Regulation of Cerebral Blood Flow. Myogenic- pressure autoregulation Chemical: PaCO2, PaO2 Metabolic Neuronal

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Regulation of Cerebral Blood Flow Myogenic- pressure autoregulation Chemical: PaCO2, PaO2 Metabolic Neuronal

The Autoregulation, Stupid! Drawing of her daughter (age 7)

Flow through rigid tube

Mogens Fog Directly observed pial vessels in cats in response to various stimuli. BP: immediate vasoconstriction followed by secondary dilatation. BP: immediate vasodilatation followed by secondary constriction. Fog M. The relationship between the blood pressure and the tonic regulation of the pial arteries. J. Neurol. Psychiat. :87-97, 938. Thanks to Prof. G.Griesen, Copenhagen

Experimental data: Falling CPP. Lassen was right!

Lassen s curve by averaging large number of measurements in TBI (nearly 200 patients, monitored with TCD day-by-day)

Autoregulation of cerebral blood flow CBF [ml/min/00g] 60 40 20 2 Thanks to Dr. A Lavinio 50 CBF = CPP/R 50 Adapted from : Lang EW, Chesnut RM. Intracranial pressure. Monitoring and management. Neurosurg Clin N Am. 994 Oct;5(4):573-605. CPP [mmhg]

CBF [ml/min/00g] 60 40 20 2 50 50 CPP [mmhg] Thanks to Dr. A Lavinio

Historical block diagram illustrating general control loops for CBF Thanks to Dr.DJ Kim

General scheme of various factors controlling simultaneously CBF

Delay of autoregulation- around 0 seconds. Is it always constant?

Distribution of vascular reactivity to CO 2 9 8 7 6 5 4 3 2 2 0 600 400 700 500 6 R arterial (D) = exp((3.57)-(.)*log(d))+(.68) [%/mmhgco 2 ] Ref: Tuor '84 Ref: Levasseur '89 Ref: Wei '80(norm) Ref: Wei '80 Ref: Bouma '9 Ref: Raper '7 Ref: Lee '0 Ref: Auer '80 ---- Arterial Model 8 300 200 9 9 9 8 2 9 9 9 6 28 30 90 70 00 80 60 6 50 40 30 6 20 04 8 9 57 6 8 40 75 9 R venous (D) = 0.20*R arterial (D) [%/mmhgco 2 ] 5 20 5 30 5 40 50 70 90 60 80 00 Ref: Lee '0 ---- Venous Model 200 300 9 8 7 6 5 4 3 2 0 400 600 500 700 Thanks to Dr. S.Piechnik

Interaction between cerebral autoregulation and cerebrospinal pressure- volume compensation- potential for unstable behaviour

Clinical AUTOREGULATION assessment. What do we need? TCD, ABP and, possibly, ICP

CO2 reactivity = % change in FV / % change in CO2 Correction for changes in ABP?

Change in PaCO2 (at normal ICP and normal ABP), 0- hypocania, -normocapnia 2- hypercapnia. How primary variables react to PaCO2?

(Stroke. 998;29:968-974.) Can Cerebrovascular Reactivity Be Assessed Without Measuring Blood Pressure in Patients With Carotid Artery Disease? J. Dumville, PhD; R. B. Panerai, PhD; N. S. Lennard, MBChB; A. R. Naylor, MD; ;D. H. Evans, PhD CBF= a*etco2 +b*abp

METHODS: Static rate of autoregulation: pharmacological increase in ABP SRoR= % Change in CVR / % change in CPP

CBF Critical closing ideal AR hyper AR CBF and CVR- geometrical interpretation Insufficient AR CPP CVR SRoR< S Maximal Vasoconstriction Maximal vasodilatation SRoR= SRoR> CPP SRoR= (ΔCVR/CVR)/ (ΔCPP/CPP) CCP LLAR ULAR

ICP [mm Hg] ABP [mm Hg] CBFV [cm/s] CPP [mm Hg] CBFV [cm/s] INVERSE LASSEN CURVE? CPP [mm Hg]

Leg-cuff release (R.Aaslid et al. Stroke. 989 ;20():45-52) RoR dcvr dt CVR baseline ABP ABP baseline, Tiecks FP, Lam AM, Aaslid R, Newell DW Comparison of static and dynamic cerebral autoregulation measurements. Stroke. 995 Dec;26(2):2372-3.

Frank P. Tiecks, MD; Arthur M. Lam, MD, FRCPC; Rune Aaslid, PhD; David W. Newell, MD Comparison of Static and Dynamic Cerebral Autoregulation Measurements (Stroke. 995;26:04-09.)

The effect of the cerebral autoregulation on mean velocity (mv) was approximated by a second-order linear differential equation set with state variables x and x2, which were assumed to be equal to 0 during the control period. After the step in ABP, these equations were solved by the computer in steps of 00 milliseconds (sampling rate, f=0 Hz) by the algorithm where dp is the normalized change in mean arterial blood pressure (MABP) from its control value (cabp), including the effect of the critical closing pressure (CCP), which was assumed to be constant at 2 mm Hg in the present study. (This parameter can later be estimated individually.) MABP was obtained by filtering the pulsatile ABP at 0.5 Hz. cvmca is control velocity in the MCA. The control values were obtained as explained in "Methods." This mathematical model was characterized by three parameters: T, the time constant; D, the damping factor; and K, the autoregulatory dynamic gain.

The same ARI may be derived from slow waves of ABP and TCD Panerai R: Cardiovasc Eng (2008) 8:42 59

Gray: after hypoxia Andrew W. Subudhi,,2 Ronney B. Panerai,3 and Robert C. Roach Acute hypoxia impairs dynamic cerebral autoregulation: results from two independent techniques. J Appl Physiol. 2009 October; 07(4): 65 7.

Transient hyperaemic response test (Giller CA. Acta Neurochir (Wien). 99;08(-2):7-4)

Cross-Spectrum-Analysis between ABP and CBFV Kohärenzbedingung (COH 0.4) Thanks to Dr.C.Haubrich Phasenverschiebung M-Wellen (57.5 6.3 ) Lang EW, Diehl RR, Mehdorn HM. Cerebral autoregulation testing after aneurysmal subarachnoid hemorrhage: the phase relationship between arterial blood pressure and cerebral blood flow velocity. Crit Care Med. 200 Jan;29():58-63

Consequence of disturbed autoregulation: ischaemic insult during plateau wave of ICP

Consequence of arterial hypotension

Arterial hypotension with baseline autoregulation probably deteriorated

Lang EW, Chesnut RM. Intracranial pressure and cerebral perfusion pressure in severe head injury. New Horiz. 995 Aug;3(3):400-9

Carotid artery stenotic disease: left side impairment of reactivity, 85% of stenosis. Right side clear.

POINTS TO TAKE HOME: Several mechanisms of CBF regulation work simultaneously Pressure-autoregulation is potent brain self-protecting mechanism Autoregulation fails if CPP is too low or too high Autoregulation fails if arterial CO2 is too high Autoregulation may be tested in clinical conditions Consequences of disturbed autoregulation: Brain is exposed to ischemic insults when CPP decreases, this may reduce chance for good outcome after TBI With high CPP hyperaemia may aggravate brain oedema causing secondary rise of ICP