{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:37:58Z","timestamp":1790617078913,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T00:00:00Z","timestamp":1694217600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Brain perfusion is sensitive to changes in CO<jats:sub>2<\/jats:sub> levels (CO<jats:sub>2<\/jats:sub> reactivity). Previously, we showed a pathological cerebral blood flow (CBF) reduction in the majority of myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) patients during orthostatic stress. Limited data are available on the relation between CO<jats:sub>2<\/jats:sub> and CBF changes in ME\/CFS patients. Therefore, we studied this relation between ME\/CFS patients and healthy controls (HC) during tilt testing. In this retrospective study, supine and end\u2010tilt CBF, as measured by extracranial Doppler flow, were compared with P<jats:sub>ET<\/jats:sub>CO<jats:sub>2<\/jats:sub> data in female patients either with a normal heart rate and blood pressure (HR\/BP) response or with postural orthostatic tachycardia syndrome (POTS), and in HC. Five hundred thirty\u2010five female ME\/CFS patients and 34 HC were included. Both in supine position and at end\u2010tilt, there was a significant relation between CBF and P<jats:sub>ET<\/jats:sub>CO<jats:sub>2<\/jats:sub> in patients (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.0001), without differences between patients with a normal HR\/BP response and with POTS. The relations between the %CBF change and the P<jats:sub>ET<\/jats:sub>CO<jats:sub>2<\/jats:sub> reduction were both significant in patients and HC (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.0001 and <jats:italic>p<\/jats:italic>\u00a0=\u20090.0012, respectively). In a multiple regression analysis, the patient\/HC status and P<jats:sub>ET<\/jats:sub>CO<jats:sub>2<\/jats:sub> predicted CBF. The contribution of the P<jats:sub>ET<\/jats:sub>CO<jats:sub>2<\/jats:sub> to CBF changes was limited, with low adjusted <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup> values. In female ME\/CFS patients, CO2 reactivity, as measured during orthostatic stress testing, is similar to that of HC and is independent of the type of hemodynamic abnormality. However, the influence of CO<jats:sub>2<\/jats:sub> changes on CBF changes is modest in female ME\/CFS patients.<\/jats:p>","DOI":"10.14814\/phy2.15639","type":"journal-article","created":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T07:44:25Z","timestamp":1694245465000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Influence of end\u2010tidal <scp>CO<sub>2<\/sub><\/scp> on cerebral blood flow during orthostatic stress in controls and adults with myalgic encephalomyelitis\/chronic fatigue syndrome"],"prefix":"10.14814","volume":"11","author":[{"given":"C. (Linda) M. C.","family":"van Campen","sequence":"first","affiliation":[{"name":"Stichting CardioZorg  Hoofddorp The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freek W. A.","family":"Verheugt","sequence":"additional","affiliation":[{"name":"Onze Lieve Vrouwe Gasthuis (OLVG)  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans C.","family":"Visser","sequence":"additional","affiliation":[{"name":"Stichting CardioZorg  Hoofddorp The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2012.08.013"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20110077"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2011.02428.x"},{"key":"e_1_2_10_5_1","volume-title":"The cerebral circulation","author":"Cipolla M. J.","year":"2010"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.605618"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.02824"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajh.2008.368"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2002.282.1.H66"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-0353-1_17"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3283279860"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2011.02.004"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-121-12-199412150-00009"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c180021"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20090055"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2008.08.017"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.10.015"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI101680"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI101995"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra012457"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.03.047"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-54165-1_5"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2015.09.013"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31824f94ed"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00527.2014"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.2741\/4698"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781118445112.stat06627"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-200606000-00001"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-5918-6-2"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03289-8"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2011.10.030"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0204419"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.29.9.1876"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2003.08.022"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6963-3-25"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.204461"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.230425"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.12633"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2015.03.029"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.03.002"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12516"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2013.04.045"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.642710"},{"key":"e_1_2_10_44_1","unstructured":"Statistics L.(2015).Multiple regression using SPSS Statistics. Statistical Tutorials and Software Guides. Retrieved fromhttps:\/\/statistics.laerd.com\/"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01359.2005"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00994.2011"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00377.2018"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.008854"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9629(15)40790-6"},{"key":"e_1_2_10_50_1","first-page":"225","article-title":"Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome","volume":"12","author":"Tanaka S.","year":"2003","journal-title":"International Journal of Molecular Medicine"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01211.2010"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1566-0702(00)00205-8"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14234"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-002-0014-1"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.2174\/157016112798829760"},{"key":"e_1_2_10_56_1","first-page":"4","article-title":"Blood volume status in ME\/CFS correlates with the presence or absence of orthostatic symptoms: Preliminary results","volume":"6","author":"Campen C(L). M. C.","year":"2018","journal-title":"Frontiers in Pediatrics"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare8040394"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare8020169"},{"key":"e_1_2_10_59_1","first-page":"16","article-title":"Validation of the severity of myalgic encephalomyelitis\/chronic fatigue syndrome by other measures than history: Activity bracelet, cardiopulmonary exercise testing and a validated activity questionnaire: SF\u201036","volume":"8","author":"Campen C(L). M. C.","year":"2020","journal-title":"Healthcare (Basel)"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina58010051"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cnp.2020.01.003"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.4236\/ijcm.2018.95032"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cnp.2018.02.004"},{"key":"e_1_2_10_64_1","first-page":"1","article-title":"The abnormal cardiac index and stroke volume index changes during a normal tilt table test in ME\/CFS patients compared to healthy volunteers, are not related to deconditioning","volume":"2","author":"Campen C(L) M. C.","year":"2018","journal-title":"Journal of Thrombosis and Circulation"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.4236\/ijcm.2018.911067"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.228551"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-021-03143-3"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.153"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051515"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.15639","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T10:29:16Z","timestamp":1707301756000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.15639"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9]]},"references-count":68,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.14814\/phy2.15639"],"URL":"https:\/\/doi.org\/10.14814\/phy2.15639","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"value":"2051-817X","type":"print"},{"value":"2051-817X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9]]},"assertion":[{"value":"2022-11-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15639"}}