REGIONAL, NON-ISCHEMIC MYOCARDIAL HYPOXIA

区域性非缺血性心肌缺氧

• 批准号: 2217710
• 负责人: HARRY FRED DOWNEY
• 金额: $ 17.98万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2217710
• 关键词: adrenergic receptor; aminophylline; blood volume; coronary disorder; coronary vasodilator; dipyridamole; dogs; heart circulation; heart function; heart pharmacology; myocardial ischemia /hypoxia; nifedipine; oxygen tension; purine /pyrimidine metabolism; vascular resistance; vasoactive agent; vasomotion

An investigation of the physiological mechanisms underlying coronary and myocardial responses to non-ischemic and ischemic hypoxia is proposed. The left anterior descending coronary artery of the anesthetized dog will be perfused with blood of controlled oxygen content (non-ischemic hypoxia) or have its flow occluded (ischemic hypoxia). Blood will be deoxygenated by an extracorporeal canine lung. Coronary arterial and venous oxygen tension and content, blood flow (flowmeter and microsphere distribution), myocardial oxygen tension (polarographic technique), contractile function (ultrasonic segment-length gauge), concentrations of nucleosides and high energy phosphates (HPLC), and epicardial electrograms will be measured. Perturbations of myocardial oxygen supply/demand relationships will be performed during non-ischemic hypoxia to differentiate mechanisms due to oxygen deficient from those due to vasoactive metabolites. These mechanisms will be further clarified by determining during non-ischemic hypoxia the action of agents which alter the vasodilator response to brief ischemia and/or exogenous adenosine (adenosine deaminase, aminophylline, dipyridamole, nifedipine). Mechanisms which determine the rate of recovery of vascular tone following myocardial hypoxia will be also investigated. Further studies will determine long term (4 hr) effects of non-ischemic myocardial hypoxia on coronary hemodynamic parameters (regional flow, small vessel blood volume, collateral conductance) and on myocardial contractile function and concentrations of nucleosides and high energy phosphates. By comparing these findings with measurements after a similar period of ischemic hypoxia, the importance of hypoxia per se and metabolite build-up during long term ischemia will be defined. Recovery of coronary hemodynamic function, myocardial contractile function, and concentrations of nucleosides and high energy phosphates during reoxygenation following an extended period of non-ischemic hypoxia will be determined and compared with recovery of these parameters during reperfusion following a similar period of ischemic hypoxia. The investigation is in accordance with long term objectives 1) to define mechanisms which adjust coronary blood flow to meet myocardial oxygen requirements; and 2) to define the vulnerability of these mechanisms to ischemic and hypoxic insult. The results will have clinical relevance to conditions of myocardial ischemia and systemic hypoxemia, therapeutic interventions to treat these conditions, and consequences of reoxygenation of hypoxic myocardium.

对冠状动脉和生理机制的研究 提出了对非缺血性和缺血性缺氧的心肌反应。 这 麻醉狗的左前冠状动脉将是 灌注受控氧含量（非缺血性缺氧）或 它的流动被阻塞（缺血性缺氧）。 血液将通过 体外犬肺。 冠状动脉和静脉氧张力 含量，血流（流量计和微球分布）， 心肌氧张力（光学技术），收缩功能 （超声段长度仪），核苷的浓度和高浓度 将测量能量磷酸盐（HPLC）和心外膜电图。 心肌氧供应/需求关系的扰动将是 在非缺血缺氧期间进行的，以区分由于 由于血管活性代谢物而导致的氧气不足。 这些 通过在非缺血性期间确定机制将进一步阐明 缺氧的药物的作用改变了血管扩张剂对简短的反应 缺血和/或外源腺苷（腺苷脱氨酶，氨基氨叶素， 二吡啶胺，硝苯地平）。 决定恢复速率的机制 心肌缺氧后的血管张力还将进行研究。 进一步的研究将确定非缺血性的长期（4小时）效应 心肌缺氧在冠状动脉血流动力学参数上（区域流动，小 血液体积，附带电导）和心肌收缩 核苷和高能磷酸盐的功能和浓度。 经过 将这些发现与类似时期之后的测量结果进行比较 缺血性缺氧，缺氧本身的重要性和代谢物积累 长期缺血将被定义。 恢复冠状动脉 血液动力学功能，心肌收缩功能和浓度 核苷和高能磷酸盐在重氧过程中 将确定并进行比较 在再灌注期间恢复这些参数之后 缺血性缺氧时期。 调查与长期相符 术语目标1）定义调整冠状动脉血流的机制 满足心肌氧的要求； 2）定义 这些机制对缺血和低氧损伤。 结果将有 与心肌缺血和全身性的临床相关性 低氧血症，治疗这些疾病的治疗干预措施，以及 低氧心肌重氧的后果。