• Dwight D Harris, Mark Broadwin, Sharif A Sabe, Chris Stone, Meghamsh Kanuparthy, Ju-Woo Nho, Krishna Bellam, Debolina Banerjee, M Ruhul Abid, and Frank W Sellke.
• Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI.
• J. Thorac. Cardiovasc. Surg. 2024 Nov 1; 168 (5): e183e199e183-e199.

IntroductionSodium-glucose cotransporter-2 inhibitors are antidiabetic medications that have been shown to decrease cardiovascular events and heart failure-related mortality in clinical studies. We attempt to examine the complex interplay between metabolic syndrome and the sodium-glucose cotransporter-2 inhibitor canagliflozin (CAN) in a clinically relevant model of chronic myocardial ischemia.MethodsTwenty-one Yorkshire swine were fed a high-fat diet starting at 6 weeks of age to induce metabolic syndrome. At 11 weeks, all underwent placement of an ameroid constrictor around the left circumflex coronary artery to induce chronic myocardial ischemia. After 2 weeks, swine received either control (CON) (n = 11) or CAN 300 mg by mouth daily (n = 10) for 5 weeks, whereupon all underwent terminal harvest.ResultsThere was a significant increase in cardiac output and heart rate with a decrease in pulse pressure in the CAN group compared with CON (all P values < .05). The CAN group had a significant increase in capillary density (P = .02). There was no change in myocardial perfusion or arteriolar density. CAN induced a significant increase in markers of angiogenesis, including Phospho-endothelial nitric oxide synthase, Endothelial nitric oxide synthase, vascular endothelial growth factor receptor-1, heat shock protein 70, and extracellular signal-regulated kinases (all P values < .05), plausibly resulting in capillary angiogenesis.ConclusionsCAN treatment leads to a significant increase in capillary density and augmented cardiac function in a swine model of chronic myocardial ischemia in the setting of metabolic syndrome. This work further elucidates the mechanism of sodium-glucose cotransporter-2 inhibitors in patients with cardiac disease; however, more studies are needed to determine if this increase in capillary density plays a role in the improvements seen in clinical studies.Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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