Related Experiment Video
Updated: Mar 3, 2026
In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
Published on: October 27, 2020
Cardioprotection by Mild Hypothermia Is Abolished in Aged Mice
Junjie Guo1,2, Shuning Zhang1, Leilei Ma1
11 Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University , Shanghai, China .
Abstract:
Mild hypothermia (MH) renders the hearts resistant to ischemia/reperfusion (IR) injury in animal experiments. Unexpectedly, this effect was not observed in recent clinical trials. The aged hearts in mice have been demonstrated to be more susceptible to IR injury. This study aimed to examine whether the cardioprotection of MH was abolished in aged mice. Young (Y, 3 months old) and aged (A, 20 months old) male C57BL/6 mice were randomized into six groups. Sham (Y-SHAM and A-SHAM) and control (Y-CON+IR and A-CON+IR) animals maintained core body temperature at 37°C ± 0.5°C; MH groups (Y-MH+IR and A-MH+IR) received surface cooling and kept core body temperature at 32-35°C before ischemia until reperfusion. The IR mice underwent 40 minutes of ischemia followed by 24 hours of reperfusion. Finally, the cardiac function and infarct size (IS) were evaluated. The A-CON+IR group exhibited more severe cardiac dysfunction compared with the Y-CON+IR group showing as decreased ejection fraction (EF) (34.8% ± 8.5% vs. 44.2% ± 5.9%) and fraction shortening (FS) (15.2% ± 4.1% vs. 21.8% ± 3.7%). MH restored EF to 55.3% ± 6.1% and FS to 28.5% ± 3.6% in the Y-MH+IR group but not in the A-MH+IR group. Similarly, IS was significantly increased in the A-CON+IR group compared with the Y-CON+IR group (54.5% ± 10.6% vs. 42.0% ± 6.4%). MH lessened the IS to 21.3% ± 7.6% in the Y-MH+IR group but not in the A-MH+IR group. Thus, the cardioprotection rendered by MH is abolished in aged mice.
Insights
Mild hypothermia (MH) protects young mouse hearts from ischemia/reperfusion (IR) injury, but this protective effect is lost in aged mice. This suggests age impacts MH
Area of Science:
- Cardiovascular Science
- Gerontology
- Therapeutic Hypothermia
Background:
- Mild hypothermia (MH) is known to protect the heart against ischemia/reperfusion (IR) injury in animal models.
- Recent clinical trials have not consistently observed this cardioprotective effect of MH.
- Aged hearts are more susceptible to IR injury, prompting an investigation into age-related efficacy of MH.
Purpose of the Study:
- To investigate whether the cardioprotective effects of mild hypothermia (MH) are abolished in aged mice.
- To compare the susceptibility of young and aged mouse hearts to ischemia/reperfusion (IR) injury.
- To evaluate the impact of MH on cardiac function and infarct size in aged versus young mice.
Main Methods:
- Young (3-month-old) and aged (20-month-old) male C57BL/6 mice were used.
- Mice were subjected to 40 minutes of ischemia followed by 24 hours of reperfusion, with or without mild hypothermia (core body temperature 32-35°C).
- Cardiac function (ejection fraction, fraction shortening) and infarct size were assessed.
Main Results:
- Aged mice (A-CON+IR) showed significantly worse cardiac dysfunction (lower EF and FS) and larger infarct sizes compared to young mice (Y-CON+IR).
- Mild hypothermia (MH) significantly improved cardiac function and reduced infarct size in young mice (Y-MH+IR).
- Mild hypothermia (MH) failed to provide cardioprotection in aged mice (A-MH+IR), with no significant improvement in cardiac function or infarct size compared to aged controls.
Conclusions:
- The cardioprotective effect of mild hypothermia (MH) against ischemia/reperfusion (IR) injury is abolished in aged mice.
- Age significantly exacerbates cardiac susceptibility to IR injury.
- These findings highlight the importance of age as a factor in the efficacy of therapeutic hypothermia for cardiac protection.
