1 Reductions in Mitochondrial Oxygen Consumption and Preservation of High Energy Phosphate Levels Following Simulated Ischemia in Chronic

We performed the present study to determine whether hibernating myocardium is chronically protected from ischemia. Myocardial tissue was rapidly excised from hibernating LAD regions (∆WT 2.8±0.2 vs. 5.4±0.3 mm in remote myocardium) and high-energy phosphates were quantified by HPLC during simulated ischemia in vitro (37°C). At baseline, ATP (20.1±1.0 vs. 26.7±2.1 μmol/g dry weight, p<0.05), ADP (8.1±0.4 vs. 10.3±0.8 μmol/g, p<0.05) and total adenine nucleotides (31.2±1.3 vs. 40.1±2.9 μmol/g, p<0.05) were depressed vs. normal myocardium while total creatine, CP and ATP/ADP ratios were unchanged. During simulated ischemia, there was a marked attenuation of ATP depletion (5.6±0.9 vs. 13.7±1.7 μmol/g at 20-minutes in control, p<0.05) and mitochondrial respiration (State 3 145±13 vs. 187±11 ng atoms O2/mg protein/min, p< 0.05) while lactate accumulation was unaffected. These in vitro changes were accompanied by protection of the hibernating heart from acute stunning during demand-induced ischemia. Thus, despite contractile dysfunction at rest, hibernating myocardium is ischemia tolerant with reduced mitochondrial respiration and slowing of ATP depletion during simulated ischemia which may maintain myocyte viability. Key words- energy metabolism; mitochondrial respiration; stunned myocardium; hibernatin