title: Effect of beta-adrenergic blockade on myocardial function and energetics in congestive heart failure. Improvements in hemodynamic, contractile, and diastolic performance with bucindolol.
abstract: The hemodynamic effects of beta-adrenergic blockade with bucindolol, a nonselective beta-antagonist with mild vasodilatory properties, were studied in patients with congestive heart failure. Fifteen patients (New York Heart Association class I-IV) underwent cardiac catheterization before and after 3 months of oral therapy with bucindolol. The left ventricular ejection fraction increased from 0.23 +/- 0.12 to 0.29 +/- 0.14 (p = 0.007), and end-systolic elastance, a relatively load-independent determinant of contractility, increased from 0.60 +/- 0.40 to 1.11 +/- 0.45 mm Hg/ml (p = 0.0049). Both left ventricular stroke work index (34 +/- 13 to 47 +/- 19 g-m/m2, p = 0.0059) and minute work (5.5 +/- 2.2 to 7.0 +/- 2.6 kg-m/min, p = 0.0096) increased despite reductions in left ventricular end-diastolic pressure (19 +/- 8 to 15 +/- 5 mm Hg, p = 0.021). There was an upward shift in the peak + dP/dtmax-end-diastolic volume relation (p = 0.0005). These data demonstrate improvements in myocardial contractility after beta-adrenergic blockade with bucindolol. At a matched paced heart rate of 98 +/- 15 min-1, the time constant of left ventricular isovolumic relaxation was significantly reduced by bucindolol therapy (92 +/- 17 versus 73 +/- 11 msec, p = 0.0013), and the relation of the time constant to end-systolic pressure was shifted downward (p = 0.014) with therapy. The slope of the logarithm left ventricular end-diastolic pressure-end-diastolic volume relation was unchanged (p = 0.51) after bucindolol. These data suggest that chronic beta-adrenergic blockade with bucindolol improves diastolic relaxation but does not alter myocardial chamber stiffness. Myocardial oxygen extraction, consumption, and efficiency were unchanged despite improvement in contractile function and mechanical work. Thus, in patients with congestive heart failure, chronic beta-adrenergic blockade with bucindolol significantly improves myocardial contractility and minute work, yet it does not do so at the expense of myocardial oxygen consumption. Additionally, bucindolol improves myocardial relaxation but does not affect chamber stiffness.
authors.affiliation: Cardiac Catheterization Laboratory, Dallas Veterans Administration Hospital, TX.
authors.forename: E J
authors.initials: EJ
authors.lastname: Eichhorn
authors.forename: J B
authors.initials: JB
authors.lastname: Bedotto
authors.forename: C R
authors.initials: CR
authors.lastname: Malloy
authors.forename: B A
authors.initials: BA
authors.lastname: Hatfield
authors.forename: D
authors.initials: D
authors.lastname: Deitchman
authors.forename: M
authors.initials: M
authors.lastname: Brown
authors.forename: J E
authors.initials: JE
authors.lastname: Willard
authors.forename: P A
authors.initials: PA
authors.lastname: Grayburn
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D003326:Coronary Circulation / Q000187:drug effects; D003971:Diastole; D004734:Energy Metabolism / Q000187:drug effects; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000627:therapeutic use*
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C024307:bucindolol