title: Differential effects of heart rate reduction and beta-blockade on left ventricular relaxation during exercise.
abstract: Left ventricular (LV) relaxation is crucial for LV function, especially during exercise. We compared the effects of increasing doses of ivabradine, a selective inward hyperpolarization-activated current inhibitor, and atenolol on the rate and extent of LV relaxation (best fit method: time constant tau(BF), pressure asymptote P(BF)) at rest and during exercise. Eight dogs were chronically instrumented to measure LV pressure and LV wall stresses. During exercise under saline, heart rate increased from 108 +/- 5 to 220 +/- 6 beats/min and tau(BF) was significantly reduced from 22 +/- 1 to 14 +/- 2 ms. At rest, atenolol but not ivabradine increased tau(BF). For similar heart rate reductions during exercise, atenolol impeded the shortening of tau(BF) (23 +/- 2 ms) whereas ivabradine had no effect (15 +/- 2 ms). The extent of the relaxation process (P(BF)) at peak exercise was increased by ivabradine, and to a greater extent by atenolol, compared with saline. Thus, for a similar reduction in heart rate at rest and during exercise, ivabradine, in contrast with atenolol, does not exert any negative lusitropic effect.
authors.affiliation: Département de Pharmacologie, Institut National de la Santé et de la Recherche Médicale E00.01, Faculté de Médecine Paris Sud, 94276 Le Kremlin-Bicêtre Cedex, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Colin
authors.forename: Bijan
authors.initials: B
authors.lastname: Ghaleh
authors.forename: Luc
authors.initials: L
authors.lastname: Hittinger
authors.forename: Xavier
authors.initials: X
authors.lastname: Monnet
authors.forename: Michel
authors.initials: M
authors.lastname: Slama
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Giudicelli
authors.forename: Alain
authors.initials: A
authors.lastname: Berdeaux
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D003243:Consciousness; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D000077550:Ivabradine; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D002316:Cardiotonic Agents; D000077550:Ivabradine; D001262:Atenolol