Canagliflozin attenuates post-resuscitation myocardial dysfunction in diabetic rats by inhibiting autophagy through the PI3K/Akt/mTOR pathway
Qihui Huang,
Wei Shi,
Minjie Wang,
Liangliang Zhang,
Yijun Zhang,
Yan Hu,
Sinong Pan,
Bingrui Ling,
Huaqing Zhu,
Wenyan Xiao,
Tianfeng Hua,
Min Yang
Affiliations
Qihui Huang
The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China
Wei Shi
The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China
Minjie Wang
The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China
Liangliang Zhang
The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China
Yijun Zhang
The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China
Yan Hu
The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China
Sinong Pan
The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China
Bingrui Ling
The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China
Huaqing Zhu
Laboratory of Molecular, Biology and Department of Biochemistry, Anhui Medical University, Hefei 230022, Anhui, People’s Republic of China
Wenyan Xiao
The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China
Tianfeng Hua
The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China; Corresponding author
Min Yang
The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, People’s Republic of China; Corresponding author
Summary: This study investigated the effects of canagliflozin on myocardial dysfunction after cardiac arrest and cardiopulmonary resuscitation in diabetic rats and the underlying mechanisms. Male rats with type 2 diabetes mellitus (T2DM) were subjected to a modified epicardial fibrillation model. Pretreatment with canagliflozin (10 mg/kg/day) for four weeks improved ATP levels, post-resuscitation ejection fraction, acidosis, and hemodynamics. Canagliflozin also reduced myocardial edema, mitochondrial damage and, post-resuscitation autophagy levels. In vitro analyses showed that canagliflozin significantly reduced reactive oxygen species and preserved mitochondrial membrane potential. Using the PI3K/Akt pathway inhibitor Ly294002, canagliflozin was shown to attenuate hyperautophagy and cardiac injury induced by high glucose and hypoxia-reoxygenation through activation of the PI3K/Akt/mTOR pathway. This study highlights the therapeutic potential of canagliflozin in post-resuscitation myocardial dysfunction in diabetes, providing new insights for clinical treatment and experimental research.
