Sodium-glucose co-transporter 2 inhibition with empagliflozin improves cardiac function in non-diabetic rats with left ventricular dysfunction after myocardial infarction.

Autor: Yurista SR; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Silljé HHW; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Oberdorf-Maass SU; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Schouten EM; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Pavez Giani MG; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Hillebrands JL; Department of Pathology and Medical Biology, Division of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., van Goor H; Department of Pathology and Medical Biology, Division of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., van Veldhuisen DJ; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., de Boer RA; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Westenbrink BD; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Jazyk: angličtina
Zdroj: European journal of heart failure [Eur J Heart Fail] 2019 Jul; Vol. 21 (7), pp. 862-873. Date of Electronic Publication: 2019 Apr 29.
DOI: 10.1002/ejhf.1473
Abstrakt: Aims: Sodium-glucose co-transporter 2 (SGLT2) inhibition reduces heart failure hospitalizations in patients with diabetes, irrespective of glycaemic control. We examined the effect of SGLT2 inhibition with empagliflozin (EMPA) on cardiac function in non-diabetic rats with left ventricular (LV) dysfunction after myocardial infarction (MI).
Methods and Results: Non-diabetic male Sprague-Dawley rats underwent permanent coronary artery ligation to induce MI, or sham surgery. Rats received chow containing EMPA that resulted in an average daily intake of 30 mg/kg/day or control chow, starting before surgery (EMPA-early) or 2 weeks after surgery (EMPA-late). Cardiac function was assessed using echocardiography and histological and molecular markers of cardiac remodelling and metabolism were assessed in the left ventricle. Renal function was assessed in metabolic cages. EMPA increased urine production by two-fold without affecting creatinine clearance and serum electrolytes. EMPA did not influence MI size, but LV ejection fraction (LVEF) was significantly higher in the EMPA-early and EMPA-late treated MI groups compared to the MI group treated with vehicle (LVEF 54%, 52% and 43%, respectively, all P < 0.05). EMPA also attenuated cardiomyocyte hypertrophy, diminished interstitial fibrosis and reduced myocardial oxidative stress. EMPA treatment reduced mitochondrial DNA damage and stimulated mitochondrial biogenesis, which was associated with the normalization of myocardial uptake and oxidation of glucose and fatty acids. EMPA increased circulating ketone levels as well as myocardial expression of the ketone body transporter and two critical ketogenic enzymes, indicating that myocardial utilization of ketone bodies was increased. Together these metabolic changes were associated with an increase in cardiac ATP production.
Conclusion: Empagliflozin favourably affects cardiac function and remodelling in non-diabetic rats with LV dysfunction after MI, associated with substantial improvements in cardiac metabolism and cardiac ATP production. Importantly, it did so without renal adverse effects. Our data suggest that EMPA might be of benefit in heart failure patients without diabetes.
(© 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
Databáze: MEDLINE
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