{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T16:36:31Z","timestamp":1765211791009,"version":"3.46.0"},"reference-count":22,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: COPD patients may be prone to cerebral small vessel disease resulting in perivascular white matter lesions and consequent cognitive decline. The pathophysiological background of these observations is not completely understood. It is hypothesized that COPD may involve systemic vascular dysfunction extending to the brain. The present study aimed to assess whether acetazolamide-induced cerebral vasoreactivity and cerebrovascular reserve capacity are impaired in patients with COPD. Methods: A total of 17 patients with COPD and 20 healthy control subjects underwent transcranial Doppler monitoring before and after IV administration of 15 mg\/kgBW acetazolamide for 20 min. Cerebrovascular reactivity (CVR) was defined as a percent increase in blood flow velocity in the middle cerebral artery (MBFV) after acetazolamide. Cerebrovascular reserve capacity (CVRC) was defined as the maximal percent change in MBFV during the entire registration. Results: Administration of acetazolamide resulted in a slight decrease in pH and a mild increase in PaCO2 (both p &lt; 0.001) in COPD patients. Absolute MBFV values were consequently higher, and pulsatility indices were lower in control subjects compared to those measured in patients with COPD. The CVR at different time points after acetazolamide and CVRC did not show any difference between COPD patients and control subjects. Conclusions: In the present study, in normocapnic mild and normocapnic moderate COPD patients, cerebrovascular reactivity is not impaired, indicating that in mild stages, cerebral arteriolar function is preserved. Further studies, using patient selection based on different severity stages of the disease, may show whether alteration of the cerebral arteriolar function is responsible for the white matter lesions and cognitive decline observed in severe COPD patients.<\/jats:p>","DOI":"10.3390\/jcm14238535","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T16:20:29Z","timestamp":1765210829000},"page":"8535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cerebrovascular Reactivity to Acetazolamide in Stable COPD Patients"],"prefix":"10.3390","volume":"14","author":[{"given":"P\u00e9ter","family":"Sir\u00f3","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Szab\u00f3-Sz\u0171cs","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikt\u00f3ria","family":"Dud\u00e1s","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ildik\u00f3","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2541-9740","authenticated-orcid":false,"given":"B\u00e9la","family":"F\u00fclesdi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attila","family":"Vask\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"ref_1","unstructured":"GBD 2021 Causes of Death Collaborators (2024). Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990\u20132021: A systematic analysis for the Global Burden of Disease Study 2021. Lancet, 403, 2100\u20132132."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.resinv.2016.07.001","article-title":"Prevalence and burden of comorbidities in Chronic Obstructive Pulmonary Disease","volume":"54","author":"Corlateanu","year":"2016","journal-title":"Respir. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1164\/rccm.201505-0962OC","article-title":"Chronic Obstructive Pulmonary Disease and the Risk of Stroke. The Rotterdam Study","volume":"193","author":"Portegies","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1136\/thx.2009.128082","article-title":"Prevalence of major comorbidities in subjects with COPD and incidence of myocardial infarction and stroke: A comprehensive analysis using data from primary care","volume":"65","author":"Feary","year":"2010","journal-title":"Thorax"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1159\/000091438","article-title":"Pulmonary function, cognitive impairment and brain atrophy in a middle-aged community sample","volume":"21","author":"Sachdev","year":"2006","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Spilling, C.A., Jones, P.W., Dodd, J.W., and Barrick, T.R. (2017). White matter lesions characterise brain involvement in moderate to severe chronic obstructive pulmonary disease, but cerebral atrophy does not. BMC Pulm. Med., 17.","DOI":"10.1186\/s12890-017-0435-1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1164\/rccm.201202-0355OC","article-title":"Brain structure and function in chronic obstructive pulmonary disease: A multimodal cranial magnetic resonance imaging study","volume":"186","author":"Dodd","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1152\/physrev.00028.2024","article-title":"The pathogenesis of cerebral small vessel disease and vascular cognitive impairment","volume":"105","author":"Markus","year":"2025","journal-title":"Physiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1111\/jon.13197","article-title":"Transcranial Doppler cerebrovascular reactivity: Thresholds for clinical significance in cerebrovascular disease","volume":"34","author":"Regenhardt","year":"2024","journal-title":"J. Neuroimaging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.2337\/diab.46.11.1840","article-title":"Impairment of cerebrovascular reactivity in long-term type 1 diabetes","volume":"46","author":"Limburg","year":"1997","journal-title":"Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1097\/MNM.0b013e328351d583","article-title":"Brain perfusion SPECT imaging and acetazolamide challenge in vascular cognitive impairment","volume":"33","author":"Farid","year":"2012","journal-title":"Nucl. Med. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1900164","DOI":"10.1183\/13993003.00164-2019","article-title":"Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: The GOLD science committee report 2019","volume":"53","author":"Singh","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/jon2000103151","article-title":"Gender-related differences in acetazolamide-induced cerebral vasodilatory response: A transcranial Doppler study","volume":"10","author":"Valikovics","year":"2000","journal-title":"J. Neuroimaging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1046\/j.1468-1331.2003.00675.x","article-title":"Acetazolamide as a vasodilatory stimulus in cerebrovascular diseases and in conditions affecting the cerebral vasculature","volume":"10","author":"Settakis","year":"2003","journal-title":"Eur. J. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1378\/chest.102.1.135","article-title":"Cerebral vascular responsiveness in chronic hypercapnia","volume":"102","author":"Clivati","year":"1992","journal-title":"Chest"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R50","DOI":"10.1186\/cc8939","article-title":"Impaired cerebrovascular reactivity in sepsis-associated encephalopathy studied by acetazolamide test","volume":"14","author":"Hallay","year":"2010","journal-title":"Crit. Care."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/epi4.12619","article-title":"Acetazolamide: Old drug, new evidence?","volume":"7","author":"Shukralla","year":"2022","journal-title":"Epilepsia Open"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1159\/000016027","article-title":"The dose-response relationship of acetazolamide on the cerebral blood flow in normal subjects","volume":"10","author":"Grossmann","year":"2000","journal-title":"Cerebrovasc. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s13760-019-01170-y","article-title":"Impaired cerebrovascular reactivity in chronic obstructive pulmonary disease","volume":"119","author":"Hlavati","year":"2019","journal-title":"Acta Neurol. Belg."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Corr\u00eaa, D.I., de-Lima-Oliveira, M., Nogueira, R.C., Carvalho-Pinto, R.M., Bor-Seng-Shu, E., Panerai, R.B., Carvalho, C.R.F., and Salinet, A.S. (2024). Integrative assessment of cerebral blood regulation in COPD patients. Respir. Physiol. Neurobiol., 319.","DOI":"10.1016\/j.resp.2023.104166"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.clinimag.2011.08.021","article-title":"Impact of COPD exacerbation on cerebral blood flow","volume":"36","author":"Yildiz","year":"2012","journal-title":"Clin. Imaging"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1183\/09031936.01.00087501","article-title":"Ventilatory and cerebrovascular responses in normocapnic and hypercapnic COPD patients","volume":"18","author":"Colier","year":"2001","journal-title":"Eur. Respir. J."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/23\/8535\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T16:33:15Z","timestamp":1765211595000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/23\/8535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":22,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["jcm14238535"],"URL":"https:\/\/doi.org\/10.3390\/jcm14238535","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,1]]}}}