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1.5 The Effect of Ivabradine on Plaque Size, Biomechanics, and Microvasculature in Atherosclerotic Rabbits



Atherosclerotic plaque development is associated with increased oxidative stress, that promotes angiogenesis, lipid oxidation and uptake, and ensues cell death. In addition, biomechanical stress, i.e. blood-pressure variations with every heart beat, may further enhance plaque vulnerability. Ivabradine, a heart-rate lowering drug, is associated with reduced oxidative stress and diminished atherosclerotic plaque formation in mice, yet it’s role on plaque microvasculature and biomechanical stress is unknown.


Endothelial denudation (balloon-injury) was performed on the abdominal aorta of 18 New-Zealand-rabbits fed with a high cholesterol diet for 14 weeks. Nine rabbits received ivabradine (17 mg/kg/d) within drinking water throughout the study. Dynamic contrast-enhanced MRI was performed to quantify plaque size and microvasculature (area-undertime-concentration curve, AUC). Blood pressure and relative distension were measured using a pressure catheter and high frame-rate ultrasound.


Systolic, diastolic, and pulse pressure, and (relative) distension were similar between the ivabradine and control group (all p>0.25). But, due to 15%-reduction in heart-rate (p = 0.03), the accumulated biomechanical stress on the plaque is lower in the ivabradine group. MRI plaque size was similar between the groups (p = 1.0). AUC was 25% lower for ivabradine-treated animals (p = 0.03). Linear regression showed a negative trend between heart-rate and AUC when adjusting for ivabradine (p = 0.1).


Ivabradine led to lowered AUC on MRI, indicating decreased plaque microvasculature, which is thought to be an important determinant of reduced plaque vulnerability. Ivabradine did not lead to reduced plaque size, despite reduced accumulated biomechanical stress. Upcoming histological analysis might further unravel the effect of ivabradine on atherosclerosis.

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Hermeling, E., Van Hoof, R.H.M., Salzmann, J. et al. 1.5 The Effect of Ivabradine on Plaque Size, Biomechanics, and Microvasculature in Atherosclerotic Rabbits. Artery Res 8, 122–123 (2014).

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