Reductions in mitochondrial O(2) consumption and preservation of high-energy phosphate levels after simulated ischemia in chronic hibernating myocardium.
We performed the present study to determine whether hibernating myocardium is chronically protected from ischemia. Myocardial tissue was rapidly excised from hibernating left anterior descending coronary regions (systolic wall thickening = 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 degrees C). At baseline, ATP (20.1 +/- 1.0 vs. 26.7 +/- 2.1 micromol/g dry wt, P < 0.05), ADP (8.1 +/- 0.4 vs. 10.3 +/- 0.8 micromol/g, P < 0.05), and total adenine nucleotides (31.2 +/- 1.3 vs. 40.1 +/- 2.9 micromol/g, P < 0.05) were depressed compared with normal myocardium, whereas total creatine, creatine phosphate, and ATP-to-ADP ratios were unchanged. During simulated ischemia, there was a marked attenuation of ATP depletion (5.6 +/- 0.9 vs. 13.7 +/- 1.7 micromol/g at 20 min in control, P < 0.05) and mitochondrial respiration [145 +/- 13 vs. 187 +/- 11 ng atoms O(2).mg protein(-1).min(-1) in control (state 3), P < 0.05], whereas 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.
Hu
Qingsong
Q
Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, NY 14214, USA.
Suzuki
Gen
G
Young
Rebeccah F
RF
Page
Brian J
BJ
Fallavollita
James A
JA
Canty
John M
JM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D003326:Coronary Circulation / Q000502:physiology; D054059:Coronary Occlusion / Q000503:physiopathology; D003331:Coronary Vessels / Q000503:physiopathology; D004594:Electrophysiology; D004699:Endocardium / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005456:Fluorescent Dyes; D019344:Lactic Acid / Q000378:metabolism; D008929:Mitochondria, Heart / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D017682:Myocardial Stunning / Q000378:metabolism* / Q000503:physiopathology; D010101:Oxygen Consumption / Q000502:physiology*; D010710:Phosphates / Q000378:metabolism*; D013552:Swine
D005456:Fluorescent Dyes; D010710:Phosphates; D019344:Lactic Acid; D000255:Adenosine Triphosphate