Mitochondrial ATPase and high-energy phosphates in failing hearts.
This study examined high-energy phosphates (HEP) and mitochondrial ATPase protein expression in hearts in which myocardial infarction resulted in either compensated left ventricular remodeling (LVR) or congestive heart failure (CHF). The response of HEP (measured via (31)P magnetic resonance spectroscopy) to a modest increase in the cardiac work state produced by dobutamine-dopamine infusion and pacing (if needed) was examined in 17 pigs after left circumflex coronary artery ligation (9 with LVR and 8 with CHF) and compared with 7 normal pigs. In hearts with LVR, the baseline phosphocreatine (PCr)-to-ATP ratio decreased, and calculated ADP increased; these changes were most severe in hearts with CHF. HEP levels did not change in normal or LVR hearts during dobutamine-dopamine infusion. However, in hearts with CHF, the PCr-to-ATP ratio decreased further, and free ADP increased. The mitochondrial protein levels of the F(0)F(1)-ATPase subunits were normal in hearts with compensated LVR. However, in failing hearts, the alpha-subunit decreased by 36%, the beta-subunit decreased by 16%, the oligomycin sensitivity-conferring protein subunit decreased by 40%, and the initiation factor 1 subunit decreased by 41%. Thus in failing hearts, reductions in mitochondrial F(0)F(1)-ATPase protein expression are associated with increased myocardial free ADP.
Liu
J
J
Department of Medicine, University of Minnesota Health Sciences, Minneapolis, Minnesota 55455, USA.
Wang
C
C
Murakami
Y
Y
Gong
G
G
Ishibashi
Y
Y
Prody
C
C
Ochiai
K
K
Bache
R J
RJ
Godinot
C
C
Zhang
J
J
D000244:Adenosine Diphosphate / Q000032:analysis / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004280:Dobutamine / Q000008:administration & dosage; D004298:Dopamine / Q000008:administration & dosage; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D009682:Magnetic Resonance Spectroscopy; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism; D009929:Organ Size; D010725:Phosphocreatine / Q000032:analysis / Q000378:metabolism*; D021122:Protein Subunits; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D013552:Swine; D020257:Ventricular Remodeling / Q000187:drug effects
D021122:Protein Subunits; D010725:Phosphocreatine; D004280:Dobutamine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D004298:Dopamine