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-blockade
on left ventricular relaxation during exercise
1 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; 2 Fédération de Cardiologie, Hôpital Henri Mondor, 94000 Créteil; and 3 Hôpital Antoine Béclère, 92140 Clamart, France
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
BF, pressure asymptote PBF) 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
BF was significantly reduced from 22 ± 1 to
14 ± 2 ms. At rest, atenolol but not ivabradine increased
BF. For similar heart rate reductions during exercise,
atenolol impeded the shortening of BF (23 ± 2 ms)
whereas ivabradine had no effect (15 ± 2 ms). The extent of the
relaxation process (PBF) 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.
ivabradine; atenolol; ventricular function; conscious dogs
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