REGIONAL NONISCHEMIC MYCOARDIAL HYPOXIA

局部非缺血性心肌缺氧

基本信息

批准号：
2702170
负责人：
HARRY FRED DOWNEY
金额：
$ 22.46万
依托单位：
UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-04-01 至 2001-04-30
项目状态：
已结题

项目摘要

A continuing investigation of right coronary (RC) hemodynamics and right ventricular (RV) metabolic and contractile function is proposed. The investigation will focus on mechanisms which modulate RC blood flow and RV function during perturbations of myocardial 02 supply/demand balance. In the working, in situ canine RV, the investigation will delineate: l) Mechanisms by which changes in RC perfusion pressure alter RV O2 demand; 2) Relative contributions of myocardial PO2 and vasoactive metabolites, especially adenosine, in regulation of RC blood flow; 3) Relative contributions of RC flow and 02 extraction reserves in supplying 02 to RV myocardium when RC arterial 02 content is selectively reduced; 4) Relative potencies of alpha adrenoceptor subtypes in the RC circulation and their respective roles in RC pressure-flow autoregulation, modulation of RC 02 extraction reserve, and possible limitation of RV 02 supply. RV energetics will be evaluated to define subcellular adjustments triggered by states of 02 deficiency and providing for metabolic control of coronary blood flow and for modulation of RV 02 demand. To further investigate pressure-flow autoregulation in the RC circulation, additional experiments will be conducted in a chronically instrumented canine model. With this model in the conscious state, RC blood flow will be measured as RC perfusion pressure is reduced by an adjustable constrictor implanted on the RC artery. Variables to be measured (as appropriate for the respective models): 1) RC blood flow and its transmural distribution (flowmeter and microsphere distribution); 2) RC arterial and venous 02 tension and content; 3) RC arterial and venous lactate concentrations (enzymatic techniques); 4) RC small vessel and total vascular volumes (isotope dilution); 5) right atrial and RV pressures and RV dP/dt; 6) heart rate; 7) systemic and pulmonary arterial pressures; 8) RV regional segment length and isometric force for computing regional segment shortening, work, and systolic stiffness; 9) RV P02 (intramyocardial polarographic electrode and RC venous P02); 10) high energy phosphates in RV biopsy samples (enzymatic techniques); 11) extracellular volume (sucrose distribution space); 12) nucleosides and lactate in RV biopsy samples and in RV myocardial microdialysis samples (HPLC and enzymatic techniques). The investigation is in accordance with long term objectives to define mechanisms which balance myocardial 02 supply/demand under changing conditions of 02 demand and supply, especially in the right ventricle. Results will impact clinical treatment for conditions of altered myocardial 02 supply relative to 02 demand.

右冠状动脉（RC）血流动力学和右持续调查提出了心室（RV）代谢和收缩功能。这调查将重点放在调节RC血流和RV的机制上心肌02供应/需求余额的扰动期间的功能。在工作原位犬RV的调查将描绘：L） RC灌注压力改变RV O2需求的机制； 2）心肌PO2和血管活性代谢物的相对贡献，特别是腺苷，调节RC血流； 3）相对 RC流量的贡献和02提取储备在向RV提供02方面的贡献当RC动脉02含量选择性降低时，心肌； 4）相对 RC循环中的α肾上腺素受体亚型的效力及其在RC压力流动调节中的各自作用，RC 02的调制提取储备，以及RV 02电源的可能限制。 RV 将评估能量学以定义触发的亚细胞调整通过02的状态，为冠状动脉的代谢控制提供了血流和调节RV 02需求。进一步调查 RC循环中的压力流动调节，其他实验将在长期仪器的犬模型中进行。与此在有意识状态下的模型，RC血流将被测量为RC 通过植入的可调节收缩器降低灌注压力 RC动脉。要测量的变量（适合相应模型）：1）RC血流及其透射分布（流量计和微球分布）； 2）RC动脉和静脉02张力和内容; 3）RC动脉和静脉乳酸浓度（酶促的技术）; 4）RC小容器和总血管体积（同位素稀释）; 5）右图和RV压力以及RV DP/DT； 6）心率； 7）全身和肺动脉压； 8）RV区域部分用于计算区域段缩短的长度和等距力，工作和收缩期僵硬； 9）RV P02（心脏内膜内一照表电极和RC静脉P02）; 10）RV活检中的高能磷酸盐样品（酶促技术）； 11）细胞外体积（蔗糖分销空间）; 12）RV活检样品中的核苷和乳酸在RV心肌透析样品（HPLC和酶促技术）中。调查符合长期目标的定义在更改下的心肌02供应/需求之间平衡的机制 02需求和供应的条件，尤其是在右心室中。结果将影响改变的临床治疗心肌02相对于02需求。