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Hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease

Sickle cell disease is characterized by chronic hemolytic anemia and vascular inflammation, which can diminish the vasodilatory capacity of the small resistance arteries, making them less adept at regulating cerebral blood flow. Autoregulation maintains adequate oxygen delivery, but when vasodilatio...

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Autores principales: Václavů, Lena, Meynart, Benoit N., Mutsaerts, Henri J.M.M., Petersen, Esben Thade, Majoie, Charles B.L.M., VanBavel, Ed T., Wood, John C., Nederveen, Aart J., Biemond, Bart J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ferrata Storti Foundation 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442969/
https://www.ncbi.nlm.nih.gov/pubmed/30523051
http://dx.doi.org/10.3324/haematol.2018.206094
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author Václavů, Lena
Meynart, Benoit N.
Mutsaerts, Henri J.M.M.
Petersen, Esben Thade
Majoie, Charles B.L.M.
VanBavel, Ed T.
Wood, John C.
Nederveen, Aart J.
Biemond, Bart J.
author_facet Václavů, Lena
Meynart, Benoit N.
Mutsaerts, Henri J.M.M.
Petersen, Esben Thade
Majoie, Charles B.L.M.
VanBavel, Ed T.
Wood, John C.
Nederveen, Aart J.
Biemond, Bart J.
author_sort Václavů, Lena
collection PubMed
description Sickle cell disease is characterized by chronic hemolytic anemia and vascular inflammation, which can diminish the vasodilatory capacity of the small resistance arteries, making them less adept at regulating cerebral blood flow. Autoregulation maintains adequate oxygen delivery, but when vasodilation is maximized, the low arterial oxygen content can lead to ischemia and silent cerebral infarcts. We used magnetic resonance imaging of cerebral blood flow to quantify whole-brain cerebrovascular reserve in 36 adult patients with sickle cell disease (mean age, 31.9±11.3 years) and 11 healthy controls (mean age, 37.4±15.4 years), and we used high-resolution 3D FLAIR magnetic resonance imaging to determine the prevalence of silent cerebral infarcts. Cerebrovascular reserve was calculated as the percentage change in cerebral blood flow after a hemodynamic challenge with acetazolamide. Co-registered lesion maps were used to demonstrate prevalent locations for silent cerebral infarcts. Cerebral blood flow was elevated in patients with sickle cell disease compared to controls (median [interquartile range]: 82.8 [20.1] vs. 51.3 [4.8] mL/100g/min, P<0.001). Cerebral blood flow was inversely associated with age, hemoglobin, and fetal hemoglobin, and correlated positively with bilirubin, and LDH, indicating that cerebral blood flow may reflect surrogates of hemolytic rate. Cerebrovascular reserve in sickle cell disease was decreased by half compared to controls (34.1 [33.4] vs. 69.5 [32.4] %, P<0.001) and was associated with hemoglobin and erythrocyte count indicating anemia-induced hemodynamic adaptations. In total, 29/36 patients (81%) and 5/11 controls (45%) had silent cerebral infarcts (median volume of 0.34 vs. 0.02 mL, P=0.03). Lesions were preferentially located in the borderzone. In conclusion, patients with sickle cell disease have a globally reduced cerebrovascular reserve as determined by arterial spin labeling with acetazolamide and reflects anemia–induced impaired vascular function in sickle cell disease. This study was registered at clinicaltrials.gov identifier 02824406.
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spelling pubmed-64429692019-04-12 Hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease Václavů, Lena Meynart, Benoit N. Mutsaerts, Henri J.M.M. Petersen, Esben Thade Majoie, Charles B.L.M. VanBavel, Ed T. Wood, John C. Nederveen, Aart J. Biemond, Bart J. Haematologica Article Sickle cell disease is characterized by chronic hemolytic anemia and vascular inflammation, which can diminish the vasodilatory capacity of the small resistance arteries, making them less adept at regulating cerebral blood flow. Autoregulation maintains adequate oxygen delivery, but when vasodilation is maximized, the low arterial oxygen content can lead to ischemia and silent cerebral infarcts. We used magnetic resonance imaging of cerebral blood flow to quantify whole-brain cerebrovascular reserve in 36 adult patients with sickle cell disease (mean age, 31.9±11.3 years) and 11 healthy controls (mean age, 37.4±15.4 years), and we used high-resolution 3D FLAIR magnetic resonance imaging to determine the prevalence of silent cerebral infarcts. Cerebrovascular reserve was calculated as the percentage change in cerebral blood flow after a hemodynamic challenge with acetazolamide. Co-registered lesion maps were used to demonstrate prevalent locations for silent cerebral infarcts. Cerebral blood flow was elevated in patients with sickle cell disease compared to controls (median [interquartile range]: 82.8 [20.1] vs. 51.3 [4.8] mL/100g/min, P<0.001). Cerebral blood flow was inversely associated with age, hemoglobin, and fetal hemoglobin, and correlated positively with bilirubin, and LDH, indicating that cerebral blood flow may reflect surrogates of hemolytic rate. Cerebrovascular reserve in sickle cell disease was decreased by half compared to controls (34.1 [33.4] vs. 69.5 [32.4] %, P<0.001) and was associated with hemoglobin and erythrocyte count indicating anemia-induced hemodynamic adaptations. In total, 29/36 patients (81%) and 5/11 controls (45%) had silent cerebral infarcts (median volume of 0.34 vs. 0.02 mL, P=0.03). Lesions were preferentially located in the borderzone. In conclusion, patients with sickle cell disease have a globally reduced cerebrovascular reserve as determined by arterial spin labeling with acetazolamide and reflects anemia–induced impaired vascular function in sickle cell disease. This study was registered at clinicaltrials.gov identifier 02824406. Ferrata Storti Foundation 2019-04 /pmc/articles/PMC6442969/ /pubmed/30523051 http://dx.doi.org/10.3324/haematol.2018.206094 Text en Copyright© 2019 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.
spellingShingle Article
Václavů, Lena
Meynart, Benoit N.
Mutsaerts, Henri J.M.M.
Petersen, Esben Thade
Majoie, Charles B.L.M.
VanBavel, Ed T.
Wood, John C.
Nederveen, Aart J.
Biemond, Bart J.
Hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease
title Hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease
title_full Hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease
title_fullStr Hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease
title_full_unstemmed Hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease
title_short Hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease
title_sort hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442969/
https://www.ncbi.nlm.nih.gov/pubmed/30523051
http://dx.doi.org/10.3324/haematol.2018.206094
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