Cardioprotection by Mild Hypothermia Is Abolished in Aged Mice.

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.