Interstitial purine metabolites and lactate during regional myocardial hypoxia.

Interstitial purine metabolites and lactate during regional myocardial hypoxia.
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局部心肌缺氧期间的间质嘌呤代谢物和乳酸。

DOI:
10.1093/cvr/27.8.1498
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发表时间:
1993
影响因子:
10.8
通讯作者:
Downey,HF
Downey,HF
中科院分区:
医学1区
文献类型:
--
作者:
VanWylen,DG;WilliamsJr,AG;Downey,HF

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目的:腺苷是一种众所周知的血管扩张剂,据信有助于冠状循环的代谢调节。本研究的目的是评估长时间局部非缺血性心肌缺氧期间间质液腺苷、腺苷代谢物和乳酸的变化。方法:为了诱导局部缺氧,通过体外循环对麻醉犬(n=9)左冠状动脉前降支进行恒压(100 mm Hg)灌注脱氧血(PO2≍2.6 kPa)60 min。分流。采用心脏微透析法采集心脏间质液,以透析液代谢物水平作为间质液浓度指标。结果:缺氧时,冠脉血流量增加3.9倍,而心肌耗氧量保持相对恒定。局部缺氧期间,整体心脏功能、全身动脉压或心率没有变化,表明缺氧刺激不会增强交感神经系统活动。透析液腺苷在缺氧期间的任何时间点均不增加,但在缺氧25分钟后减少。在缺氧的前 10 分钟内,透析液中肌苷、次黄嘌呤和黄嘌呤的水平短暂增加,而透析液乳酸持续增加。在存在腺苷脱氨酶抑制剂赤9-(2-羟基-3-壬基)腺嘌呤的情况下,腺苷是主要的嘌呤代谢物,并且在缺氧期间短暂增加。结论:在缺氧期间,通过腺苷产生和降解途径的通量短暂增加。然而,间质液腺苷缺乏增加并不支持腺苷在局部心肌缺氧的持续充血反应中的作用。心血管研究1993; 27:1498-1503
Objective:Adenosine is a well known vasodilator believed to contribute to metabolic adjustments of the coronary circulation. The purpose of this study was to assess changes in interstitial fluid adenosine, adenosine metabolites, and lactate during prolonged regional, non-ischaemic myocardial hypoxia.Methods:To induce regional hypoxia, the left anterior descending coronary artery of anaesthetised dogs (n=9) was perfused at constant pressure (100 mm Hg) with deoxygenated blood (PO2≍2.6 kPa) for 60 min via an extracorporeal shunt. Cardiac interstitial fluid was sampled by cardiac microdialysis, using dialysate metabolite levels as indices of interstitial fluid concentrations.Results:During hypoxia, coronary blood flow increased 3.9-fold, while myocardial oxygen consumption was maintained relatively constant. There were no changes in global cardiac function, systemic arterial pressure, or heart rate during regional hypoxia, indicating that the hypoxic stimulus did not augment sympathetic nervous system activity. Dialysate adenosine was not increased at any point of the hypoxic period, but was decreased by 25 min hypoxia. Dialysate levels of inosine, hypoxanthine, and xanthine were increased transiently during the first 10 min of hypoxia while there was a sustained increase in dialysate lactate. In the presence of erythro-9-(2-hydroxy-3-nonyl) adenine, an adenosine deaminase inhibitor, adenosine was the predominant purine metabolite and increased transiently during hypoxia.Conclusions:Flux through the adenosine production and degradation pathways is transiently increased during hypoxia. However, the lack of an increase in interstitial fluid adenosine does not support a role for adenosine in the sustained hyperaemic response to regional myocardial hypoxia.Cardiovascular Research1993; 27:1498-1503