流和RV O2的相关变化有关 消耗，因此可以评估RV O2利用率。代谢 研究将检验改变心肌底物选择的假设 如果O2供应有限，请改善RV O2供需平衡。 no as的作用 将评估RV O2需求以及RC流量的调节器。房车是 面对O2供应减少，可以降低其O2需求，因此 非常适合对负责机制的拟议调查 对即将到来的缺血的这种心脏保护反应。狗将通过外科手术 用于收集动脉和RC静脉样品的仪器，因此 可以确定O2，能量代谢产物和腺苷的差异并可以确定RV 计算的吸收/发布；用于测量区域RV段缩短，RC 动脉压，RC流量和流动分布，RV压力和DP/DT，主动脉 压力，肺动脉流；用于药物的RC动脉输注；对于心房 和心室起搏；并提高肺动脉压力以增加 RV后负载。这项调查支持划定的长期目标 调节心肌O2供应并定义心肌调整的机制 O2供需平衡的扰动。结果将影响 相对于O2需求而限制心肌O2供应的条件。