Sodium-Glucose Cotransporter-2 Inhibition Normalizes Metabolic Derangements in the Ischemic Myocardium.

Autor: Stone C; Division of Cardiothoracic Surgery, Department of Surgery, The Warren Alpert Medical School of Brown University, Providence, Rhode Island., Harris DD; Division of Cardiothoracic Surgery, Department of Surgery, The Warren Alpert Medical School of Brown University, Providence, Rhode Island., Broadwin M; Division of Cardiothoracic Surgery, Department of Surgery, The Warren Alpert Medical School of Brown University, Providence, Rhode Island., Sabe SA; Division of Cardiothoracic Surgery, Department of Surgery, The Warren Alpert Medical School of Brown University, Providence, Rhode Island., Bellam K; Division of Cardiothoracic Surgery, Department of Surgery, The Warren Alpert Medical School of Brown University, Providence, Rhode Island., Kanuparthy M; Division of Cardiothoracic Surgery, Department of Surgery, The Warren Alpert Medical School of Brown University, Providence, Rhode Island., Abid MR; Division of Cardiothoracic Surgery, Department of Surgery, The Warren Alpert Medical School of Brown University, Providence, Rhode Island., Sellke FW; Division of Cardiothoracic Surgery, Department of Surgery, The Warren Alpert Medical School of Brown University, Providence, Rhode Island. Electronic address: frank_sellke@brown.edu.
Jazyk: angličtina
Zdroj: The Journal of surgical research [J Surg Res] 2024 Nov; Vol. 303, pp. 600-612. Date of Electronic Publication: 2024 Oct 21.
DOI: 10.1016/j.jss.2024.09.065
Abstrakt: Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown efficacy in the context of heart failure but have not been well-studied in ischemic heart disease. We employed a large animal model of chronic coronary artery disease and metabolic syndrome (MS) to investigate the hemodynamic and metabolic consequences of SGLT2i administration.
Methods: Thirty-eight Yorkshire swine were divided into two groups, with half (n = 21) receiving a high fat diet to induce MS, and the other half fed a standard diet (n = 17). All animals underwent thoracotomy for ameroid constrictor placement over the left circumflex coronary artery. Treatment with SGLT2i was then initiated, generating four groups: regular diet placebo (CON, n = 9), regular diet canagliflozin (n = 8), high-fat control (n = 11), and high-fat canagliflozin (n = 10). After 5 wks, all animals underwent terminal myocardial harvest with pressure-volume loop acquisition, perfusion studies, and tissue resection for molecular analysis.
Results: SGLT2i improved multiple measures of myocardial performance, including a nearly 1.5-fold increase in both cardiac output and ejection fraction; these changes were associated with augmented capillary density and a twofold increase perfusion to the ischemic myocardium. These augmentations were blunted; however, in the presence of MS, and associated with modulated myocardial expression of multiple major metabolic enzymes.
Conclusions: SGLT2i significantly improved cardiac function in our large animal model of coronary artery disease, with metabolic modulation of the myocardial tissue serving as a candidate account of these changes. The blunting seen with MS underscores the dependence of clinical translatability on faithful representation of the biochemical environment of human disease.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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