Differential effects of adenosine preconditioning on the postischemic rat myocardium.
Differential effects of adenosine preconditioning on the postischemic rat myocardium.
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腺苷预处理对缺血后大鼠心肌的不同影响。
DOI：
10.1006/jsre.1996.0359
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Harken,AH
中科院分区：
文献类型：
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作者：
Meldrum,DR;ClevelandJr,JC;Sheridan,BC;Rowland,RT;Banerjee,A;Harken,AH
缺血预适应是针对持续性缺血再灌注损伤(I/R)的内源性心肌保护现象。尽管短暂性缺血的复杂刺激诱导了对酸中毒、梗死和顿抑的全局心肌保护，但尚不清楚短暂性缺血的特定成分(如腺苷)是否负责不同方面的保护。为研究这一点，大鼠离体心在全心肌I/R前10分钟(20分钟/40分钟；37℃)用腺苷(12 5μ冠脉浓度)或赋形剂(预适应)处理。为了确定腺苷是否影响顿抑，获得了连续的功能数据(心率、压力乘积和冠脉流量)。为了确定腺苷是否影响坏死，在缺血后复流过程中，测定了冠脉流出物中肌酸激酶(CK)的丢失。为了确定腺苷是否影响pH，使用核磁共振进行了连续的pH测量。结果表明，腺苷对晕厥有保护作用，但对酸中毒的保护作用很小。尽管有严重的酸中毒，腺苷仍能起到保护作用。腺苷不能限制CK的丢失。我们得出的结论是：(1)腺苷预适应是缺血预适应的一个组成部分，可以保护大鼠I/R后的心肌功能，但不能提供针对I/R的整体心肌保护；(2)即使发生严重的缺血性酸中毒，功能也可以得到保护；(3)即使在同等程度的缺血后CK丢失，功能也可以得到保护。这些结果表明，药物预适应可能需要多种药物才能提供全局心肌保护。
Ischemic preconditioning describes the phenomenon of endogenous myocardial protection against sustained ischemia-reperfusion injury (I/R). Although the complex stimulus of transient ischemia induces global myocardial protection against acidosis, infarction, and stunning, it is unknown whether select components of transient ischemia (e.g., adenosine) are responsible for different aspects of protection. To study this, isolated rat hearts were treated with adenosine (125 μMcoronary concentration) or vehicle 10 min prior (preconditioning) to global myocardial I/R (20 min/40 min; 37°C). To determine whether adenosine affects stunning, continuous functional data (rate pressure product and coronary flow) were obtained. To determine whether adenosine affects necrosis, creatine kinase (CK) loss into the coronary effluent was determined during postischemic reflow. To determine whether adenosine affects pH, continuous pH measurements were made using NMR. Results indicate that adenosine protects against stunning but provides only minimal protection against acidosis. Adenosine's protection of function occurs despite severe acidosis. Adenosine does not limit CK loss. We conclude that (1) adenosine preconditioning, a component of ischemic preconditioning, protects myocardial function following I/R, but does not provide global myocardial protection against I/R in the rat; (2) protection of function can occur despite severe ischemic acidosis; and (3) protection of function occurs despite equivalent postischemic CK loss. These results suggest that pharmacologic preconditioning may require multiple agents in order to provide global myocardial protection.