Central Illustration.

History of Microvascular Obstruction Research and Supersaturated Oxygen Evolution

Timeline of microvascular obstruction (MVO) research/understanding and supersaturated oxygen (SSO₂) therapy concept development, clinical study, and approval. (First panel, Studies on infarct size)(Top) Medical illustration depicting MVO post-STEMI. (Bottom) Electron microscopic view of swollen endothelial cell (arrow) post-infarct in porcine model (46). There were many failed clinical trials with a variety of treatments that attempted to further reduce infarct size above and beyond reperfusion therapy; (Second panel, SSO₂ Concept Introduced) SSO₂ concept drawing showing administration of this therapy in the catheterization laboratory; (Third panel, Preclinical Studies)(Top) Porcine transverse myocardial slices post- infarct in control pig (left) showing large infarct and in treated pig (right) showing minimal infarction (45). (Bottom) Preclinical studies showed several beneficial effects of SSO₂ therapy; (Fourth Panel, Clinical Studies) (Top) Summary of consistent infarct size reduction trials conducted by TherOx, Inc (40,50,55); (Bottom) one-year propensity-matched IC-HOT data demonstrating no death, no new onset heart failure (HF), and no HF hospitalizations with SSO₂ therapy; chart supplied by G.W. Stone from data in Chen et al (57); (Fifth Panel, FDA Approval, 2019). FDA = Food and Drug Administration; IC-HOT = Intracoronary Hyperoxemic Oxygen Therapy study; INFUSE-AMI = The INFUSE-Anterior Myocardial Infarction (AMI) study; RBC = red blood cell; STEMI = ST-segment elevation myocardial infarction.