Effects of dapagliflozin on myoglobin efflux from cardiomyocyte during myocardial ischemia/reperfusion in anesthetized rats

Tomohiro Hayashida ^1,2, Yosuke Kuroko ³, Shuji Shimizu ^4,5

⁰Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.

Scientific Reports +

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July 16, 2024

View abstract on PubMed

Summary

Sodium-glucose cotransporter 2 (SGLT2) inhibitors like dapagliflozin show cardioprotective effects. Systemic administration before ischemia reduced heart muscle damage during reperfusion, independent of blood sugar levels.

Area Of Science

Cardiology
Pharmacology
Biochemistry

Background

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are known for potential cardioprotective effects beyond glucose reduction.
The impact of SGLT2 inhibitors on cardiomyocyte structural damage during ischemia/reperfusion (I/R) is not fully understood.

Purpose Of The Study

To investigate the effects of the SGLT2 inhibitor dapagliflozin on myocardial interstitial myoglobin levels.
To assess the cardioprotective potential of dapagliflozin against structural damage in the ischemic region during I/R.

Main Methods

Utilized a microdialysis technique in anesthetized rats to measure myoglobin levels in the ischemic region.
Administered dapagliflozin systemically (intravenous) or locally (via dialysis probe) before inducing coronary occlusion and reperfusion.

Main Results

Coronary occlusion and subsequent reperfusion significantly increased myoglobin levels in the ischemic region.
Systemic dapagliflozin administration reduced myoglobin levels during ischemia and early reperfusion.
Local administration of dapagliflozin did not show a significant effect on myoglobin levels.

Conclusions

Acute systemic administration of dapagliflozin prior to ischemia confers cardioprotective effects against structural damage during I/R.
The cardioprotective mechanism appears to be related to systemic action rather than local effects in the ischemic myocardium.

Keywords:

Cardiac microdialysis Dapagliflozin Myocardial ischemia/reperfusion Myoglobin Sodium-glucose-cotransporter 2 inhibitor