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

Scientific Reports
R XingK Van der Heiden

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 ...Continue Reading

References

Dec 11, 1999·JAMA : the Journal of the American Medical Association·A M MalekS Izumo
Apr 7, 2004·British Journal of Pharmacology·Xiao-Jun DuAnthony M Dart
Aug 27, 2005·Nature Clinical Practice. Cardiovascular Medicine·C J SlagerP W Serruys
Sep 9, 2005·The New England Journal of Medicine·Giampaolo BucaneveUNKNOWN Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Infection Program
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May 25, 2011·Ultrasound Quarterly·Daniel T GinatVikram Dogra
Sep 20, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Virginie BolducEric Thorin
Jun 6, 2013·Cardiovascular Research·Paul C Evans, Brenda R Kwak
Sep 2, 2014·The New England Journal of Medicine·Kim FoxUNKNOWN SIGNIFY Investigators

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Citations

Aug 11, 2019·Current Topics in Medicinal Chemistry·Yue ZhouKun Sun
Jul 23, 2020·European Heart Journal Supplements : Journal of the European Society of Cardiology·Martin HorváthJosef Veselka

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Software Mentioned

Vascular Modelling Tool Kit ( VMTK
Post
CFD
MeVisLab
Ansys
- Post
Fluent
Matlab
RStudio

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