ISSN 2996-8215
International Journal of Cardiology | Vol. 4, No. 1, January 2013 | pp. 1–8
DOI: 10.46882/2013/IJC/000046
Original Research Article
Cardioprotective Effects of Empagliflozin in a Rat Model of Ischemic Heart Failure: Modulation of Myocardial Energetics
Heinrich Scholz¹, Klaus Richter¹, Manfred Ziegler²
¹Department of Cardiovascular Pharmacology, University Heart Center Freiburg, Freiburg, Germany
²Division of Experimental Cardiology, Max Delbrück Center for Molecular Medicine, Berlin, Germany
Abstract:
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce heart failure hospitalizations in clinical trials, but their exact cardiac mechanism of action remains poorly defined since SGLT2 is not directly expressed in the myocardium. This study investigated the direct cardioprotective effects of empagliflozin on myocardial function and tissue energetics in a non-diabetic rat model of chronic ischemic heart failure. Heart failure was induced in adult male Wistar rats via permanent ligation of the left anterior descending coronary artery. Two weeks post-ligation, surviving rats were randomized to receive either empagliflozin (20 mg/kg/day, n = 15) or vehicle control (n = 15) via oral gavage for 6 weeks. Cardiac function was tracked using high-resolution echocardiography, and myocardial high-energy phosphate metabolites were quantified post-sacrifice using nuclear magnetic resonance spectroscopy. Treatment with empagliflozin significantly attenuated left ventricular dilation and preserved LVEF compared with the vehicle control group (38.6% ± 3.4% vs. 31.2% ± 2.9%, p < 0.01). Mechanistically, empagliflozin-treated rats demonstrated a significant increase in the myocardial phosphocreatine-to-adenosine triphosphate (PCr/ATP) ratio (1.85 ± 0.14 vs. 1.42 ± 0.11, p < 0.01), indicating enhanced mitochondrial energetic efficiency. Myocardial glucose utilization was reduced, while beta-hydroxybutyrate oxidation was up-regulated, confirming a shift toward ketone body utilization. Empagliflozin significantly preserves left ventricular systolic function and attenuates adverse remodeling in non-diabetic ischemic heart failure rats by optimizing myocardial fuel selection and enhancing high-energy phosphate availability.
Keywords: Heart failure, SGLT2 inhibitors, Empagliflozin, Myocardial energetics, Remodeling, Animal model
Received: October 05, 2012; Revised: November 18, 2012; Accepted: December 08, 2012; Published: January 15, 2013
Citation: International Journal of Cardiology, 2013, Vol. 4, No. 1, pp. 1–8, DOI: 10.46882/2013/IJC/000046