title: The effects of beta(1)-blockade on oxidative metabolism and the metabolic cost of ventricular work in patients with left ventricular dysfunction: A double-blind, placebo-controlled, positron-emission tomography study.
abstract: BACKGROUND
  The mechanism for the beneficial effect of beta-blocker therapy in patients with left ventricular (LV) dysfunction is unclear, but it may relate to an energy-sparing effect that results in improved cardiac efficiency. C-11 acetate kinetics, measured using positron-emission tomography (PET), are a proven noninvasive marker of oxidative metabolism and myocardial oxygen consumption (MVO(2)). This approach can be used to measure the work-metabolic index, which is a noninvasive estimate of cardiac efficiency.
  
  
  RESULTS
  The aim of this study was to determine the effect of metoprolol on oxidative metabolism and the work-metabolic index in patients with LV dysfunction. Forty patients (29 with ischemic and 11 with nonischemic heart disease; LV ejection fraction <40%) were randomized to receive metoprolol or placebo in a treatment protocol of titration plus 3 months of stable therapy. Seven patients were not included in analysis because of withdrawal from the study, incomplete follow-up, or nonanalyzable PET data. The rate of oxidative metabolism (k) was measured using C-11-acetate PET, and stoke volume index (SVI) was measured using echocardiography. The work-metabolic index was calculated as follows: (systolic blood pressure x SVI x heart rate)/k. No significant change in oxidative metabolism occurred with placebo (k=0.061+/-0.022 to 0.054+/-0.012 per minute). Metoprolol reduced oxidative metabolism (k=0.062+/-0. 024 to 0.045+/-0.015 per minute; P:=0.002). The work-metabolic index did not change with placebo (from 5.29+/-2.46 x 10(6) to 5.14+/-2. 06 x 10(6) mm Hg. mL/m(2)), but it increased with metoprolol (from 5. 31+/-2.15 x 10(6) to 7.08+/-2.36 x 10(6) mm Hg. mL/m(2); P:<0.001).
  
  
  CONCLUSIONS
  Selective beta-blocker therapy with metoprolol leads to a reduction in oxidative metabolism and an improvement in cardiac efficiency in patients with LV dysfunction. It is likely that this energy-sparing effect contributes to the clinical benefits observed with beta-blocker therapy in this patient population.
authors.affiliation: Cardiac PET Centre in the Division of Cardiology at the University of Ottawa Heart Institute, Ottawa, Canada. rbeanlands@ottawaheart.ca
authors.forename: R S
authors.initials: RS
authors.lastname: Beanlands
authors.forename: C
authors.initials: C
authors.lastname: Nahmias
authors.forename: E
authors.initials: E
authors.lastname: Gordon
authors.forename: G
authors.initials: G
authors.lastname: Coates
authors.forename: R
authors.initials: R
authors.lastname: deKemp
authors.forename: G
authors.initials: G
authors.lastname: Firnau
authors.forename: E
authors.initials: E
authors.lastname: Fallen
mesh_terms: D000085:Acetates / Q000493:pharmacokinetics; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002250:Carbon Radioisotopes; D009202:Cardiomyopathies / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D010084:Oxidation-Reduction; D011859:Radiography; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D014055:Tomography, Emission-Computed; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000085:Acetates; D000319:Adrenergic beta-Antagonists; D002250:Carbon Radioisotopes; D018342:Receptors, Adrenergic, beta-1; D008790:Metoprolol