Adrenergic effects on force–frequency relationship: a pivotal role for the cardiac intrinsic systems

Aim:  The force–frequency relationship (F–FR) is an important intrinsic regulatory mechanism of cardiac contractility. The involvement of autonomic nervous system in this physiological aspect of cardiac control remains unclear. The aim of the study was to evaluate the role of extrinsic and intrinsic cardiac adrenergic innervations on the heart rate (HR)-related positive inotropic response. Methods:  Twenty-four dogs were anesthetized and acutely instrumented to monitor and record ECG, systemic and left ventricular pressures and derivatives, and to pace the heart at 130, 150, 170, 190 and 210 bpm, in order to construct the F–FR curve. Animals were randomly assigned to four groups (n = 6 each): vehicle (V), ganglion-blocked (G-B), β-blocked (β-B) and ganglion-blocked plus β-blocked (G-B + β-B). Results:  Vehicle treated animals presented the classical F–FR. In the β-B group F–FR was blunted, but never fully suppressed. The G-B treated animals showed a bell-shape response curve of the induced inotropic effect with the zenith at 170 bpm: the first part of the curve resembling the control one, followed by a rapid decline toward baseline value. The co-administration of G-B and β-B agents reversed the contractile response to HR rise with a curve resembling the negative F–FR curve observed in the failing heart. Conclusion:  The F–FR appeared to be constituted by two consecutive mechanisms: first depolarization-rate dependent, and a second catecholamine-dependent. The natural consequence of these observations is that the full expression of F–FR needs an intact adrenergic system.