title: Early reduction in plasma norepinephrine during beta-blocking therapy with metoprolol in chronic heart failure.
abstract: BACKGROUND
  The possible role exerted by modulation of sympathetic outflow in the clinical effects of beta-blockade in chronic heart failure was tested during short- and long-term treatment.
  
  
  RESULTS
  Oral metoprolol (30-150 mg/day) was added to conventional therapy in 14 patients with idiopathic dilated cardiomyopathy, left ventricular ejection fraction (LVEF) of <0.45, and New York Heart Association class II or III. Norepinephrine plasma levels, which are an index of sympathetic activation, decreased by 27.57 +/- 18.03% after 1 month (P < .005), but returned to pretreatment levels after 6 months. LVEF increased by 7.7 +/- 6.0 ejection fraction units after 6 months (P < .005 vs baseline and P < .05 vs 1 month). Long-term beta-blockade resulted in nonsignificant improvements in functional class, symptom score, and oxygen consumption at peak exercise. After 1 month, the reduction in plasma norepinephrine levels and the changes in LVEF were inversely correlated (P < .01). No other correlation emerged during short- or long-term treatment.
  
  
  CONCLUSIONS
  In conclusion, the reduction in plasma norepinephrine levels during short-term beta-blockade was not proportional to the clinical benefits and may have been attributed to the direct inhibition of sympathetic outflow. The early reduction in circulating norepinephrine levels may decrease cardiac performance through withdrawal of sympathetic support when the favorable effects of beta-blockade have not had time to occur. The role that sympathetic modulation may exert in the long-term clinical benefits of metoprolol deserves further investigation.
authors.affiliation: Department of Pharmacology, University of Padova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Santostasi
authors.forename: D
authors.initials: D
authors.lastname: Fraccarollo
authors.forename: P
authors.initials: P
authors.lastname: Dorigo
authors.forename: C
authors.initials: C
authors.lastname: Egloff
authors.forename: G
authors.initials: G
authors.lastname: Miraglia
authors.forename: P G
authors.initials: PG
authors.lastname: Marinato
authors.forename: C
authors.initials: C
authors.lastname: Villanova
authors.forename: G
authors.initials: G
authors.lastname: Fasoli
authors.forename: I
authors.initials: I
authors.lastname: Maragno
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D002908:Chronic Disease; D004452:Echocardiography; D005080:Exercise Test; D005260:Female; D006334:Heart Function Tests; D006801:Humans; D016014:Linear Models; D008297:Male; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*; D011446:Prospective Studies; D013318:Stroke Volume / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D008790:Metoprolol; D009638:Norepinephrine