Abstract
Background Changes in arterial wall viscosity, which dissipates the energy stored within the arterial wall, may contribute to the beneficial effect of heart rate (HR) reduction on arterial stiffness and cardiovascular coupling. However, it has never been assessed in humans and could be altered by aging. We evaluated the effect of a selective HR-lowering agent on carotid arterial wall viscosity and the impact of aging on this effect. Methods and Results This randomized, placebo-controlled, double-blind, crossover study performed in 19 healthy volunteers evaluated the effects of ivabradine (5 mg BID, 1-week) on carotid arterial wall viscosity, mechanics, hemodynamics, and cardiovascular coupling. Arterial wall viscosity was evaluated by the area of the hysteresis loop of the pressure-lumen cross-sectional area relationship, representing the energy dissipated (W(V)), and by the relative viscosity (W(V)/W(E)), with W(E) representing the elastic energy stored. HR reduction by ivabradine increased W(V) and W(E) whereas W(V)/W(E) remained stable. In middle-aged subjects (n=11), baseline arterial stiffness and cardiovascular coupling were less favorable, and W(E) was similar but W(V) and therefore W(V)/W(E) were lower than in youth (n=8). HR reduction increased W(V)/W(E) in middle-aged but not in young subjects, owing to a larger increase in W(V) than W(E). These results were supported by the age-related linear increase in W(V)/W(E) after HR reduction (P=0.009), explained by a linear increase in W(V). Conclusion HR reduction increases arterial wall energy dissipation proportionally to the increase in W(E), suggesting an adaptive process to bradycardia. This mechanism is altered during aging resulting in a larger than expected energy dissipation, the impact of which should be assessed. Registration URL: https://www.clinicaltrials.gov; Unique identifier: 2015/077/HP. URL: https://www. eudract.ema.europa.eu; Unique identifier: 2015-002060-17.