Semaglutide Improves Myocardial Perfusion and Performance in a Large Animal Model of Coronary Artery Disease.
Publication/Presentation Date
8-16-2024
Abstract
OBJECTIVE: Coronary artery disease (CAD) is the leading cause of death worldwide. It imposes an enormous symptomatic burden on patients, leaving many with residual disease despite optimal procedural therapy, and up to 1/3 with debilitating angina amenable neither to procedures, nor to current pharmacologic options. Semaglutide, a glucagon-like peptide 1 agonist originally approved for management of diabetes, has garnered substantial attention for its capacity to attenuate cardiovascular risk. Although subgroup analyses in patients indicate promise, studies explicitly designed to isolate the impact of semaglutide on the sequelae of CAD, independently of comorbid diabetes or obesity, are lacking.
APPROACH AND RESULTS: Yorkshire swine (n=17) underwent placement of an ameroid constrictor around the left circumflex coronary artery to induce CAD. Oral semaglutide was initiated postoperatively at 1.5 mg and scaled up in 2 weeks to 3 mg in treatment animals (SEM, n=8) for a total of 5 weeks, while control animals (CON, n=9) received no drug. All then underwent myocardial harvest with acquisition of perfusion and functional data using microsphere injection and pressure-volume loop catheterization. Immunoblotting, immunohistochemistry, and immunofluorescence were performed on the most ischemic myocardial segments for mechanistic elucidation. SEM animals exhibited improved left ventricular ejection fraction, both at rest and during rapid myocardial pacing (both p
CONCLUSION: This study is the first to reveal the capacity of oral semaglutide to augment cardiac function in the chronically ischemic heart in a highly translational large animal model, likely through AMPK-mediated improvement in endothelial function and perfusion to the ischemic myocardium.
ISSN
2692-8205
Published In/Presented At
Stone, C. R., Harris, D. D., Broadwin, M., Kanuparthy, M., Nho, J. W., Yalamanchili, K., Hamze, J., Abid, M. R., & Sellke, F. W. (2024). Semaglutide Improves Myocardial Perfusion and Performance in a Large Animal Model of Coronary Artery Disease. bioRxiv : the preprint server for biology, 2024.08.15.608191. https://doi.org/10.1101/2024.08.15.608191
Disciplines
Medicine and Health Sciences
PubMedID
39211263
Department(s)
Department of Surgery, Fellows and Residents
Document Type
Article