Force-frequency relations during heart failure in pigs

Abstract

In isolated cardiac muscle from patients with severe heart failure (HF) the force-frequency relation (FFR) is often negative, but the characteristics of the FFR under basal conditions and its responsiveness to adrenergic stimulation have not been studied in the intact, failing heart. Severe HF was produced in pigs (n = 6) by continuous rapid left ventricular (LV) pacing (225 beats/min). In the conscious resting state, high-fidelity LV pressure and its maximum first derivative (LV dP/dtmax) were obtained over a range of atrial pacing rates (100-225 beats/min) before (control) and after HF. Before HF, the relationship between increased heart rate and LV dP/dtmax (a measure of the FFR) was flat, but during dobutamine infusion the FFR showed a significant positive slope (P < 0.003). After HF, the basal FFR was depressed, but the slope of the FFR was not increased by dobutamine. After HF, responses of dP/dtmax to slowing of HR by a specific sinus node inhibitor confirmed the absence of a negative basal FFR. In conclusion, the basal LV FFR in conscious pigs with severe HF was not negative. Unlike the normal heart, in HF beta-adrenergic receptor stimulation did not amplify the FFR, a phenomenon that could play an important role in the impaired response to exercise in patients with HF.

Systolic and Diastolic Properties of Univentricular Hearts in Children: Insights from Physiologic Indices That Reflect Calcium Cycling

“…Rather, we used physiologic indices that are known to reflect Ca 2ϩ cycling. The phenomenon of Ca 2ϩ release by the SR was studied by the force-frequency relationship (11) and by mechanical restitution of contractility (12). Ca 2ϩ uptake by the SR was studied by evaluating time constant of relaxation () (13) and the relaxation-frequency relationship (14).…”

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.…”

Heart Rate and Heart Failure - Not a Simple Relationship -

“…90 In conscious dogs, positive effects of atrial pacing on LV dP/dtmax are only modest (Figure 2), possibly secondary to decreased preload, 13,66,91,92 and the relationship between HR and LV dP/dtmax is also flat in pigs. 93 Autonomic blockade abolishes any effect of stimulation frequency on LV dP/dtmax. 66,91 A positive effect of increased HR on LV dP/dtmax ((ie, positive force-frequency relationship) becomes more manifest during β-adrenergic activation in pigs, 93 and during exercise in dogs.…”

“…93 Autonomic blockade abolishes any effect of stimulation frequency on LV dP/dtmax. 66,91 A positive effect of increased HR on LV dP/dtmax ((ie, positive force-frequency relationship) becomes more manifest during β-adrenergic activation in pigs, 93 and during exercise in dogs. 94, 95 In human non-failing hearts in situ, atrial pacing from 80 beats/min to 120 or 140 beats/min modestly increases regional myocardial function 96 and LV dP/dtmax.…”