Effects of Intracoronary SuperSaturated Oxygen Therapy on Myocardial Blood Flow, Microvascular Obstruction, and Myocardial Salvage in ST-Segment-Elevation Myocardial Infarction in Swine Ischemia/Reperfusion Model.

Abstract

Background: Early reperfusion after ST-segment-elevation myocardial infarction is essential for limiting infarct size. However, reperfusion injury can lead to progressive microvascular obstruction (MVO), reducing myocardial blood flow (MBF), aggravating ischemia and myocardial necrosis. We hypothesized that SuperSaturated Oxygen (SSO₂) Therapy may reduce infarct size by alleviating MVO, so we evaluated the effects of SSO₂ on the time course of MBF and MVO in a preclinical ischemia/reperfusion model.

Methods: Twelve swine surviving 90 minutes of balloon-induced anterior ST-segment-elevation myocardial infarction and 15-minute auto-reperfusion, were assigned to 120 minutes of SSO₂ (n=6) or further 120 minutes of auto-reperfusion (control, n=6). Microspheres were injected into the left ventricle at multiple time points to assess MBF, calculated as the total blood flow within areas at risk normalized to the total flow within remote zones. An angiography-derived index of microcirculatory resistance was analyzed. MVO and infarct zones were identified using thioflavin-S and 2,3,5-triphenyl tetrazolium chloride staining and quantified with ImageJ software.

Results: SSO₂ Therapy significantly reduced MVO compared with controls (4.64% versus 13.00% of left ventricular area; P<0.001) and improved myocardial salvage index (MSI, 64.76% versus 43.11%; P=0.03). MBF was significantly higher in the SSO₂ group compared with controls at the end of therapy (1.1 versus 0.59; P=0.03). In the controls, following initial hyperemia, flow decreased significantly at 165, 195, and 225 minutes (P=0.01). Conversely, the SSO₂ group showed no significant decrease in MBF in the same interval (P=0.38). Median angiography-derived index of microcirculatory resistance values showed a nonsignificant trend of reduced final microvascular resistance in the SSO₂ group only.

Conclusions: In a translational ST-segment-elevation myocardial infarction model, SSO₂ prevented a reduction in MBF during the 120-minute reperfusion period, with significantly increased MBF at the end of the experiment. MBF improvement was translated to a 64% relative reduction in the extent of MVO, and a 50% relative increase in the myocardial salvage index.