Quantitative relation between interstitial adenosine concentration and coronary blood flow.
Quantitative relation between interstitial adenosine concentration and coronary blood flow.
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DOI：
10.1161/01.res.79.3.601
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发表时间：
1996-09
影响因子：
20.1
通讯作者：
David W. Stepp;Richard Van Bibber;Keith Kroll;E. Feigl
中科院分区：
文献类型：
--
作者：
David W. Stepp;Richard Van Bibber;Keith Kroll;E. Feigl
外源性和内源性腺苷在控制冠状动脉血流中的作用使用心肌的轴向分布数学模型来确定，以从冠状动脉和静脉腺苷值估计间质腺苷浓度。在闭胸麻醉犬中，以恒定压力灌注左冠状动脉主干，并在冠状动脉内注入外源性腺苷以增加冠状动脉流量。基础间质腺苷为92 nmol/L，刚好处于增加冠状动脉血流的阈值。间质腺苷浓度仅增加62%就足以使冠状动脉流量从最大流量的5%增加到50%。通过比较对外源性冠状动脉内腺苷输注的反应与通过抑制腺苷激酶和腺苷脱氨酶产生的内源性腺苷的增加，测试了继发于内皮细胞上腺苷受体活化的内皮扩张剂的可能贡献。如果腺苷通过内皮机制增加冠状动脉流量，则由于假定的额外内皮扩张剂，外源性腺苷的间质ED 50将低于内源性腺苷。外源性腺苷的间质ED 50为156 nmol/L，与内源性ED 50 150 nmol/L无差异。总之，基础间质腺苷浓度处于增加冠状动脉血流量的显著陡峭剂量反应曲线的阈值。没有证据表明，在体内内皮细胞的腺苷受体激活继发于内皮介导的血管扩张机制。陡峭的腺苷剂量反应曲线表明，腺苷浓度的测量应谨慎解释，因为腺苷浓度的微小变化会导致冠状动脉血流的巨大变化。
The effect of exogenous and endogenous adenosine in controlling coronary flow was determined using an axially distributed mathematical model of the myocardium to estimate interstitial adenosine concentration from coronary arterial and venous adenosine values. The left main coronary artery was perfused at constant pressure in closed-chest, anesthetized dogs, and exogenous adenosine was infused intracoronary to increase coronary flow. Basal interstitial adenosine was 92 nmol/L, just at the threshold for increasing coronary flow. An increase in interstitial adenosine concentration of only 62% was sufficient to increase coronary flow from 5% to 50% of maximal flow. The possible contribution of an endothelial dilator secondary to activation of adenosine receptors on endothelial cells was tested by comparing the response to exogenous intracoronary adenosine infusion with increases in endogenous adenosine produced by inhibition of adenosine kinase and adenosine deaminase. If adenosine increases coronary flow by an endothelial mechanism, then the interstitial ED50 of exogenous adenosine would be lower than that for endogenous adenosine due to the postulated additional endothelial dilator. The interstitial ED50 for exogenous adenosine was 156 nmol/L, not different from the endogenous ED50 of 150 nmol/L. In conclusion, basal interstitial adenosine concentration is at the threshold of a remarkably steep dose-response curve for increasing coronary blood flow. No evidence was found for an endothelium-mediated vasodilator mechanism secondary to adenosine receptor activation of endothelial cells in vivo. The steep adenosine dose-response curve indicates that measurements of adenosine concentration should be interpreted with caution, because small changes in adenosine concentration cause large changes in coronary flow.