Key result
Dapagliflozin significantly improved left ventricular ejection fraction (60.56% vs 40.07%) and reduced ventricular arrhythmias compared to isoproterenol alone in rats with induced cardiomyopathy.
Why the study?
Although SGLT2 inhibitors improve glycaemic control in type 2 diabetes, their effect and mechanisms in isoproterenol-induced cardiomyopathy remained to be investigated.
Does dapagliflozin improve cardiac function and reduce ventricular arrhythmias in rats with isoproterenol-induced cardiomyopathy?
Does dapagliflozin improve cardiac function and reduce ventricular arrhythmias in rats with isoproterenol-induced cardiomyopathy?
Absolute Event Rate: 60.56% vs 40.07%
p-value: p=<0.05
Dapagliflozin effectively improved myocardial remodeling, oxidative stress, and cardiac function, and decreased ventricular arrhythmias in a rat model of isoproterenol-induced cardiomyopathy.
Hypothesis-generating in isoproterenol cardiomyopathy models; leaves open translation to human ventricular function or arrhythmia prevention.
Background: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) has been reported to improve glycaemic control in patients with type 2 diabetes. The aim of this study was to investigate the effect of SGLT2i Dapagliflozin (Dapa) on cardiomyopathy induced by isoproterenol (ISO) and its potential mechanism. Methods: Fifty male Sprague Dawley rats were randomly assigned to Control (n = 10) and ISO (2.5 mg/kg/day)-treated groups (n = 40). After 2 weeks, 28 survived rats with obvious left ventricular dysfunction in ISO group were randomized into three groups for medication including ARNI (angiotensin receptor neprilysin inhibitor, 68 mg/kg/day, n = 9), Dapa (3 mg/kg/day, n = 9) and ISO (saline, n = 10) for 4 weeks. After that, electrical programmed stimulation (EPS) was performed in all groups for the evaluation of the susceptibility of ventricular arrhythmias (VAs). Echocardiography was used to evaluate cardiac function. Results: Echocardiography revealed significant left ventricular (LV) dysfunction in rats with ISO treatment for 2 weeks compared to the control group. Dapa administration for 4 weeks reduced the cumulative risk of death, myocardial fibrosis, plasma angiotensin II level and its functional receptor AT1R protein expression in the heart, and proinflammatory cytokines levels in the cardiac tissue of ISO-treated rats. It also improved cardiac function and inhibited oxidative stress when compared to the ISO group. These effects were similar to ARNI. However, Dapa showed a greater efficacy than ARNI in reducing left ventricular end-diastolic volume, lowing heart rate and VAs, and decreasing body weight and plasma glucose in ISO-treated rats. Conclusion: Dapa effectively improved the myocardial remodelling and oxidative stress like ARNI in ISO-induced cardiomyopathy in rats, but Dapa may be more effectively in decreasing VAs, and improving cardiac function when compared to ARNI. The mechanisms by which Dapa exerts protective effects on cardiomyopathy may be related to its antioxidant capacity and hypoglycemic action.
No takes yet. Share an insight, caveat, or question.
Wang et al. (2021) studied Isoproterenol-induced cardiomyopathy (n=50). Dapagliflozin vs. Isoproterenol (saline) and ARNI was evaluated on Left ventricular ejection fraction (EF%) at 6 weeks (p=<0.05). Dapagliflozin significantly improved left ventricular ejection fraction (60.56% vs 40.07%) and reduced ventricular arrhythmias compared to isoproterenol alone in rats with induced cardiomyopathy.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: