Effects of intracoronary supersaturated oxygen infusion on the time course of myocardial blood flow and extent of microvascular obstruction in an ischemia/reperfusion preclinical swine model
Authors: Melo P , Kachel M , Nowak K , Cheng Y , Wilburn P , Blum D , Perumal R , Creech J , Kloner R , Granada J F , Kaluza G L , Burkhoff D 
Published: October 2024

Abstract

Introduction
Despite successful epicardial reperfusion with primary PCI, reactive changes in microvascular function lead to impaired myocardial reperfusion. Intracoronary SuperSaturated Oxygen Therapy (SSO2) is the only approved therapy that improves myocardial salvage in STEMI pts through the delivery of hyperbaric levels of oxygen to viable ischemic vascular and myocardial cells. Several important questions remain unanswered regarding the potential mechanisms of this benefit. Therefore, the purpose of this study is to determine the effects of SSO2 on the time course of myocardial blood flow (MBF) and the extent of microvascular obstruction (MVO) in an ischemia/reperfusion model.

Methods
10 swine (32-40 kg) surviving 90-minute balloon-induced anterior STEMI, and 15-min auto reperfusion, were assigned to 120-min of SSO2 (n=5) or control (n=5) with 120-min auto reperfusion. MBF was evaluated at various time points during the experiment by injection of 15–µm microspheres (BioPal, USA) through a catheter placed in the left ventricle. Before euthanasia, 4% thioflavin-S (TS) was injected into the left anterior descending artery. The left ventricle was sectioned into 10-mm thick slices, and the myocardial rings were photographed under UV light to determine areas at risk (TS positive), MVO (lack of TS staining within TS positive area), and remote zones (contiguous areas unstained by TS). MBF was calculated as the total blood flow within the areas at risk normalized to the total flow within the remote zones.

Results
All animals experienced significant reduction (p = 0.02) in MBF due to balloon occlusion at the 85-minute MI timepoint compared to baseline (Fig). Following the removal of occlusion, reactive hyperemic flows were observed for both groups at the 15-minute auto reperfusion time point (Fig). Starting at the 30-min time point of autoperfusion to 120-min, the MBF significantly decreased (p=0.02) in the controls (Fig). In contrast during these time points, for the SSO2 group the MBF values were numerically higher than the controls, with average MBF for the SSO2 group being significantly higher (p = 0.03) than the controls (1.1 ± 0.18 vs 0.6 ± 0.13, respectively) at the 120-min timepoint (Fig). MVO was found within the areas at risk in all animals, but the extent of MVO in relation to the area at risk was significantly reduced (p &lt; 0.001) in the SSO2 group versus controls (15.2 ± 7.3% vs 41.8% ± 6.2%, respectively).

Conclusions
Results from this study showed that in a STEMI swine model, SSO2 prevented reduction in MBF during the 120-min reperfusion period, with significantly increased MBF at the end of the experiment compared to controls. This flow improvement translated to a 64% relative reduction in the extent of MVO compared to controls. These results suggest that one of the mechanisms by which SSO2 improves myocardial salvage may be by limiting early microcirculatory alterations set in motion by a cascade of reduced myocardial flow and MVO.Myocardial Blood Flow vs Time