Mild hypothermia alleviates cardiomyocyte necroptosis after cardiopulmonary resuscitation by regulating TRPV1

Background Therapeutic mild hypothermia (MH) is expected to improve the neurological outcome and the survival rate of CPR after cardiac arrest (CA). However, the mechanisms by which MH protects cardiomyocytes remain largely unexplored. Methods In this study, three- to four-month-old male Wistar rats, weighing between 319.1 and 480.0 grams, were randomly divided into normothermia (NT) groups (acceptable range, 36.0-38.0°C) and MH groups (acceptable range, 32-34°C). Ten minutes after CA, CPR was perfumed with a slow injection of 0.30-0.50 mL epinephrine solution (30.00 μg/mL). Moreover, to investigate the role of TRPV1, capsaicin was administered through the right femoral artery in both NT and MH groups. Results We found that MH improved the spontaneous breathing recovery, increased survival rate, and inhibited cardiac necroptosis in Wistar rats after CPR. Additionally, MH alleviated primary cardiomyocytes necroptosis after oxygen-glucose deprivation and reperfusion through upregulating TRPV1, downregulating EGFR, and subsequently suppressing MLKL. Furthermore, the combination of capsaicin, a TRPV1 activator, with MH enhanced blood pressure in Wistar rats after CPR compared to MH alone. Capsaicin improved the spontaneous breathing rate and survival rate of Wistar rats after CPR. Conclusions MH may protect cardiac function by mitigating cardiomyocyte necroptosis through regulating TRPV1.