Force-frequency effect is a powerful determinant of myocardial contractility in the mouse

The effects of heart rate (HR) on myocardial contractility in the mouse heart in situ were first investigated in open-chest mice (n = 7) by left ventricular (LV) catheter-tip micromanometry. HR %vas first slowed with a sinus node inhibitor (zatebradine), and atrial pacing to progressively increase the HR caused a positive inotropic response (assessed by maximum positive first derivative of LV pressure, LV dP/d«max) up to a HR of 282 beats/min with the onset of a descending limb of the forcefrequency relation (FFR) at 332 beats/min. β-Adrenergic receptor stimulation (dobutamine) shifted upward and significantly steepened the positive FFR and increased HR at the onset of the descending limb to 402 beats/min. HR and LV dP/d-4max were then studied in closed-chest mice without pacing during recovery from anesthesia (n = 7), and during rest and intermittent physical activity the FFR was linear and positive up to 600 beats/min. HR was then progressively slowed with zatebradine, and the points at rest and during activity fell on the same linear relation. Thus we conclude the following: 1 ) in the open-chest anesthetized mouse, a positive FFR was amplified by β-adrenergic receptor stimulation, and 2) in the mouse recovering from anesthesia the sinus node rate remained a critical determinant of myocardial contractility, without a descending limb of the FFR. Copyright ©1997 the American Physiological Society.

Duke Scholars

Author Lan Mao Medicine, Cardiology