Van Wylen D G, Williams A G, Downey H F
Department of Physiology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo 14215.
Cardiovasc Res. 1993 Aug;27(8):1498-503. doi: 10.1093/cvr/27.8.1498.
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.
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 approximately 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.
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.
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.
腺苷是一种众所周知的血管扩张剂，被认为有助于冠状动脉循环的代谢调节。本研究的目的是评估在长时间局部非缺血性心肌缺氧期间组织间液中腺苷、腺苷代谢产物和乳酸的变化。
为诱导局部缺氧，对9只麻醉犬的左前降支冠状动脉通过体外分流以恒定压力（100 mmHg）灌注脱氧血液（PO2约为2.6 kPa）60分钟。通过心脏微透析采集心脏组织间液，以透析液代谢产物水平作为组织间液浓度的指标。
缺氧期间，冠状动脉血流量增加了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、体动脉压或心率均无变化，表明缺氧刺激并未增强交感神经系统活动。在缺氧期的任何时间点，透析液中的腺苷均未增加，但在缺氧25分钟时有所下降。在缺氧的前10分钟内，透析液中的肌苷、次黄嘌呤和黄嘌呤水平短暂升高，而透析液中的乳酸则持续增加。在存在腺苷脱氨酶抑制剂erythro-9-(2-hydroxy-3-nonyl) adenine的情况下，腺苷是主要的嘌呤代谢产物，并且在缺氧期间短暂增加。
在缺氧期间，腺苷生成和降解途径的通量短暂增加。然而，组织间液中腺苷未增加并不支持腺苷在对局部心肌缺氧的持续充血反应中起作用。
