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The effect of the heart rate lowering drug Ivabradine on hemodynamics in atherosclerotic mice.

ABSTRACT: The heart rate lowering drug Ivabradine was shown to improve cardiac outcome in patients with previous heart failure. However, in patients without heart failure, no beneficial effect of Ivabradine was observed. Animal studies suggested a preventive effect of Ivabradine on atherosclerosis which was due to an increase in wall shear stress (WSS), the blood flow-induced frictional force exerted on the endothelium, triggering anti-inflammatory responses. However, data on the effect of Ivabradine on WSS is sparse. We aim to study the effect of Ivabradine on (i) the 3D WSS distribution over a growing plaque and (ii) plaque composition. We induced atherosclerosis in ApoE^-/- mice by placing a tapered cast around the right common carotid artery (RCCA). Five weeks after cast placement, Ivabradine was administered via drinking water (15?mg/kg/day) for 2 weeks, after which the RCCA was excised for histology analyses. Before and after Ivabradine treatment, animals were imaged with Doppler Ultrasound to measure blood velocity. Vessel geometry was obtained using contrast-enhanced micro-CT. Time-averaged WSS during systole, diastole and peak WSS was subsequently computed. Ivabradine significantly decreased heart rate (459?±?28 bpm vs. 567?±?32 bpm, p?

SUBMITTER: Xing R

PROVIDER: S-EPMC6143553 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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The effect of the heart rate lowering drug Ivabradine on hemodynamics in atherosclerotic mice.

Xing R R Moerman A M AM Ridwan R Y RY Gaalen K van KV Meester E J EJ van der Steen A F W AFW Evans P C PC Gijsen F J H FJH Van der Heiden K K

Scientific reports 20180918 1

The heart rate lowering drug Ivabradine was shown to improve cardiac outcome in patients with previous heart failure. However, in patients without heart failure, no beneficial effect of Ivabradine was observed. Animal studies suggested a preventive effect of Ivabradine on atherosclerosis which was due to an increase in wall shear stress (WSS), the blood flow-induced frictional force exerted on the endothelium, triggering anti-inflammatory responses. However, data on the effect of Ivabradine on W ...[more]

PMID: 30228313

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Project description:Atherosclerotic vertebrobasilar (VB) occlusive disease is a significant etiology of posterior circulation stroke, with regional hypoperfusion as an important potential contributor to stroke risk.To test the hypothesis that, among patients with symptomatic VB stenosis or occlusion, those with distal blood flow compromise as measured by large-vessel quantitative magnetic resonance angiography (QMRA) are at higher risk of subsequent posterior circulation stroke.A prospective, blinded, longitudinal cohort study was conducted at 5 academic hospital-based centers in the United States and Canada; 82 patients from inpatient and outpatient settings were enrolled. Participants with recent VB transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries underwent large-vessel flow measurement in the VB territory using QMRA. Physicians performing follow-up assessments were blinded to QMRA flow status. Follow-up included monthly telephone calls for 12 months and biannual clinical visits (for a minimum of 12 months, and up to 24 months or the final visit). Enrollment took place from July 1, 2008, to July 31, 2013, with study completion on June 30, 2014; data analysis was performed from October 1, 2014, to April 10, 2015.Standard medical management of stroke risk factors.The primary outcome was VB-territory stroke.Of the 82 enrolled patients, 72 remained eligible after central review of their angiograms. Sixty-nine of 72 patients completed the minimum 12-month follow-up; median follow-up was 23 (interquartile range, 14-25) months. Distal flow status was low in 18 of the 72 participants (25%) included in the analysis and was significantly associated with risk for a subsequent VB stroke (P =?.04), with 12- and 24-month event-free survival rates of 78% and 70%, respectively, in the low-flow group vs 96% and 87%, respectively, in the normal-flow group. The hazard ratio, adjusted for age and stroke risk factors, in the low distal flow status group was 11.55 (95% CI, 1.88-71.00; P =?.008). Medical risk factor management at 6-month intervals was similar between patients with low and normal distal flow. Distal flow status remained significantly associated with risk even when controlling for the degree of stenosis and location.Distal flow status determined using a noninvasive and practical imaging tool is robustly associated with risk for subsequent stroke in patients with symptomatic atherosclerotic VB occlusive disease. Identification of high-risk patients has important implications for future investigation of more aggressive interventional or medical therapies.

Dataset Information

The effect of the heart rate lowering drug Ivabradine on hemodynamics in atherosclerotic mice.

Publications

The effect of the heart rate lowering drug Ivabradine on hemodynamics in atherosclerotic mice.

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