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

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.