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

Lena Václavů, Benoit N. Meynart, Henri J. M. M. Mutsaerts, Esben Thade Petersen, Charles B. L. M. Majoie, Ed T. VanBavel, John C. Wood, Aart J. Nederveen, Bart J. Biemond

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)690-699
JournalHaematologica
Volume104
Issue number4
Early online date6 Dec 2018
DOIs
Publication statusPublished - 2019

Cite this

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. In: Haematologica. 2019 ; Vol. 104, No. 4. pp. 690-699.
@article{d5b2e3ca66b345c99f3088211771ae7c,
title = "Hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease",
abstract = "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.",
author = "Lena V{\'a}clavů and Meynart, {Benoit N.} and Mutsaerts, {Henri J. M. M.} and Petersen, {Esben Thade} and Majoie, {Charles B. L. M.} and VanBavel, {Ed T.} and Wood, {John C.} and Nederveen, {Aart J.} and Biemond, {Bart J.}",
note = "Copyright {\circledC} 2018, Ferrata Storti Foundation.",
year = "2019",
doi = "10.3324/haematol.2018.206094",
language = "English",
volume = "104",
pages = "690--699",
journal = "Haematologica",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "4",

}

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.

In: Haematologica, Vol. 104, No. 4, 2019, p. 690-699.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease

AU - Václavů, Lena

AU - Meynart, Benoit N.

AU - Mutsaerts, Henri J. M. M.

AU - Petersen, Esben Thade

AU - Majoie, Charles B. L. M.

AU - VanBavel, Ed T.

AU - Wood, John C.

AU - Nederveen, Aart J.

AU - Biemond, Bart J.

N1 - Copyright © 2018, Ferrata Storti Foundation.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85064004719&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30523051

U2 - 10.3324/haematol.2018.206094

DO - 10.3324/haematol.2018.206094

M3 - Article

VL - 104

SP - 690

EP - 699

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 4

ER -