Intramyocardial injection of hypoxia-conditioned extracellular vesicles increases myocardial perfusion in a swine model of chronic coronary disease.
Publication/Presentation Date
8-1-2024
Abstract
OBJECTIVE: Coronary artery disease remains a leading cause of morbidity and mortality worldwide. Patients with advanced coronary artery disease who are not eligible for endovascular or surgical revascularization have limited options. Extracellular vesicles have shown potential to improve myocardial function in preclinical models. Extracellular vesicles can be conditioned to modify their components. Hypoxia-conditioned extracellular vesicles have demonstrated the ability to reduce infarct size and apoptosis in small animals. Our objective is to assess the potential benefits of hypoxia-conditioned extracellular vesicles in a large animal model of coronary artery disease.
METHODS: Coronary artery disease was induced in 14 Yorkshire swine by ameroid constriction of the left circumflex coronary artery. Two weeks postsurgery, swine underwent a repeat left thoracotomy for injections of hypoxia-conditioned extracellular vesicles (n = 7) or saline (control, n = 7). Five weeks later, all animals underwent terminal harvest for perfusion measurements and myocardial sectioning.
RESULTS: Myocardial perfusion analysis demonstrated a trend toward increase at rest and a significant increase during rapid pacing (
CONCLUSIONS: Intramyocardial injection of hypoxia-conditioned extracellular vesicles results in increased myocardial perfusion without a corresponding change in vessel density. Therefore, this improvement in perfusion is possibly due to changes in nitric oxide signaling. Hypoxia-conditioned extracellular vesicles represent a potential therapeutic strategy to increase myocardial perfusion in patients with advanced coronary artery disease.
Volume
20
First Page
49
Last Page
63
ISSN
2666-2736
Published In/Presented At
Harris, D. D., Sabe, S. A., Broadwin, M., Stone, C., Xu, C., Kanuparthy, M., Malhotra, A., Abid, M. R., & Sellke, F. W. (2024). Intramyocardial injection of hypoxia-conditioned extracellular vesicles increases myocardial perfusion in a swine model of chronic coronary disease. JTCVS open, 20, 49–63. https://doi.org/10.1016/j.xjon.2024.06.003
Disciplines
Medicine and Health Sciences
PubMedID
39296447
Department(s)
Department of Surgery, Fellows and Residents
Document Type
Article