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THE AUSTRALIAN NATIONAL UNIVERSITY. Special Circulations Christian Stricker Associate Professor for Systems Physiology ANUMS/JCSMR - ANU Christian.Stricker@anu.edu.au http:/ /stricker.jcsmr.anu.edu.au/Specirc.pptx. Aims. The students should

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THE AUSTRALIAN NATIONAL UNIVERSITY

Special CirculationsChristian StrickerAssociate Professor for Systems PhysiologyANUMS/JCSMR - ANUChristian.Stricker@anu.edu.auhttp://stricker.jcsmr.anu.edu.au/Specirc.pptx

slide3
Aims

The students should

  • realise that different vascular beds utilise different mechanisms for regulation of blood flow;
  • understand why coronary flow is largely during diastole;
  • be familiar with mechanisms resulting in coronary vaso-dilation as a consequence of increased cardiac work;
  • recognise why subendocardial vessels are prone to ischaemic damage;
  • be cognisant of factors regulating cerebral blood flow including autoregulation; and
  • know why cerebral vessels are different to many other vessels.
contents
Contents
  • Coronary arteries
    • Anatomy
    • Pressures in LCA and RCA
    • Autoregulation of perfusion
    • Metabolic factors determining perfusion
    • Substrate utilisation
    • Stenosis and flow
  • Cerebral vessels
    • Anatomy
    • Autoregulation
    • Metabolic factors determining perfusion
coronary arteries
Coronary Arteries

Modified from Boron & Boulpaep(2009), 2nd ed.

Despopoulos & Silbernagl2003, 5th ed.

  • Coronary arteries originate from aorta, behind valve cusps.
  • In general RCA (~1/7 of total): RV and RA; LCA: LV and LA.
  • Collateral network gives rise to high density of capillaries.
  • Veins drain into coronary sinus; from septum directly into ventricles (Thebesian veins → physiological shunt; see later).
coronary blood flow
Coronary Blood Flow
  • LCA: Flow drops to ≤ 0 at start of isovolumetric phase. Maximal flow during early diastole: LV/A perfused largely “only” during diastole.
  • RCA: Flow variable and maintained. Maximal flow at end of fast ejection part: RV/A perfused during systole & diastole.
  • Phasic blood flow: varies with cardiac cycle.
  • LV is much more critical in its blood supply than RV:
    • Flow in LCA larger than that in RCA (~ 6 - 7 x).

Modified from Boron & Boulpaep(2009), 2. ed.

wall tension perfusion
Wall Tension & Perfusion

Patton et al. (1989), 21. ed.

Despopoulos & Silbernagl2003, 5th ed.

  • Mechanical compression of LCA (transmural): dependent on wall position.
    • Subepicardial vessels little affected: better perfusion.
    • Subendocardialvessels compressed during systole: flow stops temporarily – i.e. flow limited during systole → these vessel beds are prone to hypoxia.
  • Systolic perfusion of RCA possible due to smaller cavity pressure (25 torr; limited “squeeze” on vessels).
autoregulation of perfusion
Autoregulation of Perfusion
  • Immediate response.
  • Blood flow ± constant over pressure range between 60 – 180 torr.
  • Change in arteriolar resistance: pre-capillary sphincters.
  • Mechanism(s) (?):
    • myogenic: most likely
    • metabolic: ?
    • neuronal: works without.
  • Below autoregulation range, flow is dependent on resistance.

Berne & Levy, 2008, 6. ed.

neural control of perfusion
Neural Control of Perfusion
  • Ventricular fibrillation → removal of transmuraltension → blood flow↑→ ↑.
    • Over time, R↑ (autoregulation): flow↓ → homeostatic response.
  • Stimulation of sympathetic ganglion (stellate): R↑ initially
    • α1 receptors: constriction; but
    • compensated via R↓ later (metabolic hyperaemia, slow).
  • Metabolic self-regulation more powerful than neuronal response.

Berne & Levy, 2008, 6. ed.

cardiac work blood flow
Cardiac Work & Blood Flow
  • Cardiac work linearly increases blood flow.
  • Same result if heart is denervated (minimal role of neuronal control; allows for transplantation).
  • Myocardial O2 balance:
    • O2 blood content & blood flow

against

    • metabolic demand:
      • if quotient ↓: vasodilation.
      • if quotient ↑: vasoconstriction.
  • What are molecular mechansims?

Berne & Levy, 2008, 6. ed.

modulation of coronary resistance
Modulation of Coronary Resistance

Berne & Levy, 2008, 6. ed.

  • Autonomic control minimal.
  • Metabolic control via KATP, NO, adenosine, H+, K+, and .
key metabolic factors
Key Metabolic Factors
  • ATP (energy availablility) via KATP channels
    • ATP production↓ activates KATP channels.
    • When activated, KATP hyperpolarises VSMC → Ca2+ influx↓→ vasodilation.
    • KATPchannels also activated on cardiomyocytes→ AP width↓ → Ca2+ entry↓→ limits energy expenditure.
  • Adenosine
    • transiently released from myocardial cells (short effect).
    • activates adenosine receptors and also activates KATP channels → vasodilation.
    • enhances release of NO → vasodilation.
  • NO (nitrous oxide; from endothelial cells)
    • relaxes smooth muscle cells.
substrate utilisation
Substrate Utilisation

Despopoulos & Silbernagl2003, 5. ed.

  • At rest, glucose, fatty acids and lactate serve equally to provide energy.
  • During exercise, lactate from muscle is increasingly important in energy production.
  • Most increase via perfusion↑. But O2 consumption↑ slightly more than perfusion↑: O2 extraction↑ (but only little).
coronary stenosis and flow
Coronary Stenosis and Flow
  • O2 extraction is close to maximal → flow limited.
  • Narrowing >~80% only causes significant flow↓ at rest.
    • Accentuated under exercise (exercise testing).
  • Effect of stenosis: P↓ & autoregulation↓ → flow↓.
    • Compensatory vasodilation in post-stenotic bed.
    • Acute consequence: hypoxia/ischaemia (infarct).
    • Chronic consequence: build-up of cap. collaterals.

Patton et al. (1989), 21. ed.

vasomotion and stenosis
Vasomotion and Stenosis
  • Atherosclerotic plaques hinder vasomotion.
  • Vasodilation→R↓in each vascular arm→ flow↑ in healthy vascular beds.
  • However, as R = const.around sclerotic plaques, relative R↑ locally → flow↓over plaque:haemodynamic steal.
    • Risk in exercise testing.
cerebral circulation

Cerebral Circulation

Cerebral blood flow (CBF)

Brain is the least tolerant organ to hypoxaemia/ischaemia.

cerebral vessels
Cerebral Vessels
  • Total flow: 15% of CO for an organ that is 2% of BW.
  • Largest flow via carotid art.
  • Collateral paths via circle of Willis.
    • Direction of flow can change under pathological conditions.
  • Fixed volume (cranium) → tight volume control.
  • Autonomic nervous fibres accompany vessels into the cranium.

Modified from Boron & Boulpaep(2009), 2. ed.

neural control of cbf
Neural Control of CBF
  • Sympathetic: constriction (cervical sympath. fibres; α1-effect)
  • Parasympathetic: dilation via greater superf. petrosal nerve (VII); dense net around cerebral arteries (see above; black deposits stain acetylcholinesterase).
  • Neuronal control exists, but its functional impact under normal condition is quite small.

Vasquez & Purves (1979), Pflügers Arch. 379:157

autoregulation of cbf
Autoregulation of CBF
  • Between mean arterial pressures 60 – 160 torr, CBF ± constant (solid line).
    • at low pressures: dangerous drop in CBF; risk of syncope.
    • at high pressures: risk of oedema due to filtration↑ → intracranial P↑.
  • Myogenic response (partial)
  • In hypertension, right shift: risk of syncope↑ at start of therapy.
  • Intracranial P↑ → BP↑ (tumor; Cushing phenomenon) via ischaemicstimulation of vasomotor centre: homeostatic flow maintenance.

Patton et al. (1989), 21. ed.

local control of cbf
Local Control of CBF

Guyton & Hall (2006), 11. ed.

  • Regional neural activity↑ due to metabolism↑ causes local hyperaemia.
  • Exploited in fMRI (functional studies).
  • Primary mediators unknown: NO, adenosine, K+ (?).
  • Secondary mediators: ↑, ↓.
blood flow and
Blood Flow and
  • CBF very sensitive to changes in local :
    • vasodilation with ↑.
    • vasoconstriction with ↓
  • Very rapid response.
  • Mechanism: perivascular pH changes caused by CO2.
    • However, acidosis in vessel does not CBF↑ because of blood-brain barrier.
  • Affected by BP: CO2sensitivi-ty↓ with BP↓, and vice versa.
  • Hypercapnia abolishes auto-regulation (see resp. control).

Guyton & Hall (2006), 11. ed.

blood flow and1
Blood Flow and

Patton et al. (1989), 21. ed.

  • Little effect of on CBF under normal conditions; but with
    • mild hypoxia (45 torr): doubling of CBF; severe hypoxia (20 – 30 torr): maximal vasodilation (high altitude oedema…).
    • Hyperbaric hyperoxia: CBF↓ slightly (of little value…).
  • Metabolic or neural mechanism (?).
take home messages
Take-Home Messages
  • Coronary perfusion is largest during diastole.
  • Autoregulation renders flow independent of aortic pressure.
  • Metabolic effect more powerful than neuronal.
  • ATP, NO and adenosine play a crucial role in metabolically regulating cardiac perfusion.
  • Only large stenosis (>80%) causes a significant flow limitation at rest.
  • Cerebral vascular bed is special because it has a parasympathetic innervation.
  • Metabolism is the most important determinant of resistance.
  • Regulation happens at local level to limit volume changes.
  • is the most important determinant of CBF.
slide25
MCQ

Helmut Fringer, a 28 year-old medical student, has an assessment of his coronary circulation under strenuous exercise. Which of the following statements best describes the coronary circulation during exercise?

  • Increased O2 supply is mainly achieved via increased O2 extraction than an increase in blood flow.
  • Increased cardiac sympathetic fibre activity raises coronary perfusion.
  • Increased ATP availability contributes to vasodilation.
  • Blood flow is increased by release of acetylcholine.
  • Autoregulation is suppressed.
slide27
MCQ

Helmut Fringer, a 28 year-old medical student, has an assessment of his coronary circulation under strenuous exercise. Which of the following statements best describes the coronary circulation during exercise?

  • Increased O2 supply is mainly achieved via increased O2 extraction than an increase in blood flow.
  • Increased cardiac sympathetic fibre activity raises coronary perfusion.
  • Increased ATP availability contributes to vasodilation.
  • Blood flow is increased by release of acetylcholine.
  • Autoregulation is suppressed.