Adrenergic Control of the Force-Frequency Relation

Abstract

This article briefly reviews recent experimental studies which show that beta-adrenergic receptor stimulation produces an important enhancement of the force-frequency relation on myocardial contractility. The basic property of the force-frequency effect to progressively enhance myocardial contractility as heart rate increases is augmented at each level of increasing adrenergic stimulation. This newly described intrinsic mechanism for the control of cardiac inotropic state, graded beta-adrenergic amplification of the force-frequency relation, is strongly manifested during normal exercise and infusion of a beta-adrenergic agonist at rest, and it influences both systolic and diastolic ventricular function. Significant impairment of adrenergic amplification of the force-frequency relation is observed in experimental heart failure and could contribute to impaired cardiac function during stress or exercise in this setting.

Impaired Ca2+ Handling in Perfused Hypertrophic Hearts from Dahl Salt-Sensitive Rats

“…adrenergic stimulation caused a more positive force-frequency relationship (34). These studies demonstrated the importance of SR in establishing the force-frequency relationship.…”

Dissociation of Chronotropic and Inotropic Responses in the Rat Heart During Sympathetic Stimulation

“…Hitherto, negative staircase (ie, the descending limb of function of the force-frequency relation) has been shown at high physiologic frequencies in rabbits and rats, 2,3,22 whereas a positive staircase by increasing HR (ie, enhancement of the force-frequency relation on myocardial contractility) has been demonstrated in dogs, pigs and humans. [22][23][24] In either case of a positive or negative staircase, amplification of the force-frequency effect by infusion of a -adrenergic receptor agonist has been reported. 22 Although this amplification of the force-frequency relation during administration of a -adrenergic agonist may provide an important mechanism influencing contractility, 25,26 it has not been demonstrated whether or not this phenomenon actually works in the sympathetic discharge.…”

“…[22][23][24] In either case of a positive or negative staircase, amplification of the force-frequency effect by infusion of a -adrenergic receptor agonist has been reported. 22 Although this amplification of the force-frequency relation during administration of a -adrenergic agonist may provide an important mechanism influencing contractility, 25,26 it has not been demonstrated whether or not this phenomenon actually works in the sympathetic discharge. The present study showed that augmented sympathetic stimulation led to large increases in HR and contractility, followed by a decrease of the latter irrespective of increased norepinephrine release or the method of coronary perfusion.…”

Low-Dose Amiodarone for Patients With Advanced Heart Failure Who Are Intolerant of Beta-Blockers.

“…Because an increased HR would depress cardiac function in advanced HF through derangement of the force -frequency relation, 19,20 the effect of amiodarone on HR may augment pump function, and assist in tapering the dose of catecholamines or phosphodiesterase inhibitor. In the present study, amiodarone improved NYHA functional class and FS in 10 medically treated patients who were intolerant of -blockers.…”

“…Experimental studies indicate that -adrenergic amplification of the forcefrequency effect on myocardial contractility is impaired in cardiac failure. 19,20 Moreover, isometrically contracting cardiac muscle taken from failing human hearts at the time of cardiac transplantation often shows a descending limb of the relation between increasing contraction frequency and peak tension. 21 Therefore, drugs with a negative chronotropic effect may augment cardiac function with respect to the force -frequency relation during the interim period before the late recovery of cardiac function after myocardial biological changes.…”