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Updated: Aug 7, 2026
Model of Ischemia and Reperfusion Injury in Rabbits
Published on: November 3, 2023
Age- and gender-related differences in ischemia/reperfusion injury and cardioprotection: effects of diazoxide
James D McCully1, Yoshiya Toyoda, Hidetaka Wakiyama
1Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA. james_mccully@hms.harvard.edu
Insights
Aging reduces heart tolerance to ischemia. Cardioplegia protects mature hearts but is less effective in aged female hearts compared to aged male hearts, indicating a need for sex-specific protocols.
Area of Science:
- Cardiovascular Physiology
- Gerontology
- Pharmacology
Background:
- Aging impairs cardiac tolerance to ischemia.
- Aged female hearts exhibit greater susceptibility to ischemia than aged male hearts.
- Cardioplegia's efficacy in female hearts post-ischemia was previously unknown.
Purpose of the Study:
- To investigate the impact of age and gender on cardiac ischemia-reperfusion injury.
- To evaluate the effectiveness of cardioplegia +/- diazoxide in protecting male and female rabbit hearts from ischemia, considering age.
Main Methods:
- Langendorff perfusion of mature and aged male and female rabbit hearts.
- Global ischemia protocol (30 minutes) followed by reperfusion (120 minutes).
- Administration of cardioplegia +/- diazoxide before ischemia.
Main Results:
- Global ischemia worsened functional recovery and increased infarct size in all groups.
- Aged hearts showed exacerbated ischemia effects compared to mature hearts.
- Cardioplegia improved recovery and reduced infarct size in mature hearts but was less effective in aged hearts, particularly aged females.
Conclusions:
- Age significantly impacts post-ischemic recovery and infarct size.
- Cardioplegia's cardioprotective effects are influenced by age and gender, with a notable age-by-gender interaction.
- Current cardioplegia protocols optimized for males are less effective in aged female hearts.
Background:
Recent studies have demonstrated that aging is associated with reduced tolerance to ischemia and that the aged (not senescent) female heart has greater susceptibility to ischemia as compared with the aged male heart. Previously, we have shown that ischemia can be modulated with cardioplegia in the male heart; however, efficacy in the female heart was unknown.
Methods:
In this study, male and female mature (15 to 20 weeks) aged (>32 months) rabbit hearts (n = 134) were subjected to Langendorff perfusion. Control hearts were perfused for 180 minutes. Global ischemia hearts received 30 minutes of equilibrium, 30 minutes of global ischemia, and 120 minutes of reperfusion. Cardioplegia +/- diazoxide was infused separately, 5 minutes before global ischemia.
Results:
Global ischemia significantly decreased postischemic functional recovery and significantly increased infarct size in the mature and aged male and female heart (p < 0.05 versus control). The effects of global ischemia were significantly exacerbated (p < 0.05) in the aged heart as compared with the mature heart. Cardioplegia +/- diazoxide significantly increased postischemic functional recovery and significantly decreased infarct size in mature male and female hearts, but these effects were significantly decreased in the aged heart (p < 0.05) and in the aged female as compared with the aged male heart.
Conclusions:
Postischemic functional recovery and infarct size are affected by age but not by gender. The cardioprotection afforded by cardioplegia is affected by age and gender with a strong age-by-gender interaction for end-diastolic pressure and infarct size. Our results indicate that currently optimized cardioplegia protocols effective in the male heart are not as efficacious in the aged female heart.
