title: The link between acute haemodynamic adrenergic beta-blockade and long-term effects in patients with heart failure. A study on diastolic function, heart rate and myocardial metabolism following intravenous metoprolol.
abstract: The present study was performed to find possible mechanisms linking the early effects of beta-blockade with the observed long-term effects in patients with heart failure. In 57 patients with heart failure, 13 +/- 3.1 mg of metoprolol was given intravenously. The patients were investigated by invasive haemodynamics (n = 34), including collection of myocardial metabolic data during atrial pacing stress (n = 16), by radionuclide angiography during physiological atrial pacing (n = 13), and by a bedside evaluation (n = 10). Diastolic function, measured by early peak filling rate, followed changes in heart rate, but was similar when heart rate was held constant by atrial pacing before and after beta-blockade. Following beta-blockade and slower heart rates, diastolic filling volumes were redistributed to late diastole. Metoprolol induced a parallel decrease in coronary sinus flow and myocardial oxygen consumption. Myocardial oxygen consumption following beta-blockade decreased both during spontaneous rhythm (25 +/- 15 to 16 +/- 8.8 ml min-1; P = 0.006), and during atrial pacing stress (30 +/- 13 to 23 +/- 11 ml.min-1; P = 0.004). Cardiac index decreased owing to reduction of heart rate (2.3 +/- 1.0 to 1.9 +/- 0.64 l.min-1.m2; P = 0.0003), while left ventricular filling pressure was unchanged. Ejection fraction and ventricular volumes were unaltered following atrial pacing or beta-blockade. There was a reflex increase in noradrenaline concentration after beta-blockade injection (0.96 +/- 0.66 to 1.20 +/- 0.91 nmol.l-1; P = 0.002), whereas myocardial noradrenaline overflow was unchanged. There was a trend towards an increase in myocardial lactate consumption after beta-blockade administration during atrial pacing stress. It is suggested that the surprisingly good tolerability seen after acute administration of beta-blockers to patients with severe heart failure may be explained by prolongation of the diastolic filling phase, which outweighs the negative inotropic effects. The reduced myocardial metabolic demand may allow the failing myocardium to recover and explain the excellent long-term effect on heart function following beta-blockade treatment.
authors.affiliation: Wallenberg Laboratory for Cardiovascular Research, Salgrenska Sjukhuset, University of Göteborg, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Andersson
authors.forename: M
authors.initials: M
authors.lastname: Lomsky
authors.forename: F
authors.initials: F
authors.lastname: Waagstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002304:Cardiac Pacing, Artificial; D009202:Cardiomyopathies / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D003971:Diastole / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D015637:Gated Blood-Pool Imaging / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008790:Metoprolol / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D011943:Receptors, Adrenergic, beta; D008790:Metoprolol