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Myocardial Infarction and Functional Outcome Assessment in Pigs
Published on: April 25, 2014
SGLT2 Inhibitor, Canagliflozin, Attenuates Myocardial Infarction in the Diabetic and Nondiabetic Heart
Ven G Lim1, Robert M Bell1, Sapna Arjun1
1The Hatter Cardiovascular Institute, University College London, London, United Kingdom.
Abstract:
The authors hypothesized that despite similar cardiovascular event rates, the improved cardiovascular survival from sodium glucose transporter 2 (SGLT2) inhibition, seen clinically, could be via a direct cytoprotective effect, including protection against myocardial ischemia/reperfusion injury. Langendorff-perfused hearts, from diabetic and nondiabetic rats, fed long-term for 4 weeks with canagliflozin, had lower infarct sizes; this being the first demonstration of canagliflozin's cardioprotective effect against ischemia/reperfusion injury in both diabetic and nondiabetic animals. By contrast, direct treatment of isolated nondiabetic rat hearts with canagliflozin, solubilized in the isolated Langendorff perfusion buffer, had no impact on infarct size. This latter study demonstrates that the infarct-sparing effect of long-term treatment with canagliflozin results from either a glucose-independent effect or up-regulation of cardiac prosurvival pathways. These results further suggest that SGLT2 inhibitors could be repurposed as novel cardioprotective interventions in high-risk cardiovascular patients irrespective of diabetic status.
Insights
Sodium glucose transporter 2 (SGLT2) inhibitors like canagliflozin offer direct heart protection against injury, regardless of diabetes status. Long-term use reduces heart damage, suggesting new cardiovascular treatment possibilities.
Area of Science:
- Cardiology
- Pharmacology
- Molecular Biology
Background:
- Sodium glucose transporter 2 (SGLT2) inhibitors improve cardiovascular survival, but the mechanism remains unclear.
- A potential mechanism is direct cytoprotection, specifically against myocardial ischemia/reperfusion (I/R) injury.
Purpose of the Study:
- To investigate the direct cardioprotective effects of SGLT2 inhibition against myocardial I/R injury.
- To determine if canagliflozin's cardioprotective effects are glucose-dependent or independent.
Main Methods:
- Langendorff-perfused hearts from diabetic and nondiabetic rats were used.
- Hearts were pre-treated long-term (4 weeks) with canagliflozin or acutely with canagliflozin.
- Infarct size was measured following I/R injury.
Main Results:
- Long-term canagliflozin treatment significantly reduced infarct size in both diabetic and nondiabetic rat hearts.
- Acute treatment with canagliflozin did not affect infarct size in isolated hearts.
- These findings suggest a glucose-independent or pathway-mediated protective effect.
Conclusions:
- Long-term SGLT2 inhibition with canagliflozin confers cardioprotection against I/R injury.
- The cardioprotective effect appears to be independent of glucose levels, possibly via prosurvival pathways.
- SGLT2 inhibitors may be repurposed for cardiovascular protection in high-risk patients, irrespective of diabetes.
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