Dynamic Cerebral Autoregulation in Homozygous Sickle Cell Disease

Kim, Yu-Sok; Nur, Erfan; Beers, Eduard J. van; Truijen, Jasper; Davis, Shyrin C.A.T.; Biemond, Bart J.; Lieshout, Johannes J. van

doi:10.1161/strokeaha.108.531996

Cited by 29 publications

(19 citation statements)

References 55 publications

(47 reference statements)

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“…14 In a previous study, we demonstrated that SCD patients also have an impaired dynamic cerebral autoregulation. 17 Together with the findings of the present study, these results imply that in SCD both mechanoregulation and chemoregulation as the 2 major operative mechanisms responsible for maintaining CBF are impaired, rendering SCD patients susceptible to ischemic episodes. Based on the highly sensitive control of the cerebral vasculature via changes in P ET CO 2 and the inverse relationship between CBF and ventilation, the alteration in CBF regulation has been proposed to contribute to breathing instability.…”

Section: Discussionsupporting

confidence: 85%

“…[14][15][16] Recently, we demonstrated that dynamic cerebral autoregulation is impaired in SCD. 17 Independent from cerebral autoregulation, the influence of the partial arterial carbon dioxide (CO 2 ) tension on CBF is of importance. Under normal conditions, increments and decrements of the partial arterial and thus end-tidal CO 2 tension (P ET CO 2 ) increase and decrease CBF by cerebral vasodilatation and vasoconstriction, respectively.…”

Section: ;114:3473-3478) Introductionmentioning

confidence: 99%

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Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

Nur

Kim

Truijen

et al. 2009

Blood

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Sickle cell disease (SCD) is associated with a high incidence of ischemic stroke. SCD is characterized by hemolytic anemia, resulting in reduced nitric oxidebioavailability, and by impaired cerebrovascular hemodynamics. Cerebrovascular CO 2 responsiveness is nitric oxide dependent and has been related to an increased stroke risk in microvascular diseases. We questioned whether cerebrovascular CO 2 responsiveness is impaired in SCD and related to hemolytic anemia. Transcranial Doppler-determined mean cerebral blood flow velocity (V mean ), near-infrared spectroscopy-determined cerebral oxygenation, and end-tidal CO 2 tension were monitored during normocapnia and hypercapnia in 23 patients and 16 control subjects. Cerebrovascular CO 2 responsiveness was quantified as ⌬% V mean and ⌬mol/L cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin per mm Hg change in end-tidal CO 2 tension. Both ways of measurements revealed lower cerebrovascular CO 2 responsiveness in SCD patients versus controls (V mean , 3.7, 3.1-4.7 vs 5.9, 4.6-6.7 ⌬% V mean per mm Hg, P < .001; oxyhemoglobin, 0.36, 0.14-0.82 vs 0.78, 0.61-1.22 ⌬mol/L per mm Hg, P ‫؍‬ .025; deoxyhemoglobin, 0.35, 0.14-0.67 vs 0.58, 0.41-0.86 ⌬mol/L per mm Hg, P ‫؍‬ .033; total-hemoglobin, 0.13, 0.02-0.18 vs 0.23, 0.13-0.38 ⌬mol/L per mm Hg, P ‫؍‬ .038). Cerebrovascular CO 2 responsiveness was not related to markers of hemolytic anemia. In SCD patients, impaired cerebrovascular CO 2 responsiveness reflects reduced cerebrovascular reserve capacity, which may play a role in pathophysiology of stroke. (Blood. 2009;114:3473-3478) IntroductionCerebral infarction is one of the most devastating complications of sickle cell disease (SCD), occurring in approximately 10% of patients in the first 2 decades of life. 1-3 Furthermore, silent cerebral infarctions occur in approximately 17% of pediatric patients 4,5 and are associated with poor educational and cognitive functioning. 6 SCD is characterized by chronic hemolytic anemia and ongoing vaso-occlusion with exacerbations often requiring medical care. [7][8][9] The vaso-occlusive process in SCD is of a complex nature mediated by red cell and leukocyte adhesion, inflammation, oxidative stress, and a hypercoagulable state, all resulting in endothelial injury and dysfunction. 8 In addition, by reducing the nitric oxide (NO) bioavailability and by damaging the endothelium through the catalyzation of oxidative reactions in endothelial cells, chronic hemolysis leads to vascular complications. [10][11][12] Elevated cerebral blood flow (CBF) velocity (Ն 200 cm/s), measured by transcranial Doppler (TCD), has been identified as a risk factor for stroke in SCD. 13 However, little is known about the mechanism of (ischemic) stroke in SCD patients, and it has not been elucidated whether the increased CBF velocity plays a causative role in stroke or whether it is a result of SCD-related hemodynamic disturbances.CBF is tightly regulated to maintain constancy of cerebral perfusion in the face of various systemic blood pressures by both ...

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Section: Discussionsupporting

confidence: 85%

Section: ;114:3473-3478) Introductionmentioning

confidence: 99%

Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

Nur

Kim

Truijen

et al. 2009

Blood

Self Cite

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“…16 Exposure to hypoxia increased the mortality rate in a mouse model of sickle cell disease, 17 suggesting that these mice are susceptible to hypoxia-induced organ failure and death. In humans, adult sickle cell patients demonstrate impairment in cerebrovascular reserve (CVR) capacity 9 and autoregulation of CBF, 18 suggesting a deficiency in cerebrovascular reactivity in the brain of these patients. Elevated cerebral CBF and reduced CVR have also been reported in the pediatric population.…”

mentioning

confidence: 99%

Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice

Cahill

Gazdzinski

Tsui

et al. 2016

J Cereb Blood Flow Metab

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Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model. Relative to age-matched controls, sickle cell anemia mice demonstrated: (1) decreased brain tissue pO 2 and increased expression of hypoxia signaling protein in the perivascular regions of the cerebral cortex; (2) elevated basal cerebral blood flow , consistent with adaptation to anemia-induced tissue hypoxia; (3) significant reduction in cerebrovascular blood flow reactivity to a hypercapnic challenge; (4) increased diameter of the carotid artery; and (5) significant volume changes in white and gray matter regions in the brain, as assessed by ex vivo magnetic resonance imaging. Collectively, these findings support the hypothesis that brain tissue hypoxia contributes to adaptive physiological and anatomic changes in Townes sickle cell mice. These findings may help define the pathophysiology for stroke in children with sickle cell anemia.

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“…However, adult patients with SCA exhibit impaired dynamic cerebral autoregulation when measuring middle cerebral artery velocity changes with postural changes. 25 Impaired cerebral autoregulation may directly contribute to small vessel ischemic disease and a decreased ability to buffer dramatic and sudden changes in blood pressure, placing patients at an increased risk for hemorrhagic stroke. 23 Patients who survive into adulthood with SCA are at risk for developing moyamoya vasculopathy, a progressive cerebrovascular vasoconstriction and development of small vessel collateral circulation.…”

Section: Neurologic Complications Of Sickle Cell Anemiamentioning

confidence: 99%

Acute Chest Syndrome of Sickle Cell Disease

Livesay

Ruppert

2012

Critical Care Nursing Quarterly

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As patients with sickle cell anemia (SCA) are living longer, health care practitioners increasingly manage the chronic effects of the disease. Although significant strides in management of children with SCA over the past decade resulted in decreased mortality, less research exists to guide the care of the adult with complications from the disease. This case study reviews the care of a young woman with SCA admitted to the hospital for vaso-occlusive crisis with subsequent acute chest syndrome and acute respiratory distress syndrome. The pathophysiology and management of SCA, vaso-occlusive crisis, and pulmonary and neurologic complications of the disease are discussed.

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Dynamic Cerebral Autoregulation in Homozygous Sickle Cell Disease

Cited by 29 publications

References 55 publications

Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice

Acute Chest Syndrome of Sickle Cell Disease

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