What question did this study set out to answer?

The aim is to evaluate the protective effects of canagliflozin on myocardial injury induced by isoproterenol in rat models.

January 10, 2026Scientific Reports0 citationsOpen Access

Canagliflozin restores electrical properties and suppresses structural damage in isoproterenol-induced myocardial injury models

Q: What does this research mean for the field?

Canagliflozin significantly suppresses electrophysiological prolongation and improves mitochondrial integrity in isoproterenol-induced myocardial injury models. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

LKLisa KitasatoKitasato University YMYusuke MurayamaDai Nippon Printing (Japan)NINaruya IshizueElectrophysiology

Key Result

Canagliflozin significantly suppressed electrophysiological prolongation and improved mitochondrial integrity in isoproterenol-induced myocardial injury models.

Key Points

The aim is to evaluate the protective effects of canagliflozin on myocardial injury induced by isoproterenol in rat models.
Used Sprague Dawley rat hearts and neonatal rat ventricular cardiomyocytes (NRVCMs).
Investigated electrical and structural remodeling induced by isoproterenol.
Assessed the effects of canagliflozin on electrophysiological parameters and mitochondrial function.
Evaluated the impact of PI3K/Akt pathway inhibition.
Canagliflozin suppressed the prolongation of electrophysiological parameters caused by isoproterenol.
It reduced oxidative stress and preserved mitochondrial function.
Canagliflozin improved mitochondrial integrity and decreased apoptosis in NRVCMs.
The improvement was linked to downregulation of SGLT1, NCX1, and NHE1 expression.

Structured PICO

Does canagliflozin improve electrical properties and suppress structural damage in an isoproterenol-induced myocardial injury model?

Population

38 8-week-old male Sprague-Dawley rats and neonatal rat ventricular cardiomyocytes (NRVCMs) in an isoproterenol (ISP)-induced myocardial injury model.

Intervention

Canagliflozin 10 mg/kg/day via gastric tube starting 7 days prior to injury and continuing until day 7 (total 14 days) in rats; Canagliflozin pretreatment in NRVCMs.

Comparator

Isoproterenol (10 mg/kg subcutaneous injection) alone, Sham (saline injection + oral buffer water), and Canagliflozin alone.

Outcome

Electrophysiological parameters (ventricular effective refractory period, monophasic action potential duration), oxidative stress (d-ROMs), ketone body levels, and structural remodeling (apoptosis, hypertrophy) at 1 day (Acute phase) and 7 days (Sub-Acute phase).surrogate

Canagliflozin exerts cardioprotective effects by modulating electrical remodeling, enhancing mitochondrial function, and regulating calcium transport in a rat model of myocardial injury.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Canagliflozin (Cana), a sodium-glucose cotransporter 2 (SGLT2) inhibitor with additional affinity for SGLT1, has demonstrated cardioprotective effects. However, its role in modulating ventricular electrophysiology and structural remodeling under stress conditions remains insufficiently characterized. We have previously reported electrical and structural remodeling in a rat model of isoproterenol (ISP)-induced myocardial injury. In this study, we investigated the protective effects of Cana and its underlying mechanism in an ISP-induced myocardial injury model using Sprague Dawley rat hearts and in neonatal rat ventricular cardiomyocytes (NRVCMs). Our data revealed that Cana significantly suppressed ISP-induced prolongation of electrophysiological parameters, reduced oxidative stress, preserved mitochondrial function, and elevated ketone body levels. In NRVCMs, Cana -rather than β-hydroxybutyrate (βOHB)- improved mitochondrial integrity, attenuated apoptosis, and downregulated SGLT1, sodium-calcium exchanger 1 (NCX1), and sodium-hydrogen exchanger 1 (NHE1) expression. These effects were at least partly abolished by phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) inhibition. Collectively, these findings suggest that Cana modulates electrical remodeling and exerts cardioprotective effects by enhancing mitochondrial function and regulating calcium transport. These results underscore the therapeutic potential of Cana in cardiovascular diseases.

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