Integrative Human Cardiovascular Control The Panum Institute/ - - PowerPoint PPT Presentation

Integrative Human Cardiovascular Control

The Panum Institute/ Rigshospitalet, University of Copenhagen 2019

Cerebral blood flow and oxygenation, static and dynamic autoregulation, and relation to orthostatic stress

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ABP (mmHg)

50 100 150

Time (s) 20 40 60 SV (%)

50 100

Valsalva

• Pott. JAP 2003

Beat-to-beat SV: Ultrasound Doppler (bold) and Modelflow (thin)

5/14/2019

Valsalva maneuver

Valsalva maneuver

Wieling W, Van Lieshout JJ. Clin Auton Res 2002

The ‘fainting lark’

Combining the effects of a) acute arterial hypotension by gravity and b) raised intrathoracic pressure with c) cerebral vasoconstriction in response to hypocapnia

Outline of Presentation – Measurement and Regulation of Cerebral Blood Flow

• Techniques and Methodological Issues
• What determines Brain Blood Flow?
• Static and Dynamic Cerebral Autoregulation and beyond

Cerebral Blood Flow (CBF) and Imaging Techniques

• Global CBF (arterial-venous diff N2O, 133Xe, O2)
• Magnetic Resonance Imaging (MRI)
• MRA (Magnetic Resonance Angiography & Venography)
• Regional CBF (Ultrasound - Transcranial Doppler)
• Single-Photon Emission Computed Tomography (SPECT)
• Positron Emission Tomography (PET)
• SPECT/CT and PET/CT, Near-Infrared Spectroscopy

Kety and Schmidt, J Clin Invest 1948

Measurement of Global Cerebral Circulation - Inert Gas Nitrous Oxide

• Systemic circulation:

VO2 = CO * (Ca – Cv)

• Cerebral circulation: CMRO2 = CBF * (Ca – Cv jug)

Fick Principle

CPP = CBF * CVR

Cerebral Perfusion Pressure Cerebral Blood Flow Cerebral Vascular Resistance

voltage (V) = amperage (I) * resistance (R)

Ohm’s Law

MAP = CBFV * CVR

Mean Arterial Pressure Cerebral Blood Flow Velocity Cerebral Vascular Resistance at brain level

Applied to TransCranial Doppler Ultrasonography

Transcranial Doppler Cerebral Blood Flow Velocity

• TCD middle cerebral artery blood velocity

pro: - beat-to-beat evaluation of (regional) CBF con: - larger changes in arterial distending pressure may affect MCA diameter with under / overestimation of CBF

• heterogeneity in cerebral vascular responsiveness

Assessment of Cerebral Perfusion

• transcranial Doppler cerebral artery velocity

is taken as 'a surrogate' for CBF

• cerebral blood flow/velocity is the outcome measure,

and a relationship to vascular control is only inferred

• arterial pressure may not fully reflect CPP (the pressure

driving CBF in the large cerebral arteries)

Limitations

Constant diameter under the conditions of the study?

?

Reviewer’s comment:

Sympathetic activation by handgrip exercise reduces MCA cross-sectional area

7T MRI evaluation of Middle Cerebral Artery during Rhythmic Handgrip Exercise

▪

Effects of exercise on cerebral metabolism are highly heterogeneous

▪

Increases in CBF are not global but localized to specific areas of the brain

Brain vascular control during exercise

• arterial pressure may not fully reflect the pressure

driving CBF in the large cerebral arteries

• transcranial Doppler cerebral artery velocity

is taken as 'a surrogate' for CBF

• cerebral blood flow/velocity is the outcome measure,

and a relationship to vascular control is only inferred

Limitations to be considered

Outline of Presentation – Measurement and Regulation of Cerebral Blood Flow

• Techniques and Methodological Issues
• What determines Brain Blood Flow?

• brain activation (visual stimulation, exercise)
• metabolic (from rest to exercise)
• chemical - PaCO2, O2
• autoregulation
• neurogenic - sympathetic system influence
• endothelial cell  smooth muscle cell
• ATP, adenosine, brain-derived neurotrophic factor (BDNF)
• cardiac output
• ageing
• Which influences for brain blood flow?

Control of Cerebral Circulation in Health and Disease

• CHEMICAL (PaCO2, PaO2)

BP (mm Hg)

MCAV (cm·s

• 1)

Time (s)

PETCO2 (mm Hg)

Cerebral Responsiveness to Carbon Dioxide (CO2 reactivity of the brain)

• Activation

Ingvar DH. Functional landscapes of the dominant hemisphere. Brain Res 1976

❖

Activation of the brain by exercise enhances CBF

Cerebral blood flow during exercise in T2DM

• Humans. J Appl Physiol. 1992;72:1123-1132
• Changes in MCA Vmean during exercise are similar to

those recorded with the initial slope index of the 133Xe clearance method

• During heavy dynamic exercise, MCA Vmean

increases 24 (10-47)%

Effects of exercise intensity and duration on indices of cerebral blood flow and oxygenation during exercise

Reductions in Q accomplished by lower body negative pressure (LBNP), increases in Q by infusions of 25% human serum albumin

Relationship cardiac output and MCA V from rest to exercise

Effects of Exercise on CBF in Heart Failure

• With one-legged exercise CBFV is maintained but

declines with two-legged exercise

• AGEING

~15% reduction in gray matter flow between the 3rd and 5th decade

Shaw TG, Mortel KF, Meyer JS, Rogers RL, Hardenberg J, Cutaia MM. Cerebral blood flow changes in benign aging and cerebrovascular disease. Neurology 1984 Meyer JS, Terayama Y, Takashima S. Cerebral circulation in the elderly. Cerebrovasc Brain Metab Rev 1993

• BODY POSITION

Bode H. Eur J Pediatr 1991 Levine BD, et al. Circulation 1994 Bondar RL, et al. Stroke 1995 Schondorf R, et al. Stroke 1997 Novak V, et al. Stroke 1998 Lipsitz LA, et al. Stroke 2000 Van Lieshout JJ, et al. Stroke 2001 Harms MPM, et al. Stroke 2000 Pott F, et al. JAP 2000 Alperin N, et al. J. Magn Reson Imaging 2005

• Assumption of the upright position

carries the head above heart level  BP at brain level ~ 20 mmHg   Cardiac output 20-30%   PCO2   Cerebral Blood Velocity 15%  Brain takes 15-20% of cardiac output

Postural reduction in central blood volume affects the brain

Middle cerebral artery blood velocity declines when standing

Time (s) 30 60 MAP

50 100 150

MCA Vmean

(cm.s

• 1)

50 100 Standing

Outline of Presentation – Measurement and Regulation of Cerebral Blood Flow

• Techniques and Methodological Issues
• What determines Brain Blood Flow?
• Static and Dynamic Cerebral Autoregulation

Time (s)

1 2 3 4 5 6 7 8 9 10

 Blood Pressure (%)

90 100 110 120 130

 MCAV (%)

90 100 110 120 130

Cerebral Autoregulation in Healthy Subjects

Effect of Dynamic Exercise on Blood Pressure

What will brain blood flow do?

… and on Cerebral Blood Velocity

autoregulation malfunction ?

Static CA

reflects the overall efficiency of the system

Static and Dynamic Components of Cerebral Autoregulation (CA)

Q

Dynamic CA

ability to restore cerebral blood flow within seconds in response to BP changes reflects latency of regulatory system

P

Perfusion Pressure mmHg 60 150 Perfusion Pressure mmHg CBF CVRI Cerebral vasoconstriction Cerebral vasodilation 60 150

Cerebral Autoregulation

Courtesy of Eubank and Raven

In biological systems reflex gain is not infinite

• Inducing a fall in mean arterial pressure (cuff release;

Aaslid manoeuvre)

• Rest and steady-state orthostatic stress

Spontaneous and induced oscillations

Dynamic Cerebral Autoregulation - Assessment

Cerebrovascular autoregulation

Cerebrovascular adaptation following release of muscle ischemia

ABP to CBFV transfer described in terms of phase and gain

Transfer of Spontaneous Oscillations in Blood Pressure to Cerebral Blood Velocity

Dynamic Cerebral Autoregulation - Phase Difference

CBFV BP

Dynamic Cerebral Autoregulation - Gain

CBFV BP

Determination of delay between BP and CBFv

BP CBFv

= MCA Vmean = MAPbrain 0.067 Hz 0.100 Hz 0.167 Hz Phase 50°, Gain 0.33 Phase 119°, Gain 0.53 Phase 77°, Gain 0.33

Normal Dynamic Cerebral Autoregulation

Reduced Dynamic Cerebral Autoregulatory Efficacy in Uncomplicated T2DM

Time (s)

1 2 3 4 5 6 7 8 9 10

 Blood Pressure (%)

90 100 110 120 130

 MCAV (%)

90 100 110 120 130

Cerebral Autoregulation – Controls vs. Acute Ischemic Stroke (MCA Territory)

Time (s)

1 2 3 4 5 6 7 8 9 10

 Blood Pressure (%)

90 100 110 120 130

 MCAV (%)

90 100 110 120 130

• NEUROGENIC – SYMPATHETIC INFLUENCE

▪ role of sympathetic activation for CBF controversial ▪ dense sympathetic innervation middle size brain arteries ▪ sympathetic innervation of larger cerebral arteries ▪ NE “spillover” from brain vasculature in healthy humans

but not in patients with autonomic failure

▪ sympathetic activation reduces MCA cross-sectional area

Sympathetic effects on CBF during exercise

Control of Cerebral Circulation in Health and Disease

Coupling of synaptic activity with substrate utilization (neurovascular coupling)

Summing up ...

❖ Postural decline in cerebral perfusion/oxygenation -

no infinite gain in CA capacity

❖ Influence of cardiac output on cerebral perfusion

independent from arterial pressure

❖ CBF measurement techniques have limitations ❖ Heterogeneity in cerebral vascular responsiveness

and probably in dynamic autoregulatory capacity

• We describe the restoration and maintenance of

microcirculation and molecular and cellular functions of the intact pig brain under ex-vivo normothermic conditions up to four hours post-mortem

• The isolated, intact large mammalian brain possesses

an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval

Cerebral perfusion pressure = BP at brain level minus critical closing pressure (CrCP)

Cerebral perfusion pressure = BP at brain level minus critical closing pressure (CrCP) CrCP: the pressure inside a blood vessel below which the vessel will collapse and blood flow ceases

Cerebral perfusion pressure = BP at brain level minus critical closing pressure (CrCP) CrCP: the pressure inside a blood vessel below which the vessel will collapse and blood flow ceases CrCP calculated as the instantaneous relationship between first harmonic filtered BPbrain and CBFv waveforms

Effects of Body Position on the (a-ET)PCO2 gradient

PET,CO2 (mmHg)

30 40 50

*****************************

MCA Vmean (cm·s-1)

45 60 75

***

Time (s)

• 60

60 120 180 240 300

MAP (mmHg)

50 75 100

Contribution of CO2 on the postural restraint in cerebral perfusion is TRANSIENT

• spontaneous breathing

○ isocapnic tilt

Rembrandt van Rijn (~1624) – The unconscious patient (‘Allegory of Smell’)

Define the medical error

Quiz II