High-energy phosphate metabolism and creatine kinase in failing hearts: a new porcine model.
BACKGROUND
This study aimed to create a pig model of heart failure secondary to severe aortic stenosis and to examine the relationship between the alterations in myocardial high-energy phosphate (HEP) metabolism and protein expression of creatine kinase (CK) isoforms.


RESULTS
Sixteen pigs with left ventricular hypertrophy (LVH) secondary to ascending aortic banding and 10 normal pigs (N) were studied. Myocardial protein levels of CK isoforms (Western blot), HEP levels, and CK kinetics ((31)P MR spectroscopy) were measured under basal conditions. Nine of the 16 animals with LVH developed congestive heart failure (CHF), as evidenced by ascites (100 to 2000 mL). LV weight/body weight ratio (g/kg) was 2.18+/-0.15 in N hearts, 3.04+/-0.14 in hearts with LVH (P<0.01), and 4.23+/-0.36 in hearts with CHF (P<0.01 versus LVH). Right ventricle weight/body weight ratio and LV end-diastolic pressure were significantly higher in hearts with CHF (each P<0.01 versus N or LVH). Myocardial phosphocreatine/ATP ratios and the CK forward flux rates were decreased in LVH hearts, most severely in hearts with CHF. CK-M/beta-actin ratios were 2.21+/-12 (N), 1.69+/-0.15 (LVH), and 1.39+/-0.27 (CHF, P<0.05 versus N). CK-mitochondria (CK-Mt)/beta-actin ratios were 1.40+/-0.09 (N), 1.24+/-0.09 (LVH), and 1.02+/-0.08 (CHF, P<0.05 versus N or LVH). The severity of the reduction of CK flux rate was linearly related to the severity of the decrease of CK-Mt/beta-actin (r=0.68, P<0.01).


CONCLUSIONS
In this new model of heart failure/hypertrophy, the abnormal myocardial HEP metabolism is related to the decreased CK-Mt protein level, which in turn is related to the severity of the hypertrophy.
Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, USA.
Y
Y
Ye
G
G
Gong
K
K
Ochiai
J
J
Liu
J
J
Zhang
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001024:Aortic Valve Stenosis / Q000150:complications; D001667:Binding, Competitive; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D001794:Blood Pressure; D002857:Chromium / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism*; D004195:Disease Models, Animal; D004734:Energy Metabolism; D006333:Heart Failure / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D006339:Heart Rate; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D010710:Phosphates / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D020033:Protein Isoforms / Q000378:metabolism; D012039:Regional Blood Flow; D013552:Swine; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
D015415:Biomarkers; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D020033:Protein Isoforms; D002857:Chromium; D000255:Adenosine Triphosphate; D003402:Creatine Kinase