{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:51:09Z","timestamp":1753887069772,"version":"3.41.2"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,2,15]]},"abstract":"\n Background<\/jats:title>\n 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\u2010lowering agent on carotid arterial wall viscosity and the impact of aging on this effect.<\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n This randomized, placebo\u2010controlled, double\u2010blind, crossover study performed in 19 healthy volunteers evaluated the effects of ivabradine (5\u00a0mg BID, 1\u2010week) 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\u2010lumen cross\u2010sectional area relationship, representing the energy dissipated (W\n V<\/jats:sub>\n ), and by the relative viscosity (W\n V<\/jats:sub>\n \/W\n E<\/jats:sub>\n ), with W\n E<\/jats:sub>\n representing the elastic energy stored.\n <\/jats:p>\n \n HR reduction by ivabradine increased W\n V<\/jats:sub>\n and W\n E<\/jats:sub>\n whereas W\n V<\/jats:sub>\n \/W\n E<\/jats:sub>\n remained stable. In middle\u2010aged subjects (n=11), baseline arterial stiffness and cardiovascular coupling were less favorable, and W\n E<\/jats:sub>\n was similar but W\n V<\/jats:sub>\n and therefore W\n V<\/jats:sub>\n \/W\n E<\/jats:sub>\n were lower than in youth (n=8). HR reduction increased W\n V<\/jats:sub>\n \/W\n E<\/jats:sub>\n in middle\u2010aged but not in young subjects, owing to a larger increase in W\n V<\/jats:sub>\n than W\n E<\/jats:sub>\n . These results were supported by the age\u2010related linear increase in W\n V<\/jats:sub>\n \/W\n E<\/jats:sub>\n after HR reduction (\n P<\/jats:italic>\n =0.009), explained by a linear increase in W\n V<\/jats:sub>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n HR reduction increases arterial wall energy dissipation proportionally to the increase in W\n E<\/jats:sub>\n , 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.\n <\/jats:p>\n <\/jats:sec>\n \n Registration<\/jats:title>\n \n URL:\n https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n ; Unique identifier: 2015\/077\/HP. URL:\n https:\/\/www<\/jats:ext-link>\n . eudract.ema.europa.eu; Unique identifier: 2015\u2010002060\u201017.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.121.023409","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T14:27:12Z","timestamp":1643898432000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Adaptation of Arterial Wall Viscosity to the Short\u2010Term Reduction of Heart Rate: Impact of Aging"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6026-9958","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Roca","sequence":"first","affiliation":[{"name":"Department of Pharmacology Rouen University Hospital Rouen France"},{"name":"Clinical Investigation Center CIC\u2010CRB 1404 Rouen France"},{"name":"Normandie UniversityUNIROUENInserm U1096 Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mich\u00e8le","family":"Iacob","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Rouen University Hospital Rouen France"},{"name":"Normandie UniversityUNIROUENInserm U1096 Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Duflot","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Rouen University Hospital Rouen France"},{"name":"Normandie UniversityUNIROUENInserm U1096 Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Donnadieu","sequence":"additional","affiliation":[{"name":"Pharmacy, Unit of Clinical Trials Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Thill","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9r\u00e9my","family":"Bellien","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Rouen University Hospital Rouen France"},{"name":"Clinical Investigation Center CIC\u2010CRB 1404 Rouen France"},{"name":"Normandie UniversityUNIROUENInserm U1096 Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robinson","family":"Joannides","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Rouen University Hospital Rouen France"},{"name":"Clinical Investigation Center CIC\u2010CRB 1404 Rouen France"},{"name":"Normandie UniversityUNIROUENInserm U1096 Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.09.014"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq165"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07462"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000019132.41066.95"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000085199.33254.15"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.34.4.598"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000008067"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.610"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.595496"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000001984"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.060110"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/1755-5922.12323"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.07.027"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199607000-00013"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200409000-00018"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3233\/CH-2008-1069"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1088\/1742-6596\/90\/1\/012010"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00590192"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1961.sp006687"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9290(74)90001-3"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.17.7.1346"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.09870"},{"key":"e_1_3_2_24_2","unstructured":"Armentano R Pessana F Graf S Romero L Fischer EC. Frequency dependance of arterial wall young modulus after de\u2010endothelization. In: Memorias II Congreso Latinoamericano De Ingeneria Biomedica La Habana. 2001."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.76.3.468"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01087.2006"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2019.04.208"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000014"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1406430"},{"key":"e_1_3_2_30_2","volume-title":"Heart Rate Slowing by if Current Inhibition","author":"Savelieva I","year":"2006","unstructured":"Savelieva I, Camm AJ. Heart rate reduction by pharmacological if current inhibition. In: Camm AJ, Tendera M, eds. Heart Rate Slowing by if Current Inhibition. Basel: Karger; 2006."},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06091"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.32.2.360"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.14.7.1223"},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1161\/01.ATV.13.1.90","article-title":"Arterial alterations with aging and high blood pressure. A noninvasive study of carotid and femoral arteries","volume":"13","author":"Benetos A","year":"1993","unstructured":"Benetos A, Laurent S, Hoeks AP, Boutouyrie PH, Safar ME. Arterial alterations with aging and high blood pressure. A noninvasive study of carotid and femoral arteries. Arterioscler Thromb: A J Vasc Biol\/Am Heart Assoc. 1993;13:90\u201397. doi: 10.1161\/01.ATV.13.1.90","journal-title":"Arterioscler Thromb: A J Vasc Biol\/Am Heart Assoc"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2010.04.002"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ultrasmedbio.2003.10.014"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.35.5.1049"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2007.07.007"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000205915.15940.15"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e328364cbba"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000236839.69658.c5"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/ajh.2008.156"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02544.x"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(01)02252-X"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2016.09.054"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e32833da2b2"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.70.1.123"},{"key":"e_1_3_2_48_2","first-page":"H257","article-title":"Release of endothelium\u2010derived relaxing factor is modulated both by frequency and amplitude of pulsatile flow","volume":"261","author":"Hutcheson IR","year":"1991","unstructured":"Hutcheson IR, Griffith TM. Release of endothelium\u2010derived relaxing factor is modulated both by frequency and amplitude of pulsatile flow. Am J Physiol. 1991;261:H257\u2013262. doi: 10.1152\/ajpheart.1991.261.1.H257","journal-title":"Am J Physiol"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2006.04.011"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00304.2006"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2009.09.012"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13220"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.607998"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00582900"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199208001-00022"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000242289.20381.f4"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.108.116509"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1978.58.2.397"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61170-8"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehl254"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.121.023409","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:18:15Z","timestamp":1715599095000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.121.023409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,15]]},"references-count":59,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,2,15]]}},"alternative-id":["10.1161\/JAHA.121.023409"],"URL":"https:\/\/doi.org\/10.1161\/jaha.121.023409","relation":{},"ISSN":["2047-9980"],"issn-type":[{"type":"electronic","value":"2047-9980"}],"subject":[],"published":{"date-parts":[[2022,2,15]]},"assertion":[{"value":"2021-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e023409"}}