Objective This experimental study investigates the potential of sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin to enhance cardiac hemodynamic and metabolism function following ischemia/reperfusion (I/R) after cold cardioplegic arrest. Methods Hearts of adult male C57BL/6 J mice were excised and mounted on an isolated working heart system. Cold ischemia (100 min) was induced using St. Thomas’ #2 cardioplegia, applied every 20 min, followed by 30 min of reperfusion. Continuous monitoring of cardiac parameters was performed. The experimental groups were the following (1) cold cardioplegic arrest as control (n = 12), (2) dapagliflozin applied to perfusion buffer 30 min prior to ischemia (n = 16), (3) arrested hearts receiving dapagliflozin as an adjunct to cardioplegia (n = 13), and (4) no-arrested, no-treated hearts (n = 6). Post-protocol, biopsies of hearts were frozen for subsequent metabolic and RT-qPCR analysis. Additionally, cell culture experiments on HUVECS and cardiac myoblasts were performed. Results Cold I/R markedly reduced systolic and diastolic function. Notably, dapagliflozin administered before ischemia significantly improved left ventricular recovery by enhancing contractility, aortic flow, and left ventricle diastolic function, whereas adding dapagliflozin only to the cardioplegic solution did not yield similar effects. High-energy phosphate (HEP) measurements revealed a statistically significant increase of myocardial energy charge in hearts treated with dapagliflozin via cardioplegia. These functional and metabolic findings were supported by improved cell viability and higher HEP content in HUVECS and cardiac myoblasts, when pre-treated with SGLT2i. Discussion Our findings underscore the potential of SGLT2i to improve hemodynamic recovery following cardioplegic arrest, supporting further exploration of dapagliflozin as novel myocardial protective regimen in cardiac surgery.
Dapagliflozin enhances hemodynamic and metabolic recovery following cardioplegic arrest in the isolated working mouse heart
Godel M.;Guerra G.;Ghigo A.;Riganti C.;
2025-01-01
Abstract
Objective This experimental study investigates the potential of sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin to enhance cardiac hemodynamic and metabolism function following ischemia/reperfusion (I/R) after cold cardioplegic arrest. Methods Hearts of adult male C57BL/6 J mice were excised and mounted on an isolated working heart system. Cold ischemia (100 min) was induced using St. Thomas’ #2 cardioplegia, applied every 20 min, followed by 30 min of reperfusion. Continuous monitoring of cardiac parameters was performed. The experimental groups were the following (1) cold cardioplegic arrest as control (n = 12), (2) dapagliflozin applied to perfusion buffer 30 min prior to ischemia (n = 16), (3) arrested hearts receiving dapagliflozin as an adjunct to cardioplegia (n = 13), and (4) no-arrested, no-treated hearts (n = 6). Post-protocol, biopsies of hearts were frozen for subsequent metabolic and RT-qPCR analysis. Additionally, cell culture experiments on HUVECS and cardiac myoblasts were performed. Results Cold I/R markedly reduced systolic and diastolic function. Notably, dapagliflozin administered before ischemia significantly improved left ventricular recovery by enhancing contractility, aortic flow, and left ventricle diastolic function, whereas adding dapagliflozin only to the cardioplegic solution did not yield similar effects. High-energy phosphate (HEP) measurements revealed a statistically significant increase of myocardial energy charge in hearts treated with dapagliflozin via cardioplegia. These functional and metabolic findings were supported by improved cell viability and higher HEP content in HUVECS and cardiac myoblasts, when pre-treated with SGLT2i. Discussion Our findings underscore the potential of SGLT2i to improve hemodynamic recovery following cardioplegic arrest, supporting further exploration of dapagliflozin as novel myocardial protective regimen in cardiac surgery.
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