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Cerebral blood flow assessed with phase-contrast magnetic resonance imaging during blood pressure changes with noradrenaline and labetalol: a trial in healthy volunteers 
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.ORCID-id: 0000-0001-6331-4283
Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.ORCID-id: 0000-0001-6784-1945
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.ORCID-id: 0000-0002-2031-722X
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2024 (Engelska)Ingår i: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 140, nr 4, s. 669-678Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Adequate cerebral perfusion is central during general anesthesia. However, perfusion is not readily measured bedside. Clinicians currently rely mainly on MAP as a surrogate even though the relationship between blood pressure and cerebral blood flow is not well understood. The aim of this study was to apply phase contrast MRI to characterize blood flow responses in healthy volunteers to commonly used pharmacological agents that increase or decrease arterial blood pressure.

Methods: Eighteen healthy volunteers aged 30-50 years were investigated with phase contrast MRI. Intraarterial blood pressure monitoring was used. First, intravenous noradrenaline was administered to a target MAP of 20% above baseline. After a wash-out period, intravenous labetalol was given to a target MAP of 15% below baseline. Cerebral blood flow was measured using phase contrast MRI and defined as the sum of flow in the internal carotid arteries and vertebral arteries. CO was defined as the flow in the ascending aorta.

Baseline median cerebral blood flow was 772 ml/min (interquartile range, 674 to 871), and CO was 5,874 ml/min (5,199 to 6,355). The median dose of noradrenaline was 0.17 µg · kg−1 · h−1 (0.14 to 0.22). During noradrenaline infusion, cerebral blood flow decreased to 705 ml/min (606 to 748; P = 0.001), and CO decreased to 4,995 ml/min (4,705 to 5,635; P = 0.01). A median dose of labetalol was 120 mg (118 to 150). After labetalol boluses, cerebral blood flow was unchanged at 769 ml/min (734 to 900; P = 0.68). CO increased to 6,413 ml/min (6,056 to 7,464; P = 0.03).

Conclusion: In healthy awake subjects, increasing MAP using intravenous noradrenaline decreased cerebral blood flow and CO. This data does not support inducing hypertension with noradrenaline to increase cerebral blood flow. Cerebral blood flow was unchanged when decreasing MAP using labetalol.

Ort, förlag, år, upplaga, sidor
Wolters Kluwer, 2024. Vol. 140, nr 4, s. 669-678
Nationell ämneskategori
Neurologi Radiologi och bildbehandling Anestesi och intensivvård
Identifikatorer
URN: urn:nbn:se:umu:diva-220047DOI: 10.1097/ALN.0000000000004775PubMedID: 37756527Scopus ID: 2-s2.0-85187724522OAI: oai:DiVA.org:umu-220047DiVA, id: diva2:1831713
Forskningsfinansiär
Region VästerbottenTillgänglig från: 2024-01-26 Skapad: 2024-01-26 Senast uppdaterad: 2024-04-29Bibliografiskt granskad
Ingår i avhandling
1. Cerebral hemodynamics in stroke, cerebral small vessel disease and pharmacological interventions: a 4D flow MRI study
Öppna denna publikation i ny flik eller fönster >>Cerebral hemodynamics in stroke, cerebral small vessel disease and pharmacological interventions: a 4D flow MRI study
2024 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Alternativ titel[sv]
Cerebral hemodynamik vid stroke, cerebral småkärlssjukdom och farmakologiska interventioner : en 4D flow MRI-studie
Abstract [en]

Background and aim: Current cerebrovascular imaging techniques provide important information on arterial anatomy and structural pathologies, such as stenoses and occlusions, but physicians are left to infer how the blood flow is affected. In addition, the relationship between blood pressure and cerebral blood flow is complex and poorly understood. Increased transmission of cardiac pulsatility to the cerebral microvasculature has been suggested as a causative factor of cerebral small vessel disease (CSVD) but previous research have yielded conflicting results regarding this relationship. 4D flow magnetic resonance imaging (MRI) is a novel and promising technique enabling time-resolved blood flow quantification with whole-brain coverage and relatively short scan times. However, despite its obvious potential, there is not yet an evidence-based application for the use of 4D flow MRI within stroke or CSVD. This dissertation aimed to apply 4D flow MRI to describe blood flow patterns in posterior circulation stroke and cerebral blood flow responses to common pharmacological agents used to alter arterial blood pressure as well as to examine the relationship between cerebral arterial pulsatility and CSVD.

Methods and Results: This doctoral dissertation consisted of four papers, referred to by roman numerals. 4D flow MRI and computed tomography angiography (CTA) were applied in 25 patients with acute ischemic stroke in the posterior circulation and a reference population of 15 healthy elderly (paper I). Individual flow profiles were created for each stroke patient and hemodynamic disturbances as well as collateral compensation were described. We show that hemodynamic findings were related to structural findings from CTA.

The cross-sectional relationship between cerebral arterial pulsatility (quantified using 4D flow MRI as pulsatility index [PI] and flow volume pulsatility [FVP]) and features of CSVD were examined using regression analysis in 89 patients with acute ischemic stroke (paper II) and a population-based sample of 862 elderly (paper III). Internal carotid artery FVP was associated with increasing white matter hyperintensity (WMH) volume in patients with stroke and TIA (paper II). In addition, increasing middle cerebral artery FVP and PI were associated with worse cognitive function. In the population sample, high FVP and PI were associated with increasing WMH volume, lower brain volume and the presence of lacunes, but not the composite MRI-CSVD (paper III). Among subjects with MRI-CSVD, displaying symptoms consistent with cerebral small vessel disease was associated with higher WMH volume, lower brain volume and active smoking, but not any measure of pulsatility.

Eighteen healthy volunteers were administered noradrenaline to increase mean arterial pressure by 20% above baseline, and labetalol to decrease mean arterial pressure to 15% below baseline (paper IV). Cerebral blood flow was measured using phase-contrast MRI at each blood pressure level and compared to baseline. Despite a marked increase in blood pressure, noradrenaline administration caused a reduction in cerebral blood flow and cardiac output. Meanwhile, labetalol administration caused no change in cerebral blood flow but an increased cardiac output.

Conclusions: 4D flow MRI can detect hemodynamic disturbances and discriminate between hemodynamic disturbances and normal flow in patients with structural vascular pathologies. This additional information compared to structural imaging alone could potentially be used for prognosis and selection for procedures in clinical care. Cerebral arterial pulsatility is modestly associated with several MRI and clinical features of CSVD but not all. Cerebral arterial pulsatility as the main risk factor of CSVD seems unlikely but its involvement in the pathophysiology cannot be ruled out. Raising the blood pressure with noradrenaline decreases cerebral blood flow and cardiac output without any redistribution from peripheral to cerebral flow. This highlights the pitfalls of using blood pressure as a surrogate for cerebral blood flow and questions the validity of our understanding of cerebral autoregulation. Lowering the blood pressure with labetalol does not affect cerebral blood flow, reassuring its use in clinical routine. 4D flow MRI can be integrated into an in-patient work-up in selected cases of acute ischemic stroke and into the workflow of large epidemiological studies.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå University, 2024. s. 79
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 2304
Nyckelord
4D flow MRI, cerebral blood flow, cerebral arterial pulsatility, pulsatility index, stroke, cerebral small vessel disease, noradrenaline, labetalol, white matter hyperintensities, lacunes, perivascular spaces
Nationell ämneskategori
Neurologi
Forskningsämne
neurologi
Identifikatorer
urn:nbn:se:umu:diva-223865 (URN)978-91-8070-391-8 (ISBN)978-91-8070-392-5 (ISBN)
Disputation
2024-05-31, Betula, målpunkt L0, byggnad 6M, Norrlands universitetssjukhus, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2024-05-08 Skapad: 2024-04-29 Senast uppdaterad: 2024-04-30Bibliografiskt granskad

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Birnefeld, JohanWåhlin, AndersEklund, AndersQvarlander, SaraHaney, MichaelMalm, JanZarrinkoob, Laleh

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NeurovetenskaperAnestesiologi och intensivvårdUmeå centrum för funktionell hjärnavbildning (UFBI)Centrum för medicinsk teknik och fysik (CMTF)Institutionen för tillämpad fysik och elektronikInstitutionen för strålningsvetenskaper
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