Organ-Specific Efficacy of Postischemic Empagliflozin in Acute Stroke and Myocardial Infarction Using Preclinical Models.

BACKGROUND

Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, has demonstrated cardioprotective and neuroprotective effects in preclinical myocardial infarction (MI) and ischemic stroke settings by reducing acute myocardial and cerebral infarction sizes. However, the optimal administration for acute protection remains unclear. Particularly, empagliflozin effects when administered after ischemia onset but before reperfusion have not been systematically evaluated for acute MI and stroke models.

METHODS

Sprague-Dawley rats underwent either middle cerebral artery occlusion/reperfusion to induce acute ischemic stroke (n=25), or left coronary artery occlusion/reperfusion to induce acute MI (n=29). Empagliflozin (20 mg/kg) or saline was administered 10 minutes after ischemia onset. Outcomes included brain/heart injury sizes and cardiac hemodynamics were quantified after 3 hours of reperfusion.

RESULTS

In the stroke model, postocclusion empagliflozin administration significantly reduced cerebral total infarct volume compared with controls (80.83±16.59 versus 164.10±26.23 mm3, P=0.014), corresponding to ≈50% reduction in the infarct volume percentage, while edema was unchanged. In the MI model, empagliflozin did not reduce myocardial infarct size, ischemic risk area, or no-reflow zone when given after occlusion/before reperfusion.

CONCLUSIONS

Our findings highlight that empagliflozin, when administered after ischemia onset but before reperfusion, provides robust neuroprotection in acute ischemic stroke but fails to limit myocardial injury in acute MI. The divergent outcomes may reflect organ-specific pathophysiology; for example, cerebral collaterals preserve residual perfusion and drug delivery, whereas limited cardiac collateralization leads to rapid necrosis and poor drug access. Clinically, these findings suggest that early postocclusion empagliflozin therapy may be beneficial in ischemic stroke, whereas comparable early administration appears insufficient in MI.