{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T11:44:58Z","timestamp":1793619898733,"version":"4.5.0"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center for Machine Learning and Health"},{"name":"Center for Machine Learning and Health"},{"name":"Pennsylvania Infrastructure Technology Alliance"},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["17SDG33700047"],"award-info":[{"award-number":["17SDG33700047"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21-EB024675"],"award-info":[{"award-number":["R21-EB024675"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The brain\u2019s ability to maintain cerebral blood flow approximately constant despite cerebral perfusion pressure changes is known as cerebral autoregulation (CA) and is governed by vasoconstriction and vasodilation. Cerebral perfusion pressure is defined as the pressure gradient between arterial blood pressure and intracranial pressure. Measuring CA is a challenging task and has created a variety of evaluation methods, which are often categorized as static and dynamic CA assessments. Because CA is quantified as the performance of a regulatory system and no physical ground truth can be measured, conflicting results are reported. The conflict further arises from a lack of healthy volunteer data with respect to cerebral perfusion pressure measurements and the variety of diseases in which CA ability is impaired, including stroke, traumatic brain injury and hydrocephalus. To overcome these differences, we present a healthy non-human primate model in which we can control the ability to autoregulate blood flow through the type of anesthesia (isoflurane vs fentanyl). We show how three different assessment methods can be used to measure CA impairment, and how static and dynamic autoregulation compare under challenges in intracranial pressure and blood pressure. We reconstructed Lassen\u2019s curve for two groups of anesthesia, where only the fentanyl anesthetized group yielded the canonical shape. Cerebral perfusion pressure allowed for the best distinction between the fentanyl and isoflurane anesthetized groups. The autoregulatory response time to induced oscillations in intracranial pressure and blood pressure, measured as the phase lag between intracranial pressure and blood pressure, was able to determine autoregulatory impairment in agreement with static autoregulation. Static and dynamic CA both show impairment in high dose isoflurane anesthesia, while low isoflurane in combination with fentanyl anesthesia maintains CA, offering a repeatable animal model for CA studies.<\/jats:p>","DOI":"10.1371\/journal.pone.0245291","type":"journal-article","created":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T09:33:00Z","timestamp":1610184780000},"page":"e0245291","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Comparison of static and dynamic cerebral autoregulation under anesthesia influence in a controlled animal model"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-4134","authenticated-orcid":true,"given":"Alexander","family":"Ruesch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepshikha","family":"Acharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1192-9942","authenticated-orcid":true,"given":"Matthew A.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana M.","family":"Kainerstorfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"key":"pone.0245291.ref001","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1093\/bja\/48.8.719","article-title":"Physiology of cerebral blood flow","volume":"48","author":"NA Lassen","year":"1976","journal-title":"BrJ Anaesth"},{"key":"pone.0245291.ref002","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1152\/physrev.1959.39.2.183","article-title":"Cerebral blood flow and oxygen consumption in man","volume":"39","author":"NA Lassen","year":"1959","journal-title":"Physiol Rev"},{"key":"pone.0245291.ref003","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1097\/01.PCC.0000123545.69133.C3","article-title":"Cerebral autoregulation in pediatric traumatic brain injury","volume":"5","author":"MS Vavilala","year":"2004","journal-title":"Pediatr Crit Care Med"},{"key":"pone.0245291.ref004","doi-asserted-by":"crossref","first-page":"E7","DOI":"10.3171\/FOC.2008.25.10.E7","article-title":"Cerebral pressure autoregulation in traumatic brain injury","volume":"25","author":"N Focus","year":"2008","journal-title":"Neurosurg Focus"},{"key":"pone.0245291.ref005","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3171\/2017.7.JNS17216","article-title":"Cerebral autoregulation, cerebrospinal fluid outflow resistance, and outcome following cerebrospinal fluid diversion in normal pressure hydrocephalus","volume":"130","author":"AD Lalou","year":"2019","journal-title":"J Neurosurg"},{"key":"pone.0245291.ref006","first-page":"467","article-title":"Dynamic cerebral autoregulation and beat to beat blood pressure control are impaired in acute ischaemic stroke","volume":"72","author":"PJ Eames","year":"2002","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0245291.ref007","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1227\/NEU.0000000000001432","article-title":"Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition","volume":"80","author":"N Carney","year":"2017","journal-title":"Neurosurgery"},{"key":"pone.0245291.ref008","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1097\/PCC.0000000000001735","article-title":"Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition","volume":"20","author":"PM Kochanek","year":"2019","journal-title":"Pediatr Crit Care Med. 3rd ed"},{"key":"pone.0245291.ref009","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/3-211-32318-X_6","article-title":"Association between outcome, cerebral pressure reactivity and slow ICP waves following head injury","author":"M Balestreri","year":"2005","journal-title":"Acta Neurochir Suppl"},{"key":"pone.0245291.ref010","doi-asserted-by":"crossref","first-page":"008","DOI":"10.1385\/NCC:4:1:008","article-title":"Impact of Intracranial Pressure and Cerebral Perfusion Pressure on Severe Disability and Mortality After Head Injury","volume":"4","author":"M Balestreri","year":"2006","journal-title":"Neurocrit Care"},{"key":"pone.0245291.ref011","doi-asserted-by":"crossref","first-page":"1014 LP","DOI":"10.1161\/01.STR.26.6.1014","article-title":"Comparison of Static and Dynamic Cerebral Autoregulation Measurements","volume":"26","author":"FP Tiecks","year":"1995","journal-title":"Stroke"},{"key":"pone.0245291.ref012","doi-asserted-by":"crossref","first-page":"5623","DOI":"10.1113\/JP274304","article-title":"Claassen JAHR. Lack of linear correlation between dynamic and steady-state cerebral autoregulation","volume":"595","author":"DLK de Jong","year":"2017","journal-title":"J Physiol"},{"key":"pone.0245291.ref013","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1177\/0271678X19871013","article-title":"Assessment of cerebral autoregulation in stroke: A systematic review and meta-analysis of studies at rest","volume":"39","author":"K Intharakham","year":"2019","journal-title":"J Cereb Blood Flow Metab"},{"key":"pone.0245291.ref014","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.anclin.2016.04.002","article-title":"Cerebral Blood Flow Autoregulation and Dysautoregulation","volume":"34","author":"WM Armstead","year":"2016","journal-title":"Anesth Clin"},{"key":"pone.0245291.ref015","volume-title":"Cerebral Autoregulation: Control of Blood Flow in the Brain","author":"S. Payne","year":"2016"},{"key":"pone.0245291.ref016","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1016\/j.medengphy.2014.08.001","article-title":"Static autoregulation in humans: a review and reanalysis","volume":"36","author":"T Numan","year":"2014","journal-title":"Med Eng Phys"},{"key":"pone.0245291.ref017","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1161\/01.STR.20.1.45","article-title":"Cerebral autoregulation dynamics in humans","volume":"20","author":"R Aaslid","year":"1989","journal-title":"Stroke"},{"key":"pone.0245291.ref018","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1152\/japplphysiol.00068.2013","article-title":"The frequency response of cerebral autoregulation","volume":"115","author":"CD Fraser","year":"2013","journal-title":"J Appl Physiol"},{"key":"pone.0245291.ref019","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/jcbfm.2015.5","article-title":"Cerebral autoregulation in the microvasculature measured with near-infrared spectroscopy","volume":"35","author":"JM Kainerstorfer","year":"2015","journal-title":"J Cereb Blood Flow Metab"},{"key":"pone.0245291.ref020","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3171\/jns.1975.43.4.0385","article-title":"Effects of increased intracranial pressure on cerebral blood volume, blood flow, and oxygen utilization in monkeys","volume":"43","author":"RL Grubb","year":"1975","journal-title":"J Neurosurg"},{"key":"pone.0245291.ref021","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1136\/jnnp.63.6.721","article-title":"Contribution of mathematical modelling to the interpretation of bedside tests of cerebrovascular autoregulation","volume":"63","author":"M Czosnyka","year":"1997","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0245291.ref022","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1097\/00003246-200204000-00002","article-title":"Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury","volume":"30","author":"A Steiner L","year":"2002","journal-title":"Crit Care Med"},{"key":"pone.0245291.ref023","doi-asserted-by":"crossref","first-page":"31411","DOI":"10.1117\/1.NPh.3.3.031411","article-title":"Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods","volume":"3","author":"S Fantini","year":"2016","journal-title":"Neurophotonics"},{"key":"pone.0245291.ref024","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1007\/s00381-016-3143-x","article-title":"Noninvasive methods of detecting increased intracranial pressure","volume":"32","author":"W Xu","year":"2016","journal-title":"Child\u2019s Nerv Syst"},{"key":"pone.0245291.ref025","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3390\/s18020465","article-title":"Intracranial pressure monitoring\u2014review and avenues for development","volume":"18","author":"M Harary","year":"2018","journal-title":"Sensors (Switzerland)"},{"key":"pone.0245291.ref026","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1177\/0271678X19891359","article-title":"Fluctuations in intracranial pressure can be estimated non-invasively using near-infrared spectroscopy in non-human primates","volume":"40","author":"A Ruesch","year":"2020","journal-title":"J Cereb Blood Flow Metab"},{"key":"pone.0245291.ref027","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1364\/BOE.386612","article-title":"Estimating intracranial pressure using pulsatile cerebral blood flow measured with diffuse correlation spectroscopy","volume":"11","author":"A Ruesch","year":"2020","journal-title":"Biomed Opt Express"},{"key":"pone.0245291.ref028","volume-title":"Miller\u2019s Anesthesia","author":"PM Patel","year":"2010","edition":"8"},{"key":"pone.0245291.ref029","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/978-1-59259-835-9_13","article-title":"The effects of anesthetic agents on cardiac function","author":"MK Loushin","year":"2005","journal-title":"Handb Card Anatomy, Physiol Devices"},{"key":"pone.0245291.ref030","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1364\/JOSAA.14.000192","article-title":"Spatially varying dynamical properties of turbid media probed with diffusing temporal light correlation","volume":"14","author":"DA Boas","year":"1997","journal-title":"J Opt Soc Am"},{"key":"pone.0245291.ref031","doi-asserted-by":"crossref","first-page":"5163","DOI":"10.1016\/j.neuroimage.2013.06.017","article-title":"Diffuse correlation spectroscopy for non-invasive, micro-vascular cerebral blood flow measurement","volume":"85","author":"T Durduran","year":"2014","journal-title":"Neuroimage"},{"key":"pone.0245291.ref032","doi-asserted-by":"crossref","first-page":"011009","DOI":"10.1117\/1.NPh.1.1.011009","article-title":"Diffuse correlation spectroscopy for measurement of cerebral blood flow: future prospects","volume":"1","author":"EM Buckley","year":"2014","journal-title":"Neurophotonics"},{"key":"pone.0245291.ref033","doi-asserted-by":"crossref","first-page":"12571","DOI":"10.1364\/OE.17.012571","article-title":"Cerebral hemodynamics in preterm infants during positional intervention measured with diffuse correlation spectroscopy and transcranial Doppler ultrasound","volume":"17","author":"EM Buckley","year":"2009","journal-title":"Opt Express"},{"key":"pone.0245291.ref034","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1364\/BOE.1.000553","article-title":"Validation of diffuse correlation spectroscopy measurements of rodent cerebral blood flow with simultaneous arterial spin labeling MRI; towards MRI-optical continuous cerebral metabolic monitoring","volume":"1","author":"SA Carp","year":"2010","journal-title":"Biomed Opt Express"},{"key":"pone.0245291.ref035","unstructured":"University of Texas at Austin. Non-Human Primate-Specific Anesthesia. Available: https:\/\/research.utexas.edu\/wp-content\/uploads\/sites\/7\/2020\/02\/NHP_Anesthesia_guidance_ARC_010920.pdf"},{"key":"pone.0245291.ref036","unstructured":"University of Minnesota. Anesthesia Guidelines: Non-human Primates, Available: https:\/\/www.researchservices.umn.edu\/services-name\/research-animal-resources\/research-support\/guidelines\/anesthesia-non-human-primates#drugs"},{"key":"pone.0245291.ref037","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/00000542-199507000-00008","article-title":"Dynamic and Static Cerebral Autoregulation during Isoflurane, Desflurane, and Propofol Anesthesia","volume":"83","author":"S Strebel","year":"1995","journal-title":"Anesthesiology"},{"key":"pone.0245291.ref038","first-page":"341","article-title":"Dynamic cerebral autoregulation during sevoflurane anesthesia: A comparison with isoflurane","volume":"88","author":"AC Summors","year":"1999","journal-title":"Anesth Analg"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0245291","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T09:33:50Z","timestamp":1610184830000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0245291"}},"subtitle":[],"editor":[{"given":"Yoko","family":"Hoshi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1,8]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0245291","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,8]]}}}