title: Contributions of heart rate and contractility to myocardial oxygen balance during exercise.
abstract: The respective contributions of heart rate (HR) reduction and left ventricular (LV) negative inotropy to the effects of antianginal drugs are debated. Accordingly, eight instrumented dogs were investigated during exercise at spontaneous and paced HR (250 beats/min) after administration of either saline, atenolol, or ivabradine (selective pacemaker current channel blocker). During exercise, atenolol and ivabradine (both 1 mg/kg iv) similarly reduced HR (-30% from 222 +/- 5 beats/min), and LV mean ejection wall stress was not altered. LV dP/dt(max) was reduced by atenolol but not ivabradine. Diastolic time (DT) was increased by atenolol versus saline (195 +/- 6 vs. 123 +/- 4 ms, respectively) and to a greater extent by ivabradine (233 +/- 11 ms). Myocardial oxygen consumption (MVo(2)) was lower under ivabradine and atenolol versus saline (6.7 +/- 0.6 and 4.7 +/- 0.4 vs. 8.1 +/- 0.6 ml/min, respectively, P < 0.05). Under pacing, DT and MVo(2) were similar between ivabradine and saline but significantly reduced with atenolol. Thus HR reduction and negative inotropy equally contribute to the reduction in MVo(2) during exercise in the normal heart. The negative inotropy limits the increase in DT afforded by HR reduction.
authors.affiliation: Laboratoire de Pharmacologie, INSERM E 00.01, Faculté de Médecine Paris Sud, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Colin
authors.forename: Bijan
authors.initials: B
authors.lastname: Ghaleh
authors.forename: Xavier
authors.initials: X
authors.lastname: Monnet
authors.forename: Jinbo
authors.initials: J
authors.lastname: Su
authors.forename: Luc
authors.initials: L
authors.lastname: Hittinger
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Giudicelli
authors.forename: Alain
authors.initials: A
authors.lastname: Berdeaux
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D006339:Heart Rate / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D000077550:Ivabradine; D009043:Motor Activity / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D000077550:Ivabradine; D001262:Atenolol