{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:37:45Z","timestamp":1788957465310,"version":"build-2803163510"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Recent studies have shown that individuals with sickle cell disease (SCD) exhibit greater vasoconstriction responses to physical autonomic stressors, such as heat pain and cold pain than normal individuals, but this is not the case for mental stress (MTS). We sought to determine whether this anomalous finding for MTS is related to inter-group differences in baseline cardiac and vascular autonomic function. Fifteen subjects with SCD and 15 healthy volunteers participated in three MTS tasks: N-back, Stroop, and pain anticipation (PA). R\u2013R interval (RRI), arterial blood pressure and finger photoplethysmogram (PPG) were continuously monitored before and during these MTS tasks. The magnitude of vasoconstriction was quantified using change in PPG amplitude (PPGa) from the baseline period. To represent basal autonomic function, we assessed both cardiac and vascular arms of the baroreflex during the baseline period. Cardiac baroreflex sensitivity (BRSc) was estimated by applying both the \u201csequence\u201d and \u201cspectral\u201d techniques to beat-to-beat measurements of systolic blood pressure and RRIs. The vascular baroreflex sensitivity (BRSv) was quantified using the same approaches, modified for application to beat-to-beat diastolic blood pressure and PPGa measurements. Baseline BRSc was not different between SCD and non-SCD subjects, was not correlated with BRSv, and was not associated with the vasoconstriction responses to MTS tasks. BRSv in both groups was correlated with mean PPGa, and since both baseline PPGa and BRSv were lower in SCD, these results suggested that the SCD subjects were in a basal state of higher sympathetically mediated vascular tone. In both groups, baseline BRSv was positively correlated with the vasoconstriction responses to N-back, Stroop, and PA. After adjusting for differences in BRSv within and between groups, we found no difference in the vasoconstriction responses to all three mental tasks between SCD and non-SCD subjects. The implications of these findings are significant in subjects with SCD since vasoconstriction reduces microvascular flow and prolongs capillary transit time, increasing the likelihood for vaso-occlusive crisis (VOC) to be triggered by exposure to stressful events.<\/jats:p>","DOI":"10.3389\/fphys.2021.698209","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T05:32:10Z","timestamp":1636003930000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Vasoconstriction Response to Mental Stress in Sickle Cell Disease: The Role of the Cardiac and Vascular Baroreflexes"],"prefix":"10.3389","volume":"12","author":[{"given":"Wanwara","family":"Thuptimdang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payal","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Khaleel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sunwoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saranya","family":"Veluswamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta M.","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Coates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C. K.","family":"Khoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1002\/jcp.22195","article-title":"Sickle cell anemia and vascular dysfunction: the nitric oxide connection.","volume":"224","author":"Akinsheye","year":"2010","journal-title":"J. Cell. Physiol."},{"key":"B2","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.bpa.2014.08.006","article-title":"Photoplethysmography.","volume":"28","author":"Alian","year":"2014","journal-title":"Best Pract. Res. Clin. Anaesthesiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3647","DOI":"10.1182\/blood-2012-04-383430","article-title":"Sickle cell pain: a critical reappraisal.","volume":"120","author":"Ballas","year":"2012","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"B4","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1109\/TBME.1986.325789","article-title":"An efficient algorithm for spectral analysis of heart rate variability","author":"Berger","year":"1986","journal-title":"Proceedings of the IEEE Transactions on Biomedical Engineering"},{"key":"B5","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s11517-013-1111-0","article-title":"Determinants of vascular and cardiac baroreflex sensitivity values in a random population sample.","volume":"52","author":"Borgers","year":"2014","journal-title":"Med. Biol. Eng. Comput."},{"key":"B6","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1113\/jphysiol.1992.sp019269","article-title":"Sympathetic activity is influenced by task difficulty and stress perception during mental challenge in humans.","volume":"454","author":"Callister","year":"1992","journal-title":"J. Physiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1002\/cphy.c140030","article-title":"Sympathoneural and adrenomedullary responses to mental stress.","volume":"5","author":"Carter","year":"2011","journal-title":"Compr. Physiol."},{"key":"B8","doi-asserted-by":"crossref","first-page":"R681","DOI":"10.1152\/ajpregu.00896.2007","article-title":"Sympathetic responses to vestibular activation in humans.","volume":"294","author":"Carter","year":"2008","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12463","article-title":"Autonomic responses to cold face stimulation in sickle cell disease: a time-varying model analysis.","volume":"3","author":"Chalacheva","year":"2015","journal-title":"Physiol. Rep."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00381","article-title":"Sickle cell disease subjects have a distinct abnormal autonomic phenotype characterized by peripheral vasoconstriction with blunted cardiac response to head-up tilt.","volume":"10","author":"Chalacheva","year":"2019","journal-title":"Front. Physiol."},{"key":"B11","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1002\/(SICI)1097-0258(19971030)16:20<2349::AID-SIM667>3.0.CO;2-E","article-title":"Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data.","volume":"16","author":"Cnaan","year":"1997","journal-title":"Stat. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"251","DOI":"10.3233\/ch-189011","article-title":"Autonomic nervous system involvement in sickle cell disease.","volume":"68","author":"Coates","year":"2018","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"B13","doi-asserted-by":"publisher","first-page":"R429","DOI":"10.1152\/ajpregu.00051.2015","article-title":"Central mechanisms regulating coordinated cardiovascular and respiratory function during stress and arousal.","volume":"309","author":"Dampney","year":"2015","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2017.00461","article-title":"Resetting of the baroreflex control of sympathetic vasomotor activity during natural behaviors: description and conceptual model of central mechanisms.","volume":"11","author":"Dampney","year":"2017","journal-title":"Front. Neurosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.jpeds.2011.07.018","article-title":"Markers of severe vaso-occlusive painful episode frequency in children and adolescents with sickle cell anemia.","volume":"160","author":"Darbari","year":"2012","journal-title":"J. Pediatr."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079923","article-title":"Severe painful vaso-occlusive crises and mortality in a contemporary adult sickle cell anemia cohort study.","volume":"8","author":"Darbari","year":"2013","journal-title":"PLoS One"},{"key":"B17","doi-asserted-by":"publisher","first-page":"H1788","DOI":"10.1152\/ajpheart.00942.2010","article-title":"Attenuation of sympathetic baroreflex sensitivity during the onset of acute mental stress in humans.","volume":"300","author":"Durocher","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1002\/ajh.20107","article-title":"Vasoactive factors in sickle cell disease: in vitro evidence for endothelin-1-mediated vasoconstriction.","volume":"76","author":"Ergul","year":"2004","journal-title":"Am. J. Hematol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1093\/jpepsy\/jsg026","article-title":"Daily stress and mood and their association with pain, health-care use, and school activity in adolescents with sickle cell disease.","volume":"28","author":"Gil","year":"2003","journal-title":"J. Pediatr. Psychol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1037\/0278-6133.23.3.267","article-title":"Daily mood and stress predict pain, health care use, and work activity in African American adults with sickle-cell disease.","volume":"23","author":"Gil","year":"2004","journal-title":"Health Psychol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"H1203","DOI":"10.1152\/ajpheart.00501.2019","article-title":"Sympathetic baroreflex sensitivity is inversely related to vascular transduction in men but not women.","volume":"317","author":"Hissen","year":"2019","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B22","doi-asserted-by":"crossref","first-page":"H1113","DOI":"10.1152\/ajpheart.1997.272.3.H1113","article-title":"Effects of Stroop color-word conflict test on the autonomic nervous system responses.","volume":"272","author":"Hoshikawa","year":"1997","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B23","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1002\/ajh.24858","article-title":"Individuals with sickle cell disease have a significantly greater vasoconstriction response to thermal pain than controls and have significant vasoconstriction in response to anticipation of pain.","volume":"92","author":"Khaleel","year":"2017","journal-title":"Am. J. Hematol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1152\/japplphysiol.00111.2019","article-title":"Respiratory modulation of peripheral vasoconstriction: a modeling perspective.","volume":"127","author":"Khoo","year":"2019","journal-title":"J. Appl. Physiol."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00438","article-title":"Simultaneous characterization of sympathetic and cardiac arms of the baroreflex through sequence techniques during incremental head-up tilt.","volume":"7","author":"Marchi","year":"2016","journal-title":"Front. Physiol."},{"key":"B26","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.autneu.2011.07.011","article-title":"Cardiovascular autonomic dysfunction in sickle cell anemia.","volume":"166","author":"Martins","year":"2012","journal-title":"Auton. Neurosci."},{"key":"B27","doi-asserted-by":"crossref","first-page":"R683","DOI":"10.1152\/ajpregu.2001.281.3.R683","article-title":"Differential control of sympathetic outflow.","volume":"281","author":"Morrison","year":"2001","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.3324\/haematol.2011.047365","article-title":"Frequency of pain crises in sickle cell anemia and its relationship with the sympatho-vagal balance, blood viscosity and inflammation.","volume":"96","author":"Nebor","year":"2011","journal-title":"Haematologica"},{"key":"B29","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1136\/hrt.73.6.517","article-title":"Baroreflex sensitivity and cardiovascular mortality in patients with mild to moderate heart failure.","volume":"73","author":"Osterziel","year":"1995","journal-title":"Heart"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.223776","article-title":"Extracting autonomic information from oscillations in MSNA.","author":"Pagani","year":"2012","journal-title":"J. Physiol."},{"key":"B31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/00004872-200018010-00003","article-title":"How to measure baroreflex sensitivity: from the cardiovascular laboratory to daily life.","volume":"18","author":"Parati","year":"2000","journal-title":"J. Hypertens."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1097\/00004872-200110000-00001","article-title":"Time versus frequency domain techniques for assessing baroreflex sensitivity.","volume":"19","author":"Persson","year":"2001","journal-title":"J. Hypertens."},{"key":"B33","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJM199107043250103","article-title":"Pain in sickle cell disease: rates and risk factors.","volume":"325","author":"Platt","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00688","article-title":"Peripheral resistance baroreflex during incremental bicycle ergometer exercise: characterization and correlation with cardiac baroreflex.","volume":"9","author":"Porta","year":"2018","journal-title":"Front. Physiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1177\/135910530000500109","article-title":"The role of stress and mood in sickle cell disease pain: an analysis of daily diary data.","volume":"5","author":"Porter","year":"2000","journal-title":"J. Health Psychol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1046\/j.1475-0961.2003.00516.x","article-title":"Quantification of inspiratory-induced vasoconstrictive episodes: a comparison of laser Doppler fluxmetry and photoplethysmography.","volume":"23","author":"Rauh","year":"2003","journal-title":"Clin. Physiol. Funct. Imaging"},{"key":"B37","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1016\/S0140-6736(10)61029-X","article-title":"Sickle-cell disease.","volume":"376","author":"Rees","year":"2010","journal-title":"Lancet"},{"key":"B38","doi-asserted-by":"publisher","first-page":"R463","DOI":"10.1152\/ajpregu.00305.2018","article-title":"Relation between resting sympathetic outflow and vasoconstrictor responses to sympathetic nerve bursts: sex differences in healthy young adults.","volume":"316","author":"Robinson","year":"2019","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"5311","DOI":"10.1113\/jphysiol.2011.213074","article-title":"Arterial pressure oscillations are not associated with muscle sympathetic nerve activity in individuals exposed to central hypovolaemia.","volume":"589","author":"Ryan","year":"2011","journal-title":"J. Physiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1164\/rccm.201103-0537OC","article-title":"Peripheral vasoconstriction and abnormal parasympathetic response to sighs and transient hypoxia in sickle cell disease.","volume":"184","author":"Sangkatumvong","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"83","DOI":"10.3324\/haematol.2018.211391","article-title":"Mental stress causes vasoconstriction in subjects with sickle cell disease and in normal controls.","volume":"105","author":"Shah","year":"2020","journal-title":"Haematologica"},{"key":"B42","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1161\/01.CIR.93.5.1043","article-title":"Heart rate variability: standards of measurement, physiological interpretation, and clinical use.","volume":"93","year":"1996","journal-title":"Circulation"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8101690","article-title":"Vaso-occlusion in sickle cell disease: is autonomic dysregulation of the microvasculature the trigger?","volume":"8","author":"Veluswamy","year":"2019","journal-title":"J. Clin. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1182\/blood.2020005045","article-title":"Progressive vasoconstriction with sequential thermal stimulation indicates vascular dysautonomia in sickle cell disease.","volume":"136","author":"Veluswamy","year":"2020","journal-title":"Blood"},{"key":"B45","first-page":"80","article-title":"Comparison of costs to the health sector of comprehensive and episodic health care for sickle cell disease patients.","volume":"110","author":"Yang","year":"1995","journal-title":"Public Health Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"S536","DOI":"10.1016\/j.amepre.2010.01.001","article-title":"Emergency department visits made by patients with sickle cell disease: a descriptive study, 1999\u20132007.","volume":"38","author":"Yusuf","year":"2010","journal-title":"Am. J. Prev. Med."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.698209\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T05:32:18Z","timestamp":1636003938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.698209\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,4]]},"references-count":46,"alternative-id":["10.3389\/fphys.2021.698209"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2021.698209","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,4]]},"article-number":"698209"}}