Effects of canagliflozin preconditioning on post-resuscitation myocardial function in a diabetic rat model of cardiac arrest and cardiopulmonary resuscitation

Minjie Wang; Tianfeng Hua; Yijun Zhang; Qihui Huang; Wei Shi; Yuqian Chu; Yan Hu; Sinong Pan; Bingrui Ling; Wanchun Tang; Min Yang

doi:10.1016/j.ejphar.2024.177212

Effects of canagliflozin preconditioning on post-resuscitation myocardial function in a diabetic rat model of cardiac arrest and cardiopulmonary resuscitation

Eur J Pharmacol. 2024 Dec 18:988:177212. doi: 10.1016/j.ejphar.2024.177212. Online ahead of print.

Authors

Minjie Wang¹, Tianfeng Hua², Yijun Zhang³, Qihui Huang⁴, Wei Shi⁵, Yuqian Chu⁶, Yan Hu⁷, Sinong Pan⁸, Bingrui Ling⁹, Wanchun Tang¹⁰, Min Yang¹¹

Affiliations

¹ The Second Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Laboratory of Cardiopulmonary Resuscitation and Critical Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: wangminjie20220303@163.com.
² The Second Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Laboratory of Cardiopulmonary Resuscitation and Critical Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: huatianfeng@ahmu.edu.cn.
³ The Second Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Laboratory of Cardiopulmonary Resuscitation and Critical Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: 2145011585@stu.ahmu.edu.com.
⁴ The Second Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Laboratory of Cardiopulmonary Resuscitation and Critical Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: 2246010221@stu.ahmu.edu.com.
⁵ The Second Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Laboratory of Cardiopulmonary Resuscitation and Critical Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: 2045011520@stu.ahmu.edu.cn.
⁶ The Second Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Laboratory of Cardiopulmonary Resuscitation and Critical Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: 2145011649@stu.ahmu.edu.cn.
⁷ The Second Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Laboratory of Cardiopulmonary Resuscitation and Critical Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: huyan@stu.ahmu.edu.cn.
⁸ The Second Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Laboratory of Cardiopulmonary Resuscitation and Critical Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: 2245011816@stu.ahmu.edu.cn.
⁹ The Second Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Laboratory of Cardiopulmonary Resuscitation and Critical Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: 2245011812@stu.ahmu.edu.cn.
¹⁰ The Second Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Laboratory of Cardiopulmonary Resuscitation and Critical Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: wanchun.tang@vcuhealth.org.
¹¹ The Second Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Laboratory of Cardiopulmonary Resuscitation and Critical Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: yangmin@ahmu.edu.cn.

PMID: 39706464
DOI: 10.1016/j.ejphar.2024.177212

Abstract

Background: Canagliflozin can reduce the risk of cardiovascular disease in patients except for its targeted antidiabetic effects. However, it remains unknown whether canagliflozin alleviates the post-resuscitation myocardial dysfunction (PRMD) in type 2 diabetes mellitus.

Objective: To explore the effects and potential mechanisms of canagliflozin on myocardial function after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in a type 2 diabetic rat model.

Methods: Twenty-four type 2 diabetic rats were randomized into four groups: (1) sham + canagliflozin, (2) sham + placebo, (3) CPR + placebo, and (4) CPR + canagliflozin. Except for the sham + canagliflozin and placebo groups, both the CPR + placebo and canagliflozin groups underwent 8 min of CPR after the induction of ventricular fibrillation for 6 min. Myocardial function and hemodynamics were assessed at baseline and within 6 h after autonomous circulation (ROSC) return. Left ventricular tissues were sampled to determine the expressions of relevant proteins in the NLRP3 inflammasome pathway.

Results: The results demonstrated that the mean arterial pressure (MAP) was significantly improved in the CPR + canagliflozin group after ROSC compared with the CPR + placebo group (p < 0.05). Meanwhile, both ejection fraction (EF) and fraction shortening (FS) were dramatically increased in the CPR + canagliflozin group when compared with the CPR + placebo group at 2h, 4h, and 6h after ROSC (p < 0.05). In addition, the levels of NT-proBNP, cTn-I, and NLRP3 inflammatory inflammasome-associated proteins were significantly decreased in the CPR + canagliflozin group compared with the CPR + placebo group.

Conclusions: In type 2 diabetic rats, pretreatment of canagliflozin alleviates PRMD. The potential mechanisms may include inhibition of the NLRP3/caspase-1 signaling pathway.

Keywords: Canagliflozin; Cardiopulmonary resuscitation; Myocardial function; Post-resuscitation; Type 2 diabetes mellitus.