Mild hypothermia alleviates cardiomyocyte necroptosis after cardiopulmonary resuscitation by regulating TRPV1

Abstract Background Therapeutic mild hypothermia (MH) is expected to improve the neurological outcome and the survival rate of CPR after cardiac arrest (CA). However, whether and how mild hypothermia protects cardiomyocytes largely remains to be explored. Methods Three to four-month-old (age), 319.1-480.0 g (weight), male (sex) Wistar rats were randomly divided into normothermia (NT) groups (acceptable range, 36.0-38.0°C) and MH groups (acceptable range, 32-34°C). Then ten minutes after CA, CPR was perfumed by a slow injection of 0.30-0.50 mL epinephrine solution (30.00 μg/mL). Moreover, to test the effect of TRPV1, capsaicin was injected through the right femoral artery both in NT groups and MH groups. Results We found that MH improved the recovery of spontaneous breathing, increased survival rate, and inhibited cardiac necroptosis of Wistar rats after CPR. Moreover, MH alleviated primary cardiomyocytes necroptosis after oxygen-glucose deprivation and reperfusion through up-regulating TRPV1, down-regulating EGFR, and subsequently suppressing MLKL. Furthermore, capsaicin, the TRPV1-activator, combined with MH, improved the blood pressure of Wistar rats after CPR when compared with MH alone. Capsaicin improved the spontaneous breathing rate and survival rate of Wistar rats after CPR. Conclusions MH may protect cardiac function by TRPV1-inhibited cardiomyocyte necroptosis.