Abstract 13180: Trans-Valvular Unloading Reduces Anaerobic Glycolysis Before Reperfusion and Preserves Energy Substrate Utilization After Reperfusion in Models of Acute Myocardial Infarction

Abstract

Background: The impact of mechanical left ventricular (LV) unloading before reperfusion on myocardial energetics in acute myocardial infarction (AMI) is unknown. We hypothesized that LV unloading reduces anaerobic glycolysis in models of ischemia reperfusion injury (IRI). Methods: Myocardial ischemia was induced by percutaneous occlusion of the left anterior descending (LAD) artery for 90 minutes in adult swine. In Groups A and B, an additional 120 minutes of LAD occlusion without reperfusion was performed in the presence or absence of a trans-valvular pump (TVP). In Group C and D, an additional 120 minutes of reperfusion was performed in the presence or absence TVP (Fig. 1A). Untargeted Metabolomics was performed on the tissues from the infarct zones. Results: Compared to Group A, infarct size normalized to the area at risk (IS/AAR) was significantly smaller with LV unloading after ischemia alone (Group B; Fig 1B) and reperfusion (Group D; Fig 1B). Principal component analysis analysis of 800 metabolites identified 5 distinct clusters corresponding to the 4 study groups and sham controls (Fig 1C). LV unloading without reperfusion reduced lactate by 30±4% (p<0.006), glucose by 25±5% (p<0.02), and intermediates of glucose metabolism, Fructose 1,6-diphosphate by 9.3%, p<0.008) and ATP by 14±5% (p<0.04) consistent with decreased anaerobic glycolysis and reduced myocardial oxygen demand (Fig 1D Groups A and B). LV unloading followed by reperfusion increased lactate and glucose levels by 30±5% and 75±30% (p<0.05). Consistent with reduced glycolytic metabolites during ischemia with unloading, we observed significantly reduced levels of genes and proteins associated with glycolysis including mRNA expression of Glut1 and PDK1 within the infarct zone.We report for the first time that LV unloading during coronary occlusion reduces anaerobic glycolysis, energy substrate utilization and ATP production before reperfusion.