Background

Ischemic postconditioning (PostC), repetitive cycles of re-occlusion, and reperfusion of the infarct-related artery immediately after reperfusion have been shown to limit myocardial infarct size in various animal models. Yet, translating the model into the clinical setting was disappointing, several clinical trials showing neutral effect. We hypothesized that aspirin loading could explain the differences between the pre-clinical and clinical studies.

Methods

Male Sprague Dawley rats were subjected to 30-min coronary artery ligation. At 25 min of ischemia, animals received intravenous aspirin (20 mg/kg) or vehicle. Upon reperfusion half of the rats were randomized to PostC (3 cycles of 10-s re-occlusion/10-s reperfusion. After 4-h reperfusion, rats were euthanized. Area at risk was assessed by blue dye and infarct size by 2,3,5-triphenyl-tetrazolium-chloride (TTC).

Results

Body weight and the size of the ischemic area at risk were comparable among groups. Infarct size expressed as a percentage of the ischemic area at risk was significantly smaller in the PostC group (13.9 ± 0.4%; p < 0.001) compared to the control group (31.0 ± 2.2%). Aspirin alone had no effect on infarct size (29.0 ± 2.6%). Yet, aspirin completely blocked the protective effect of PostC (33.3 ± 1.1%).

Conclusions

Aspirin, administered before reperfusion, blocks the infarct size limiting effects of PostC in the rat.

中文翻译：

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阿司匹林阻断大鼠缺血后处理对梗死面积的限制作用

背景

在各种动物模型中，缺血后处理（PostC）、再闭塞的重复循环以及梗塞相关动脉在再灌注后立即再灌注已被证明可以限制心肌梗塞的大小。然而，将该模型转化为临床环境的结果令人失望，一些临床试验显示出中性效果。我们假设阿司匹林负荷可以解释临床前研究和临床研究之间的差异。

方法

雄性 Sprague Dawley 大鼠接受 30 分钟的冠状动脉结扎。缺血 25 分钟后，动物接受静脉注射阿司匹林 (20 mg/kg) 或载体。再灌注后，一半大鼠被随机分配至 PostC（3 个周期，10 秒再闭塞/10 秒再灌注。再灌注 4 小时后，对大鼠实施安乐死。通过蓝色染料评估危险区域，并通过 2 评估梗塞面积， 3,5-三苯基氯化四唑（TTC）。

结果

各组之间的体重和缺血风险区域的大小具有可比性。 与对照组 (31.0 ± 2.2%) 相比，PostC 组的梗死面积（以缺血风险区域的百分比表示）显着较小 (13.9 ± 0.4%；p < 0.001)。单独使用阿司匹林对梗塞面积没有影响（29.0 ± 2.6%）。然而，阿司匹林完全阻断了 PostC 的保护作用 (33.3 ± 1.1%)。

结论

再灌注前给予阿司匹林，可阻断 PostC 对大鼠的梗死面积限制作用。