title: Selective versus nonselective beta-adrenergic receptor blockade in chronic heart failure: differential effects on myocardial energy substrate utilization.
abstract: BACKGROUND
  Non-selective and selective beta-blockers have been shown to improve outcomes in chronic heart failure (CHF). Recent data suggests the non-selective beta-blockers have a more favourable effect on outcomes than beta(1)-selective agents. We sought to examine the differential effects of non-selective versus selective beta-blockade on myocardial substrate utilization in patients with CHF.
  
  
  RESULTS
  Twenty-two patients with CHF were randomised to the non-selective beta-blocker carvedilol or the selective beta-blocker metoprolol (double-blind). Measurement of hemodynamics, arterial and coronary sinus free fatty acid (FFA) and lactate levels, and cardiac norepinephrine spillover (CANESP) were made before and after 4 months of therapy. In the carvedilol group (n=11), there was a significant reduction in myocardial FFA uptake (0.12+/-0.02 to 0.1+/-0.02 mmol/l, P<0.03). By contrast, in the metoprolol group (n=11) there was no change in myocardial FFA extraction. Carvedilol therapy tended to increase myocardial lactate extraction (0.24+/-0.05 to 0.35+/-0.08 mmol/l, P=0.08) while metoprolol therapy resulted in a trend in the opposite direction (0.18+/-0.03 to 0.11+/-0.04 mmol/l, P=0.09). The change in lactate extraction in the carvedilol group was significantly different from that in the metoprolol group (+0.11+/-0.06 vs. -0.09+/-0.04 mmol/l, P<0.01). Carvedilol treatment caused a significant reduction in CANESP while metoprolol had a neutral effect (-95+/-27 vs. 25+/-42 pmol/min, carvedilol vs. metoprolol P<0.03).
  
  
  CONCLUSIONS
  Carvedilol treatment caused a 20% reduction in myocardial free fatty acid extraction while metoprolol had a neutral effect. These differences are most probably related to the differential effects of these two agents on efferent cardiac sympathetic activity and may be relevant to the reported differential effects of these drugs on clinical outcomes.
authors.affiliation: Division of Cardiology, Department of Medicine, Mount Sinai Hospital and University Health Network Hospitals, University of Toronto, 600 University Avenue, Suite 1609, Toronto, Ontario, Canada, M5G 1X5.
authors.forename: Abdul
authors.initials: A
authors.lastname: Al-Hesayen
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Azevedo
authors.forename: John S
authors.initials: JS
authors.lastname: Floras
authors.forename: Shauna
authors.initials: S
authors.lastname: Hollingshead
authors.forename: Gary D
authors.initials: GD
authors.lastname: Lopaschuk
authors.forename: John D
authors.initials: JD
authors.lastname: Parker
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007773:Lactates / Q000378:metabolism; D008790:Metoprolol / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D013564:Sympathetic Nervous System / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol