Incomplete recovery of cerebral blood flow dynamics in sufficiently treated high blood pressure

Martin Müller, Mareike Österreich, Alexander von Hessling, Roy S Smith, Martin Müller, Mareike Österreich, Alexander von Hessling, Roy S Smith

Abstract

Objective: Whether cerebrovascular regulation is different in patients with controlled high blood pressure (HBP) with and without small vessel disease (SVD).

Methods: Sixty-seven healthy controls (mean age ± SD, 45 ± 16 years; 30 women, 37 men) and 40 patients (mean age, 64 ± 13 years; 14 women, 26 men) with HBP and different stages of SVD, underwent simultaneous recordings of the spontaneous fluctuations of BP, blood flow velocity (CBFV) in both middle cerebral arteries (MCA), and of end-tidal CO2 (ETCO2). Coherence and transfer function gain and phase between BP and CBFV were assessed in the frequency ranges of VLF (0.02-0.07 Hz), low frequency (0.07-0.15), and high frequency (>0.15). BP SD indicated BP variability (BPV).

Results: In controls (BP, 86 ± 13 mmHg; ETCO2, 39 ± 4 mmHg; BPV, 15 ± 6 mmHg), gain, phase and coherence were not age-dependent in simple or a multiple regression models. BPV correlated significantly in both MCAs with gain in low frequency and high frequency, and with phase in VLF and high frequency. In patients (BP, 91 ± 16 mmHg, ETCO2, 39 ± 4 mmHg, BPV 18 ± 5 mmHg), only gain showed some differences between different SVD groups. Comparing all patients with 25 controls of similar age and sex, patients exhibited significantly (P < 0.05-P < 0.005): increased coherence and gain in VLF, decreased phase in VLF and low frequency, correlations between BPV with phase in low frequency (left) and with gain in VLF (left) and in high frequency (left and right).

Conclusion: Phase seems an age independent autoregulatory index. In controlled HBP, CBF regulation is degraded at longlasting CBF changes; BPV effects lose their physiological bilateral distribution.

References

    1. Frahm-Falkenberg S, Ibsen R, Kjellberg J, Jennum P. Health, social and economic consequenes of dementias: a comparative national cohort study. Eur J Neurol 2016; 23:1400–1407.
    1. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010; 9:689–701.
    1. Tan R, Traylor M, Rutten-Jacobs L, Markus H. New insights into mechanisms of small vessel disease stroke from genetics. Clin Sci (Lond) 2017; 131:515–531.
    1. Neurology Working Group of the Cohorts for Heart, Aging Research in Genomic Epidemiology (CHARGE) Consortium, the Stroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC). Identification of additional risk loci for stroke and small vessel disease: a meta-analysis of genome-wide association studies. Lancet Neurol 2016; 15:695–707.
    1. Mancia G, Bombelli M, Facchetti R, Madotto F, Corrao G, Trevano FQ, et al. Long-term prognostic value of blood pressure variability. Hypertension 2007; 49:1265–1270.
    1. Umemoto S, Ogihara T, Matsuzaki M, Rakugi H, Ohashi Y, Saruta T. Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial Group. Effects of calcium channel blocker-based combinations on intra-individual blood pressure variability: post hoc analysis of the COPE trial. Hypertens Res 2016; 39:46–53.
    1. Yperzeele L, van Hooff RJ, Nagels G, De Smedt A, De Keyser J, Brouns R. Heart rate variability and baroreceptor sensitivity in acute stroke: a systematic review. Int J Stroke 2015; 10:796–800.
    1. Mitchell GF, Hwang SJ, Vasan RS, Larson MG, Pencina MJ, Hamburg NM, et al. Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation 2010; 121:505–511.
    1. Shi Y, Thrippleton MJ, Makin SD, Marshall I, Geerlings MI, de Craen AJ, et al. Cerebral blood flow in small vessel disease: a systematic review and meta-analysis. J Cereb Blood Flow Metab 2016; 36:1653–1667.
    1. Duncombe J, Kitamura A, Hase Y, Ihara M, Kalaria RN, Horsburgh K. Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia. Clin Sci (Lond) 2017; 131:2451–2468.
    1. Jespersen SN, Østergaard L. The roles of cerebral blood flow, capillary transit time heterogeneity, and oxygen tension in brain oxygenation and metabolism. Jl Cereb Blood Flow Metab 2012; 32:264–277.
    1. Arba F, Mair G, Carpenter T, Sakka E, Sandercock PAG, Lindley RI. IST-3 Trial Collaborators. Cerebral white matter hypoperfusion increases with small-vessel disease burden. Data From the Third International Stroke Trial. J Stroke Cerebrovasc Dis 2017; 26:1506–1513.
    1. Huynh TJ, Murphy B, Pettersen JA, Tu H, Sahlas DJ, Zhang L, et al. CT perfusion quantification of small-vessel ischemic severity. AJNR Am J Neuroradiol 2008; 29:1831–1836.
    1. Serrador JM, Sorond FA, Vyas M, Gagnon M, Iloputaife ID, Lipsitz LA. Cerebral pressure-flow relations in hypertensive elderly humans: transfer gain in different frequency domains. J Appl Physiol (1985) 2005; 98:151–159.
    1. Birns J, Jarosz J, Markus HS, Kalra L. Cerebrovascular reactivity and dynamic autoregulation in ischaemic subcortical white matter disease. J Neurol Neurosurg Psychiatry 2009; 80:1093–1098.
    1. Zhang R, Zuckerman JH, Giller CA, Levine BD. Transfer function analysis of dynamic cerebral autoregulation in humans. Am J Physiol 1998; 274 (1 Pt 2):H233–H241.
    1. Meel-van den Abeelen ASS, Simpson D, Zhang R, Tarumi T, Rickards CA, Payne S, et al. Between-center variability in transfer function analysis: a widely used method for linear quantification of the dynamic pressure-flow relation: the CARnet bootstrap study. Med Biol Eng 2014; 36:620–627.
    1. Claassen JA, Meel-van den Abeelen AS, Simpson DM, Panerai RB. international Cerebral Autoregulation Research Network (CARNet). Transfer function analysis of dynamic cerebral autoregulation: a white paper from the International Cerebral Autoregulation Research Network. J Cereb Blood Flow Metab 2016; 36:665–680.
    1. Müller M, Österreich M, Müller A, Lygeros L. Assessment of the brain's macro- and micro-circulatory blood flow responses to CO2 via transfer function analysis. Front Physiol 2016; 7:162.
    1. Zhang R, Behbehani K, Levine BD. Dynamic pressure–flow relationship of the cerebral circulation during acute increase in arterial pressure. J Physiol 2009; 587 (Pt 11):2567–2577.
    1. Fazekas F, Barkhof F, Wahlund LO, Pantoni L, Erkinjuntti T, Scheltens P, et al. CT and MRI rating of white matter lesions. Cerebrovasc Dis 2002; 13 133 Suppl 2:31–36.
    1. Ortega-Gutierrez S, Petersen N, Masurkar A, Reccius A, Huang A, Li M, et al. Reliability, asymmetry and age influence on dynamic cerebral autoregulation measured by spontaneous fluctuations of blood pressure and cerebral blood flow velocities in healthy individuals. J Neuroimaging 2014; 24:379–386.
    1. Xing C-Y, Tarumi T, Meijers RL, Turner M, Repshas J, Xiong L, et al. Arterial pressure, heart rate, and cerebral hemodynamics across the adult life pan. Hypertension 2017; 69:712–720.
    1. Liu J, Simpson DM, Allen R. High spontaneous fluctuation in arterial blood pressure improves the assessment of cerebral autoregulation. Physiol Meas 2005; 26:725–741.
    1. Claassen JAHR, Levine BD, Zhang R. Dynamic cerebral autoregulation during repeated squat-stand maneuvers. J Appl Physiol (1985) 2009; 106:153–160.
    1. Katsogridakis E, Simpson DM, Bush G, Fan L, Birch AA, Allen R, et al. Revisiting the frequency domain: the multiple and partial coherence of cerebral blood flow velocity in the assessment of dynamic cerebral autoregulation. Physiol Meas 2016; 37:1056–1073.
    1. Mahdi A, Nicolic D, Birch AA, Olufsen MS, Panerai RB, Simpson DM, et al. Increased blood pressure variability upon standing up improves reproducibility of cerebral autoregulation indices. Med Eng Phys 2017; 47:151–158.
    1. Barnes SC, Ball N, Panerai RB, Robinson TG, Haunton VJ. Random squat/stand maneuvers: a novel approach for assessment of dynamic cerebral autoregulation? J Appl Physiol (1985) 2017; 123:558–566.
    1. Elting JW, Aries MJ, van der Hoeven JH, Vroomen PC, Maurits NM. Reproducibility and variability of dynamic cerebral autoregulation during passive cyclic leg raising. Med Eng Phys 2014; 36:585–591.
    1. Smirl JD, Hoffman K, Tzeng YC, Hansen A, Ainslie PN. Methodological comparison of active- and passive-driven oscillations in blood pressure; implications for the assessment of cerebral pressure-flow relationships. J Appl Physiol (1985) 2015; 119:487–501.
    1. Ogawa Y, Aoki K, Kato J, Iwasaki K-I. Differential effects of mild central hypovolemia with furosemide administration vs lower body suction on dynamic cerebral autoregulation. J Appl Physiol 2013; 114:211–216.
    1. Purkayastha S, Fadar O, Mehregan A, Salat DH, Moscufo N, Meier DS, et al. Impaired cerebrovascular hemodynamics are associated with cerebral white matter damage. J Cereb Blood Flow Metab 2014; 34:228–234.
    1. Lipsitz LA, Mukai S, Hammer J, Gagnon M, Babikian V. Dynamic regulation of middle cerebral artery blood flow velocity in aging and hypertension. Stroke 2000; 31:1897–1903.
    1. Zhang R, Witkowski S, Fu Q, Claassen JAHR, Levine BD. Cerebral hemodynamics after short- and long-term reduction in blood pressure in mild and moderate hypertension. Hypertension 2007; 49:1149–1155.
    1. Tzeng YC, MacRae BA. Interindividual relationships between blood pressure and cerebral blood flow variability with intact and blunted cerebrovascular control. J Appl Physiol 2013; 114:888–895.
    1. Aaslid R, Blaha M, Sviri G, Douville CM, Newell DW. Asymmetric dynamic cerebral autoregulatory response to cyclic stimuli. Stroke 2007; 38:1465–1469.
    1. Merkelbach S, Müller M, Huber G, Schimrigk K. Alteration of cerebral blood flow in patients with bacterial and biral Meningoencephalitis. AJNR Am J Neuroradiol 1998; 19:433–438.
    1. Lobaugh NJ, Caldwell CB, Black SE, Leibovitch FS, Swartz RH. Three brain SPECT Region-of-Interest templates in elderly people: normative values, hemispheric asymmetries, and a comparison of single- and multihead cameras. J NucI Med 2000; 41:45–56.
    1. Lang EW, Yip K, Griffith J, Lagopoulos J, Mudaliar Y, Dorsch NW. Hemispheric asymmetry and temporal profiles of cerebral pressure autoregulation in head injury. J Clin Neurosci 2003; 10:670–673.
    1. Nishimura Y, Ito T, Saavedra JM. Angiotensin II AT1 blockade normalizes cerebrovascular autoregulation and reduces cerebral ischemia in spontaneously hypertensive rats. Stroke 2000; 31:2478–2486.
    1. Sigurdsson ST, Paulson OB, Nielsen AH, Newell DWl. Bradykinin antagonist counteracts the acute effect of both angiotensin-converting enzyme inhibition and of angiotensin receptor blockade on the lower limit of autoregulation of cerebral blood flow. J Cereb Bood Flow Metab 2014; 34:467–471.
    1. Hamner JW, Tan CO. Relative contributions of sympathetic, cholinergic, and myogenic mechanisms to cerebral autoregulation. Stroke 2014; 45:1771–1777.
    1. Tzeng Y-U, Chan GSH, Willie CK, Ainslie PN. Determinants of human cerebral pressure–flow velocity relationships: new insights from vascular modelling and Ca2+ channel blockade. J Physiol 2011; 589:3263–3274.

Source: PubMed

Подписаться