2. Academic Validation
  3. Targeted temperature management alleviates post-resuscitation myocardial dysfunction by inhibiting ferroptosis

Targeted temperature management alleviates post-resuscitation myocardial dysfunction by inhibiting ferroptosis

  • Cell Death Discov. 2025 Feb 21;11(1):71. doi: 10.1038/s41420-025-02356-5.
Yingying Zhang # 1 2,  Weiwei Du # 1 2,  Ting Kong # 2 3,  Tianfeng Hua 2 4,  Honghao Ma 1 2,  Yan Hu 2 4,  Sinong Pan 2 4,  Bingrui Ling 2 4,  Min Yang 5 6,  Cheng Cheng 7 8 9
Affiliations

Affiliations

  • 1 Department of Cardiology, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China.
  • 2 The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China.
  • 3 Department of General Practice Department, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China.
  • 4 The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China.
  • 5 The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China. yangmin@ahmu.edu.cn.
  • 6 The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China. yangmin@ahmu.edu.cn.
  • 7 Department of Cardiology, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China. chengcheng@ahmu.edu.cn.
  • 8 The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China. chengcheng@ahmu.edu.cn.
  • 9 Department of Cardiology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230088, Anhui, China. chengcheng@ahmu.edu.cn.
  • # Contributed equally.
PMID: 39984437 DOI: 10.1038/s41420-025-02356-5
Abstract

Targeted temperature management (TTM) is a vital intervention for cardiac arrest survivors to mitigate post-resuscitation myocardial dysfunction (PRMD). However, the optimal temperature for TTM remains a topic of debate. This study investigates the effects of TTM at different temperatures and explores the underlying mechanisms using in vivo and in vitro models of myocardial ischemia/reperfusion (I/R) injury following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). We found that TTM at 33 °C significantly improved post-resuscitation hemodynamics and myocardial function, reducing both myocardial and mitochondrial damage in the rat model of CA/CPR. Additionally, Deferoxamin (DFO), as an iron chelating agent, also demonstrated protective effects against PRMD. Both in vitro and in vivo experiments confirmed that hypothermia at 33 °C and DFO mitigated mitochondrial damage, oxidative stress, lipid peroxidation, and iron overload, while suppressing ferritinophagy and Ferroptosis. Furthermore, TTM at 33 °C and DFO facilitated the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), with Nrf2 activation leading to inhibited ferritinophagy and enhanced iron export. Our findings indicate that TTM at 33° C, as opposed to 36° C, significantly alleviates PRMD and reduced myocardial damage by inhibiting Ferroptosis. Theses protective effects are associated with Nrf2 activation and modulation of iron homeostasis. Moreover, DFO not only suppressed Ferroptosis through its iron chelation properties but also by activating the Nrf2 axis.

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