Effect of adenosine receptor blockade: preventing protective preconditioning depends on time of initiation.
Effect of adenosine receptor blockade: preventing protective preconditioning depends on time of initiation.
复制标题
腺苷受体阻断的效果：防止保护性预适应取决于起始时间。
DOI：
10.1152/ajpheart.1993.265.2.h504
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Downey,JM
中科院分区：
文献类型：
--
作者：
Thornton,JD;Thornton,CS;Downey,JM
缺血预处理可保护兔心肌免受缺血再灌注损伤，腺苷受体参与了这种保护作用。本研究试图通过在研究期间的不同时间点输注腺苷受体拮抗剂PD-115，199来确定何时必须占据腺苷受体以实现保护。开胸兔进行30分钟的局部缺血，然后再灌注3小时，风险区有38 +/- 4%的梗死。当心脏预处理5分钟缺血和10分钟再灌注前30分钟的缺血期，只有9 +/- 2%的梗死发生。在缺血预处理发作前5分钟给予PD-115，199阻断了预处理的保护作用（39 +/- 5%梗死）。PD-115，199在缺血预处理事件和30分钟缺血期间（30 +/- 4%梗死）给药时也阻断了保护作用。在缺血30分钟结束时给予PD-115，199不会阻断预处理（PC）心脏的保护作用（17 +/- 5%梗死），对非PC心脏无影响（44 +/- 6%梗死）。在以往的研究中，我们发现外源性腺苷可以替代缺血对心脏进行预适应，提示腺苷是预适应的启动剂。然而，这些结果表明，腺苷受体也必须占用在长时间的缺血预处理是保护性的，并建议腺苷是预处理的介质以及。
Ischemic preconditioning protects the rabbit myocardium from infarction from a subsequent ischemia, and adenosine receptors appear to be involved in this protection. The present study attempts to determine when adenosine receptors must be occupied to achieve protection by infusing the adenosine receptor antagonist PD-115,199 at various time points during the study. Open-chest rabbits were subjected to 30 min of regional ischemia followed by 3 h of reperfusion and had 38 +/- 4% infarction of the risk zone. When hearts were preconditioned by 5 min of ischemia and 10 min reperfusion before the 30-min period of ischemia, only 9 +/- 2% infarction occurred. PD-115,199 given 5 min before the ischemic preconditioning episode blocked the protective effect of preconditioning (39 +/- 5% infarction). PD-115,199 also blocked the protection when given between the ischemic preconditioning episode and the 30-min period of ischemia (30 +/- 4% infarction). PD-115,199 given at the end of 30 min of ischemia did not block protection in preconditioned (PC) hearts (17 +/- 5% infarction) and had no effect on non-PC hearts (44 +/- 6% infarction). In prior studies we found that exogenous adenosine could substitute for ischemia to precondition the heart, indicating that adenosine is an initiator of preconditioning. These results, however, indicate that adenosine receptors must also be occupied during the long ischemic period for preconditioning to be protective and suggest that adenosine is a mediator of preconditioning as well.