phosphorus-radioisotopes and Heart-Failure

Topics: Arm; Energy Metabolism; Exercise; Exercise Test; Exercise Tolerance; Female; Heart Failure; Humans; Leg; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Oxygen Consumption; Phosphorus Radioisotopes

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.. 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).. 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.

Topics: Adenosine Triphosphate; Animals; Aortic Valve Stenosis; Binding, Competitive; Biomarkers; Biopsy; Blood Pressure; Chromium; Creatine Kinase; Disease Models, Animal; Energy Metabolism; Heart Failure; Heart Rate; Hypertrophy, Left Ventricular; Kinetics; Magnetic Resonance Imaging; Phosphates; Phosphorus Radioisotopes; Protein Isoforms; Regional Blood Flow; Swine; Ventricular Dysfunction, Left

It is still a matter of debate, whether decreased protein expression of SERCA 2a and phospholamban (PLB), or alterations in the phosphorylation state of PLB are responsible for the reduced SERCA 2a function in failing human myocardium. Thus, in membrane preparations from patients with terminal heart failure due to idiopathic dilated cardiomyopathy (NYHA IV. heart transplants) and control hearts (NF), SERCA 2a activity was measured with an NADH coupled assay with as well as without stimulation with protein kinase A (PKA). The protein expression of SERCA 2a, PLB and calsequestrin as well as the phosphorylation status of PLB (Back-phosphorylation technique: Serine-16-PLB specific antibody) were analysed using Western blotting technique and specific antibodies. In NF, the maximal activity (Vmax) and the Ca(2+)-sensitivity of SERCA 2a activity were significantly higher compared to NYHA IV. Protein expression of SERCA 2a, PLB and calsequestrin were unchanged, whereas both, the phosphorylation status of PLB as well as serine-16-PLB-phosphorylation, were significantly reduced in NYHA IV. After stimulation with PKA only the Ca(2+)-sensitivity, but not Vmax increased concentration-dependently. Therefore, in human myocardium, the Ca(2+)-sensitivity but not the Vmax of SERCA 2a is regulated by cAMP-dependent phosphorylation of phospholamban at position serine-16. Threonine-17-PLB-phosphorylation or direct phosphorylation of SERCA 2a may be candidates for regulation of maximal SERCA 2a activity in human myocardium.

Topics: Adult; Blotting, Western; Calcium; Calcium-Binding Proteins; Calcium-Transporting ATPases; Cyclic AMP-Dependent Protein Kinases; Densitometry; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Female; Heart Failure; Humans; Kinetics; Male; Middle Aged; Myocardium; Phosphorus Radioisotopes; Phosphorylation

Assessment of left ventricular metabolism and function is important in patients on maintenance dialysis because congestive heart failure occurs quite frequently and has a poor prognosis. The purpose of this study was to evaluate the changes of myocardial high energy metabolism in dialysis patients by using phosphorus-31 (31P) magnetic resonance (MR) spectroscopy.. Phosphorus-31 spectra were obtained from anteroseptal wall of the heart in six normal subjects (mean age, 24 +/- 1 years) and 14 dialysis patients (mean age, 52 +/- 11 years), using a 1.5-tesla clinical MR system. Four patients had previous history of heart failure. Echocardiography was performed in all patients to evaluate left ventricular (LV) hypertrophy and LV function.. The averaged ratio of phosphocreatine (PCr)/beta-adenosine triphosphate (beta-ATP) in dialysis patients (1.15 +/- 0.25 mean +/- standard deviation), was significantly lower than that in healthy subjects (1.63 +/- 0.21; P < 0.01). There was no significant difference in PCr/beta-ATP ratios between the non-LV hypertrophy group (1.21 +/- 0.24; n = 7) and the LV hypertrophy group (1.09 +/- 0.24; n = 7). The averaged PCr/beta-ATP ratio in four patients with history of heart failure (0.96 +/- 0.18) was significantly lower than that of the 10 patients without history of heart failure (1.22 +/- 0.23; P < 0.05).. These results indicate that patients on maintenance dialysis have decreased PCr/beta-ATP ratio and 31P MR spectroscopy can provide noninvasive assessment of altered high energy phosphate metabolism.

Topics: Adenosine Triphosphate; Adult; Aged; Female; Heart Failure; Heart Ventricles; Humans; Kidney Failure, Chronic; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myocardium; Phosphocreatine; Phosphorus; Phosphorus Radioisotopes; Renal Dialysis

Topics: Anticoagulants; Heart Failure; Humans; Phosphorus; Phosphorus Radioisotopes

Topics: Anticoagulants; Heart Failure; Heart Ventricles; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity