Loss of adrenergic control of the force-frequency relation in heart failure secondary to idiopathic or ischemic cardiomyopathy

Am J Cardiol. 1998 May 1;81(9):1130-7. doi: 10.1016/s0002-9149(98)00133-7.


This study was designed to determine whether the force-frequency effect on myocardial contractility, known to be importantly regulated by the adrenergic nervous system in experimental animals, can be enhanced by beta-adrenergic receptor stimulation in patients with heart failure. Animal experiments have demonstrated that the positive force-frequency relation in most mammals is subject to enhancement by beta-adrenergic receptor stimulation during exercise or infusion of a beta-receptor agonist. In animal models of heart failure, this regulatory mechanism generally is lost. The response to progressive increases in heart rate to 150 to 160 beats/min by right atrial pacing before and during dobutamine infusion was studied in 3 relatively normal subjects and in 5 patients with severe dilated cardiomyopathy. Left ventricular (LV) pressure and its first derivative (LV dP/dt(max)) were measured with a micromanometer, and the time constant of LV relaxation was assessed. The slopes of the relations between heart rate and LV dP/dt(max) in control subjects were positive at baseline and the mean slope increased substantially and significantly during dobutamine infusion. In patients with heart failure, the heart rate versus LV dP/dt(max) relations were depressed and flattened without a descending limb. Dobutamine infusion shifted this relation upward slightly, without increase in mean slope, indicating lack of amplification. The rate of isovolumic relaxation significantly decreased as heart rate increased at baseline and was further shortened by dobutamine. In patients with heart failure, a depressed and flattened relation between heart rate and LV dP/dt(max) (force-frequency effect) did not show the amplification of myocardial contractility by beta-adrenergic stimulation observed in the normal heart. This abnormality in control of the force-frequency relation undoubtedly plays an important role in the impairment of cardiac function during exercise in heart failure.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Aged
  • Cardiac Pacing, Artificial
  • Cardiomyopathy, Dilated / physiopathology*
  • Dobutamine / pharmacology
  • Hemodynamics
  • Humans
  • Male
  • Middle Aged
  • Myocardial Contraction / physiology*
  • Receptors, Adrenergic, beta / physiology*
  • Ventricular Dysfunction, Left / physiopathology*
  • Ventricular Function, Left / physiology
  • Ventricular Pressure


  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta
  • Dobutamine