Abstract
BackgroundA sodium-glucose co-transporter 2 (SGLT-2) inhibitor had favorable impact on the attenuation of hyperglycemia together with the severity of heart failure. However, the effects of acute dapagliflozin administration at the time of cardiac ischemia/reperfusion (I/R) injury are not established.MethodsThe effects of dapagliflozin on cardiac function were investigated by treating cardiac I/R injury at different time points. Cardiac I/R was instigated in forty-eight Wistar rats. These rats were then split into 4 interventional groups: control, dapagliflozin (SGLT2 inhibitor, 1 mg/kg) given pre-ischemia, at the time of ischemia and at the beginning of reperfusion. Left ventricular (LV) function and arrhythmia score were evaluated. The hearts were used to evaluate size of myocardial infarction, cardiomyocyte apoptosis, cardiac mitochondrial dynamics and function.ResultsDapagliflozin given pre-ischemia conferred the maximum level of cardioprotection quantified through the decrease in arrhythmia, attenuated infarct size, decreased cardiac apoptosis and improved cardiac mitochondrial function, biogenesis and dynamics, leading to LV function improvement during cardiac I/R injury. Dapagliflozin given during ischemia also showed cardioprotection, but at a lower level of efficacy.ConclusionsAcute dapagliflozin administration during cardiac I/R injury exerted cardioprotective effects by attenuating cardiac infarct size, increasing LV function and reducing arrhythmias. These benefits indicate its potential clinical usefulness.
Highlights
A sodium-glucose co-transporter 2 (SGLT-2) inhibitor had favorable impact on the attenuation of hyperglycemia together with the severity of heart failure
The EMPA-REG OUTCOME trial reported the cardiovascular benefits of empagliflozin, a SGLT-2 inhibitor, by significantly decreasing the incidence of hospitalization associated with heart failure, cardiovascular-cause death rate and all-cause death rate in diabetic patients with cardiovascular diseases [10]
After 7 days of acclimatization, male Wistar rats (n = 48, 250–300 g, 8 weeks old) underwent cardiac I/R protocols. These rats were subdivided into four groups to enable 4 different treatments (Fig. 1): (1) Pretreated group: dapagliflozin was administered 15 min before cardiac ischemia; (2) Ischemia group: dapagliflozin was administered 15 min into the cardiac ischemic period; (3) Reperfusion group: dapagliflozin was administered at the onset of reperfusion, and 4) Control group: normal saline solution was administered to the rats as a vehicle
Summary
A sodium-glucose co-transporter 2 (SGLT-2) inhibitor had favorable impact on the attenuation of hyperglycemia together with the severity of heart failure. The effects of acute dapagliflozin administration at the time of cardiac ischemia/reperfusion (I/R) injury are not established. The results from this trial found no significant differences in the rate of AMI between group receiving treatment and placebo [10], there was a possible link highlighted between SGLT-2 inhibitors and cardioprotective effects attenuating AMI severity as evidenced by animal studies [11, 12]. Despite its potential benefits on the heart, the cardioprotective effects of acute dapagliflozin administration at the time of cardiac I/R injury has never been investigated. We aimed to study the temporal effects of acute dapagliflozin administration on cardiac function given at 3 different times during cardiac I/R injury in rats. Our hypothesis was that acute dapagliflozin administration given after cardiac ischemia could attenuate cardiac dysfunction in rats with cardiac I/R injury
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