{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:55:48Z","timestamp":1792065348032,"version":"4.4.0"},"reference-count":16,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000364","name":"Stroke Association","doi-asserted-by":"publisher","award":["SAPDF 21\\100029 + SCLfMP25\\100006"],"award-info":[{"award-number":["SAPDF 21\\100029 + SCLfMP25\\100006"]}],"id":[{"id":"10.13039\/501100000364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206589\/Z\/17\/Z"],"award-info":[{"award-number":["206589\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cerebral pulsatility is a key index of cerebral haemodynamics, a central determinant of intravascular shear stress within intracranial vessels, and is associated with cerebral small vessel disease. It increases with a spontaneously falling heart rate, but the effect of altering heart rates on cerebral haemodynamics is unknown. We therefore tested whether increasing paced heart rate would reduce middle cerebral artery Gosling's pulsatility index (PI)on transcranial ultrasound, during emergency or elective implantation of a pacemaker for bradycardia. In 20 participants (14 males, mean age 78), paced heart rate was increased from 50\u00a0bpm or the individual's resting heart rate up to 100\u00a0bpm in 10\u00a0bpm increments. Cerebral pulsatility was strongly and inversely associated with heart rate, with an average reduction in PI of 0.07 per 10 beats per minute in unadjusted analyses, and 0.08 in mixed effects linear models adjusted for age, sex and cardiovascular risk factors (\n                    <jats:italic>P\u00a0<\/jats:italic>\n                    &lt;\u00a00.001). Increasing heart rate reduced peak systolic velocity by 2.51\u00a0cm\/s per 10\u00a0bpm and increased end\u2010diastolic velocity by 1.26\u00a0cm\/s per 10\u00a0bpm, which both mediated the effect on cerebral pulsatility. However, there was no effect on mean velocity. The decrease in peak systolic middle cerebral artery velocity was linear with increasing heart rate, but end\u2010diastolic velocity was maximal at a heart rate of 80\u00a0bpm. Overall, cerebral pulsatility was inversely and causally associated with paced heart rate. Heart rate modification could be a potential intervention to modify cerebral pulsatility, particularly in the context of bradycardia induced by heart block.\n                  <\/jats:p>","DOI":"10.1113\/ep094034","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:26:51Z","timestamp":1792063611000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increasing paced heart rate reduces cerebral pulsatility"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0630-8204","authenticated-orcid":false,"given":"A. J. S.","family":"Webb","sequence":"first","affiliation":[{"name":"Department of Brain Sciences Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Prevention of Stroke and Dementia University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9104-3222","authenticated-orcid":false,"given":"O.","family":"Llwyd","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Prevention of Stroke and Dementia University of Oxford  Oxford UK"},{"name":"Jackie Walton Vascular Studies Unit, John Radcliffe Hospital Oxford University Hospitals NHS Trust  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8453-6133","authenticated-orcid":false,"given":"N.","family":"Herring","sequence":"additional","affiliation":[{"name":"Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"National Audit of Cardiac Rhythm Management (NACRM)","author":"bhuva A.","year":"2025"},{"issue":"18","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1056\/NEJM199910283411804","article-title":"Heart\u2010rate recovery immediately after exercise as a predictor of mortality","volume":"341","author":"Cole C. R.","year":"1999","journal-title":"New England Journal of Medicine"},{"issue":"35","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.1093\/eurheartj\/ehab364","article-title":"2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy","volume":"42","author":"Glikson M.","year":"2021","journal-title":"European Heart Journal"},{"issue":"1","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1159\/000338247","article-title":"Effect of cilostazol in acute lacunar infarction based on pulsatility index of transcranial Doppler (ECLIPse): A multicenter, randomized, double\u2010blind, placebo\u2010controlled trial","volume":"69","author":"Han S. W.","year":"2013","journal-title":"European Neurology"},{"issue":"19","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1056\/NEJMoa043012","article-title":"Heart\u2010rate profile during exercise as a predictor of sudden death","volume":"352","author":"Jouven X.","year":"2005","journal-title":"New England Journal of Medicine"},{"issue":"1","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1136\/jnnp.69.1.48","article-title":"Reduced cerebral blood flow in white matter in ischaemic leukoaraiosis demonstrated using quantitative exogenous contrast based perfusion MRI","volume":"69","author":"Markus H. S.","year":"2000","journal-title":"Journal of Neurology, Neurosurgery, and Psychiatry"},{"issue":"6","key":"e_1_2_10_8_1","doi-asserted-by":"crossref","DOI":"10.1002\/brb3.2176","article-title":"Cerebral blood flow impairment and cognitive decline in heart failure","volume":"11","author":"Ovsenik A.","year":"2021","journal-title":"Brain and Behavior"},{"issue":"1","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1177\/0271678X18803956","article-title":"Small vessel disease is associated with altered cerebrovascular pulsatility but not resting cerebral blood flow","volume":"40","author":"Shi Y.","year":"2020","journal-title":"Journal of Cerebral Blood Flow and Metabolism"},{"issue":"12","key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1212\/WNL.0b013e31826b951e","article-title":"Age\u2010 and sex\u2010specific rates of leukoaraiosis in TIA and stroke patients: Population\u2010based study","volume":"79","author":"Simoni M.","year":"2012","journal-title":"Neurology"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2023.1254209","article-title":"Low\u2010frequency oscillations in the brain show differential regional associations with severity of cerebral small vessel disease: A systematic review","volume":"17","author":"Thomas J.","year":"2023","journal-title":"Frontiers in Neuroscience"},{"issue":"6","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1177\/0271678X20969984","article-title":"Physiological determinants of residual cerebral arterial pulsatility on best medical treatment after TIA or minor stroke","volume":"41","author":"Webb A. J.","year":"2020","journal-title":"Journal of Cerebral Blood Flow and Metabolism"},{"issue":"6","key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1161\/STROKEAHA.115.012411","article-title":"Magnetic resonance imaging measurement of transmission of arterial pulsation to the brain on propranolol versus amlodipine","volume":"47","author":"Webb A. J.","year":"2016","journal-title":"Stroke"},{"issue":"10","key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1161\/STROKEAHA.112.655837","article-title":"Increased cerebral arterial pulsatility in patients with leukoaraiosis: Arterial stiffness enhances transmission of aortic pulsatility","volume":"43","author":"Webb A. J.","year":"2012","journal-title":"Stroke"},{"issue":"6","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1097\/HJH.0000000000002033","article-title":"Effects of vasodilating medications on cerebral haemodynamics in health and disease: Systematic review and meta\u2010analysis","volume":"37","author":"Webb A. J. S.","year":"2019","journal-title":"Journal of Hypertension"},{"issue":"4","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1161\/STROKEAHA.121.035560","article-title":"Aortic stiffness, pulse pressure and cerebral pulsatility progress despite best medical management: The OXVASC cohort","volume":"53","author":"Webb A. J. S.","year":"2021","journal-title":"Stroke"},{"issue":"6","key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1002\/ana.26480","article-title":"Low heart rate is associated with cerebral pulsatility after TIA or minor stroke","volume":"92","author":"Webb A. J. S.","year":"2022","journal-title":"Annals of Neurology"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP094034","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/EP094034","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP094034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:26:54Z","timestamp":1792063614000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP094034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":16,"alternative-id":["10.1113\/EP094034"],"URL":"https:\/\/doi.org\/10.1113\/ep094034","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]},"assertion":[{"value":"2026-05-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"EP094034"}}