Adenosine kinetics in canine coronary circulation.
Adenosine kinetics in canine coronary circulation.
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犬冠状循环中的腺苷动力学。
DOI：
10.1152/ajpheart.1996.270.4.h1469
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Stepp,DW
中科院分区：
文献类型：
--
作者：
Kroll,K;Stepp,DW
采用多指示剂稀释法研究了腺苷在麻醉闭胸犬冠状循环中的动力学。在同时冠状动脉内推注125 I标记的白蛋白、[14 C]蔗糖和[3 H]腺苷期间，使用高效液相色谱和同位素检测技术，通过冠状静脉血自动采样测量稀释曲线。在对照条件下，与参比示踪剂[14 C]蔗糖相比，在冠状静脉样品中仅检测到1%的注射[3 H]腺苷，腺苷稀释曲线的峰值先于参比示踪剂的峰值2-4 s。优化模型拟合对照腺苷曲线需要结合高比率的毛细血管内皮细胞膜渗透性-表面积乘积与流量（5.3）和内皮细胞消耗能力与流量（23），以及广泛的流量异质性。稀释曲线在控制条件下，并在增加冠状动脉流量（硝酸甘油），抑制腺苷激酶（iodotubercidin），并封锁膜腺苷转运（潘生丁）。使用残差分析、灵敏度函数分析和Monte Carlo模拟技术确认了参数估计值的可靠性。在单独的实验中，非示踪剂腺苷注入冠状动脉和冠状静脉腺苷浓度的模型预测与测量值进行了比较，证实了模型的准确性。使用已发表的开胸犬冠状动脉血流量和动脉及冠状静脉血浆腺苷浓度的测量结果，估计体内间质腺苷浓度为100-220 nM。
Adenosine kinetics in the coronary circulation were investigated in anesthetized closed-chest dogs by analysis of multiple-indicator dilution experiments. During simultaneous intracoronary bolus injections of 125I-labeled albumin, [14C]sucrose, and [3H]adenosine, dilution curves were measured by automated sampling of coronary venous blood, using high-performance liquid chromatography and isotope detection techniques. Under control conditions, only 1% of the injected [3H]adenosine was detected in coronary venous samples, compared with the reference tracer, [14C]sucrose, and the peak of the adenosine dilution curve preceded those of the reference tracers by 2-4 s. Optimized model fits to the control adenosine curves required the combination of high ratios of the capillary endothelial cell membrane permeability-surface area product to flow (5.3) and endothelial cell consumption capacity to flow (23), in addition to a broad heterogeneity of flow. Dilution curves were measured under control conditions and during increased coronary flow (nitroglycerin), inhibition of the enzyme adenosine kinase (iodotubercidin), and blockade of membrane adenosine transport (dipyridamole). Reliability of the parameter estimates was confirmed using residual analysis, sensitivity function analysis, and Monte Carlo simulation techniques. Accuracy of the model was confirmed in separate experiments in which nontracer adenosine was infused into the coronary artery and the model prediction of coronary venous adenosine concentrations was compared with measured values. Using published measurements of coronary blood flow and arterial and coronary venous plasma adenosine concentrations in open-chest dogs, the estimated in vivo interstitial adenosine concentration is 100-220 nM.