Aspirin Blocks the Infarct-Size Limiting Effect of Ischemic Postconditioning in the Rat

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.

Automated summary

Aspirin loading may explain the lack of success of ischemic postconditioning in clinical practice.