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1 Laboratoire de Pharmacologie, INSERM E 00.01, Faculté de Médecine Paris Sud, 94270 Le Kremlin-Bicêtre, 2 Service de Cardiologie, Hôpital Antoine Béclère, 92140 Clamart; and 3 Fédération de Cardiologie, Hôpital Henri Mondor, 94000 Créteil, France
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/dtmax 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
(M
O2) 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 M
O2 were similar
between ivabradine and saline but significantly reduced with atenolol.
Thus HR reduction and negative inotropy equally contribute to the
reduction in M
O2 during exercise in the normal heart. The negative inotropy limits the increase in DT
afforded by HR reduction.
metabolic demand; chronotropy; inotropy; diastolic time
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