Submitted on September 12, 2008
Revised on April 14, 2009
Accepted on April 14, 2009
Reductions in Mitochondrial Oxygen Consumption and Preservation of High Energy Phosphate Levels Following Simulated Ischemia in Chronic Hibernating Myocardium
Qingsong Hu1, Gen Suzuki, Rebeccah F. Young1, Brain J Page2, James A Fallavollita1, and John M. Canty, Jr.1*
1 SUNY at Buffalo
2 SUNY at Buffalao
* To whom correspondence should be addressed. E-mail: canty{at}buffalo.edu.
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 ± 12.6 vs. 187 ± 11.2 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.
