title: Force-frequency effect is a powerful determinant of myocardial contractility in the mouse.
abstract: 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 was 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/dtmax) up to a HR of 282 beats/min with the onset of a descending limb of the force-frequency relation (FFR) at 332 beats/min. beta-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/dtmax 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 beta-adrenergic receptor stimulation, and 20 in the mouse recovering from anesthesia the sinus node rate remained a critical determinant of myocardial contractility, without a descending limb of the FFR.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla 92093-0613, USA.
authors.forename: V
authors.initials: V
authors.lastname: Palakodeti
authors.forename: S
authors.initials: S
authors.lastname: Oh
authors.forename: B H
authors.initials: BH
authors.lastname: Oh
authors.forename: L
authors.initials: L
authors.lastname: Mao
authors.forename: M
authors.initials: M
authors.lastname: Hongo
authors.forename: K L
authors.initials: KL
authors.lastname: Peterson
authors.forename: J
authors.initials: J
authors.lastname: Ross
mesh_terms: D000768:Anesthesia, General; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D004562:Electrocardiography; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects; D008365:Manometry; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D012044:Regression Analysis; D012849:Sinoatrial Node / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D001552:Benzazepines; D002316:Cardiotonic Agents; C043636:zatebradine