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

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Abstract

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.

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Fig. 1

Data Availability

Original research data will be available upon request.

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Funding

The study was funded by the John S. Dunn Chair in Cardiology Research and Education.

Author information

Authors and Affiliations

  1. The Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Yochai Birnbaum

  2. University of Texas At Austin, Austin, TX, USA

    Regina Ye

  3. The Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Blvd, BSB 648, Galveston, TX, 77555, USA

    Yumei Ye

Authors
  1. Yochai Birnbaum
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  2. Regina Ye
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  3. Yumei Ye
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Contributions

All authors contributed to the study conception and design. Material preparation, experiments, and data collection were performed by Yumei Ye. Data analysis was performed by Yumei Ye and Yochai Birnbaum. Figures were made by Yochai Birnbaum. The first draft of the manuscript was written by Yochai Birnbaum, and all authors read and edited the manuscript. All three authors read and approved the final manuscript.

Corresponding author

Correspondence to Yumei Ye.

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Ethics Approval

The experimental designs and animal care were conducted in accordance with the Guide for the Care and Use of Laboratory Animals, published by the National Institutes of Health (NIH Publication No. 85–23, revised 1996) and approved by the Institutional Animal Care and Use Committee of the University of Texas Medical Branch.

Conflict of Interest

Yochai Birnbaum and Yumei Ye — research grant from AstraZeneca. Regina Ye – none.

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Birnbaum, Y., Ye, R. & Ye, Y. Aspirin Blocks the Infarct-Size Limiting Effect of Ischemic Postconditioning in the Rat. Cardiovasc Drugs Ther 37, 221–224 (2023). https://doi.org/10.1007/s10557-021-07241-8

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  • DOI: https://doi.org/10.1007/s10557-021-07241-8

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