basics of cerebral blood supply and drainage and vasoactive drugs.

1. Cerebral blood
supply and effects
of vasoactive
drugs
Sunakshi bhatia
Pg resident anestheiology
Srg jhalawar

2. OBJECTIVES
• Arterial supply
• Venus drainage
• Blood brain barrier
• Vasoactive drus

3. CEREBRAL BLOOD SUPPLY
1.

4. 14%

5. 14 % of Cardiac output

6. 750ml/min
Blood flow

7. 3-3.8ml/100g/min
Oxygen requirement for brain

8. high oxygen consumption

9. no significant oxygen reserve

10. unconsciousness in 10 seconds

11. 3 minutes

12. continous supply of blood is
required

13. ARTERIAL SUPPLY

14. • Brain is supplied by two vertebral artery & two internal
carotid arteries
internal carotid arteries (70%)--- forebrain
vertebrobasilar system (30%)---posterior cortex, the
midbrain, and the brainstem
Interconnected by circle of wilis

15. Carotid artery
system

16. Common
carotid artery

17. Origin -right common carotid -from the brachiocephalic
trunk
- left common carotid - from arota
Split - external and internal carotid arteries
at upper border of the thyroid cartilage, at around the
level of the 4th cervical vertebra.

18. Arch of aorta
Sub-clavian arteries
Descending aorta
Common carotid ateries
Brachio-cephelic trunk
R common c
R sub clavian
L common c

20. Magnetic Resonance Angiography

21. Internal carotid
artery

22. • It reaches cranium after passing passing through carotid
canal & foramen lacerum.
• Inside the cranium it passes throug cavernous sinus
and then it lies next to optic chiasma

23. BRANCHES of internal carotid artery
splits into middle and anterior cerebral artery under the
anterior perforated substance

24. Before internal carotid artery splits into the
terminal branches, it gives off:

27. Terminal branches
• Middle cerebral
• Anterior cerebral

29. Particularly prominent are the lenticulostriate arteries that
branch from the middle cerebral artery.
These arteries supply the basal ganglia and thalamus.
*Clinical most
important
lacunar strokes represent about one-
fifth of all strokes
numbness.
Difficulty walking.
Difficulty speaking.
Clumsiness of a hand or arm.
Weakness or paralysis of eye muscles.

31. Functionally, the striatum coordinates multiple
aspects of cognition, including both motor and
action planning, decision-making, motivation,
reinforcement, and reward perception. The
striatum is made up of the caudate nucleus
and the lentiform nucleus.

32. Normal carotidal arteriography

34. posterior cerebral artery - occipital and inferior parts of the temporal
lobes.
Middle cerebral artery –lateral surface of brain
Anterior cerebral artery –medial surface of brain

35. Vertebro-basilar
System

36. Vertebral arteries
Basilar artery
Posterior cerebral
arteries

38. Join to form- basilar artery
at the level - pons on the ventral surface of the
brainstem
Branches -
1. spinal branches
2. meningeal branches
3. muscular branches
4. anterior spinal artery
5. posterior spinal artery
6. medullary branches
7. posterior inferior cerebellar artery

40. • meningeal branches - falx cerebelli and the posterior
cranial fossa
• anterior spinal arteries
posterior spinal artery
spinal branches -spinal cord.
• muscular branches - deep neck muscles
• posterior inferior cerebellar artery(PICA) -medulla
oblongata, the inferior vermis, the 4th ventricle choroid
plexus, the cerebellar hemisphere, and the dentate
nucleus.
• medullary branches -medulla oblongata.

41. Basilar artery

43. Clinical correlation
• narrowing of the vertebral or basilar arteries
caused by atherosclerosis creates
vertebrobasilar insufficiency

45. CIRCLE OF WILLIS

47. The circle of Willis consists of an arterial network located at
the skull base allowing arterial blood flow exchange between
the anterior and the posterior circulation, and between the
right and left hemispheres.
Site – at the base of the brain around the inter peduncular
fossa
also called – loop of Willis,cerebral arterial circle, and
Willis polygon
named after -Thomas Willis , an English physician.
Only 34%of people have the normal described anatomy

49. BRANCHES
1. Anterior cerebral artery (left and right)
2. Anterior communicating artery
3. Internal carotid artery (left and right)
4. Posterior cerebral artery (left and right)
5. Posterior communicating artery (left and right)
The middle cerebral arteries, supplying the brain, are not
considered part of the circle of Willis.

51. Function REDUNDANCY
The arrangement of the brain's arteries into the circle
of Willis creates redundancy (analogous to engineered
redundancy) for collateral circulation in the cerebral
circulation. If one part of the circle becomes blocked
or narrowed (stenosed) or one of the arteries
supplying the circle is blocked or narrowed, blood flow
from the other blood vessels can often preserve the
cerebral perfusion well enough to avoid the symptoms
of ischemia.

53. 1 Cortical branches – run on cortical
surface , anastamose with
adjacent cortical branches .
so when there is a block in these
it produces small infarct
2 Central branches – pass through
white matter , do not anastomose
so , if they are blocked it gives rise
to large infarct
Clinical correlation

54. Facts about circle of wilis.
1. it is incomplete in most individuals, although wide
variations exist.
1. Saccular aneurysms, the most common type of
aneurysm, originate in and around the circle of Willis at
the branching points of blood vessels.
1. Approximately 85–90% of aneurysms occur in the
anterior circulation

55. Clinical Correlation
• CONGENITAL CEREBRAL ANEURYSMS
These occur mostly at the sites where two arteries join in the formation
of the circle of Willis. The basic abnormality at these points is the
congenital deficiency of the tunica media (elastic tissue) in the arterial
wall. The aneurysms are berry-shaped, hence they are generally termed
berry aneurysms.
• SUBARACHNOID HAEMORRHAGE
The subarachnoid haemorrhage commonly but not exclusively results
from rupture of congenital berry aneurysms in the interpeduncular
cistern.
The subarachnoid haemorrhage produces a sudden severe pain in head
followed by mental confusion. The death may quickly occur, or the
patient may survive the first bleeding only to die few days or weeks later

57. c4

58. BLOODBRAIN BARRIER
2.

60. The interface between the walls of capillaries and the
surrounding tissue of brain is called the blood-brain barrier.
HISTORY
The special properties of the blood-brain barrier were first
observed by the nineteenth-century bacteriologist Paul
Ehrlich, who noted that intravenously injected dyes leaked
out of capillaries in most regions of the body to stain the
surrounding tissues; the brain, however, remained unstained .
He was wrong!
His student, Edwin Goldmann, showed that such dyes do not
traverse the specialized walls of brain capillaries.

61. • The restriction of large molecules like Ehrlich's dyes to the
vascular space is the result of tight junctions between
neighboring capillary endothelial cells in the brain.
• Such junctions are not found in capillaries elsewhere in
the body, where the spaces between adjacent endothelial
cells allow much more ionic and molecular traffic.

62. • Molecular entry into the brain should be determined by an
agent's solubility in lipids, the major constituent of cell
membranes.
• Nevertheless, many ions and molecules not readily
soluble in lipids do move quite readily from the vascular
space into brain tissue. A molecule like glucose, the
primary source of metabolic energy for neurons and glial
cells, is an obvious example.
• This paradox is explained by the presence of specific
transporters for glucose and other critical molecules and
ions.
• In addition to tight junctions, astrocytic “end feet” (the
terminal regions of astrocytic processes) surround the
outside of capillary endothelial cells.

63. • The blood-brain barrier is thus important for protection
and homeostasis. It also presents a significant problem for
the delivery of drugs to the brain.
• Large (or lipid-insoluble) molecules can be introduced to
the brain, but only by transiently disrupting the blood-
brain barrier with hyperosmotic agents like mannitol.
• Very high blood pressure can break this barrier.

64. VENOUS DRAINAGE
3.

65. VEINS OF BRAIN
INTRACRANIAL DURAL VENOUS
SINUSES
INTERNL JUGULAR VEINS OF NECK

66. Characterstic features of venous
drainage of brain :
1. Does not have arterial pattern
1. Extremely thin walled
3. No valves
4. Run in subarachnoid space

68. Superficial cerebral veins
Drain the cortex
3 groups:
1. Superior cerebral veins
2. Middle cerebral veins
3. Inferior cerebral veins.

69. Drain- Superolateral and Medial surface
superficial
a) Superfical m cerebral vein
b) Deep m cerebral vein
Inferior cerebral veins
Drains :
- Inferior surface,
- Lower parts of medial and superolateral
surfaces.

70. Superficial m. cerebral vein
Anteriorly, drains into cavernous
sinus.
- Posteriorly, communicates with
Superior saggital sinus through
superior anastomotic vein (of
Troland).
- With Transverse sinus via inferior
Anastomotic vein of Labbe.
deep m. cerebral vein
Joins anterior cerebral
vein to form the basal
vein.

72. other veins
Anterior cerebral vein:
- Accompanies anterior cerebral artery.
- Drains medial surface.
Basal vein terminate into Great cerebral vein of
Galen

73. • The cerebrum, cerebellum and brainstem are drained by
numerous veins, which empty into the dural venous
sinuses.
• The spinal cord is supplied by anterior and posterior spinal
veins, which drain into the internal and external vertebral
plexuses.

74. • location -periosteal and meningeal layers of the dura .
• They are best thought of as collecting pools of blood,
which drain the central nervous system, the face, and the
scalp.
• do not have valves.
• There are eleven venous sinuses in total.
Dural Venous Sinuses

75. 1. straight,2 .Superior,3. inferior sagittal sinuses are found in
the falx cerebri of the dura mater.
They converge at the confluence of sinuses (overlying the
internal occipital protuberance). The straight sinus is a
continuation of the great cerebral vein and the inferior
sagittal sinus.
From the confluence, the 4. transverse sinus continues bi-
laterally and curves into the 5.sigmoid sinus to meet the
opening of the internal jugular vein.
The 6.cavernous sinus drains the ophthalmic veins and can be
found on either side of the sella turcica. From here, the blood
returns to the internal jugular vein via the 7.superior or
inferior petrosal sinuses.

77. Veins of the Cerebrum
The veins of cerebrum are responsible for carrying blood from
the brain tissue, and depositing it in the dural venous sinuses.
arranged around the gyri and sulci of the brain.
Upon exiting the cerebral parenchyma, the veins run in the
subarachnoid space and pierce the meninges to drain into the
dural venous sinuses.
• Superficial System Drains- cerebral cortex
• Deep System Drains- Subependymal veins
The great cerebral vein (vein of Galen) is formed by the union
of two of the deep veins, and drains into the straight sinus.
Medullary veins: These drain the deep areas of the brain.

78. Other Structures in the Central Nervous
System

79. Cerebellum
The superior and inferior cerebellar veins. They empty into
the superior petrosal, transverse and straight dural venous
sinuses.
Brainstem
Examples of veins that drain the brainstem
1. transverse pontine vein
2. anteromedian medullary vein
3. anterior and posterior spinal veins.

80. Spinal Cord
• The spinal cord is supplied by three anterior and three
posterior spinal veins.
• These veins are valveless, and form an anastomotic
network along the surface of the spinal cord.
• They also receive venous blood from the radicular veins.
• spinal veins drain into internal and external vertebral
plexuses, which empty into systemic segmental veins.
• The internal vertebral plexus also empties into the dural
venous sinuses superiorly.

81. Drugs that affect heart and circulatory system
VASO-ACTIVE DRUGS
4.

82. BASIC PHYSIOLOGY

84. Sympathetic System
Preganglionic fibers originate from
• Thoracic (T1-T12) segments of the cord
• Lumbar (L1-L3) segments of the cord
Preganglionic fibers are short and the postganglionic fibers
are long
adrenergic originally referred to the effects of epinephrine
(adrenaline), although norepinephrine (noradrenaline) is the
primary neurotransmitter responsible for most of the adrenergic
activity of the sympathetic nervous system

88. All belong to superfamily of G-protein-coupled receptors

89. Broncho constriction
Uterine contraction
Inhibition of insulin
release and lipolysis
Smooth
muscles
vasoconstriction
Presynaptic
ones
Postsynaptic
ones
Sedation and sympathetic
outflow- vasodialation and
low bp
Chronotropic
Dropmoropic
ionotropic
Increse insuline
release

90. Adrenalin
e>noradr
enaline
Beta adrenoceptors: show strong
response to isoproterenol

91. Chronotropic- HR
Ionotropic- Contractility
Dromotropic-Conduction velocity
Bathmotropic- Excitability
Lusitropic- Relaxation

94. Ionotropic
*
D1

95. SYMPATHETIC NERVOUS SYSTEM
fight-or-flight response.
• accelerate the heart rate
• constrict blood vessels
• raise blood pressure.

96. Adrenergic
Agonist/symapthomi
metics

97. A)Catecholamines
Epinephrine, norepinephrine, isoproterenol, and dopamine
These compounds share the following properties:
1) High potency: show the highest potency in directly activating α or β receptors.
2) Rapid inactivation: rapidly metabolized by COMT and MAO, brief action.
3) Poor penetration into the CNS.
B)Non -Catecholamines prolonged duration of
action, because they are not inactivated by COMT and poor substrates
for MAO because MAO is an important route of detoxification. Increased
lipid solubility permits greater access to the CNS.

99. drug which reduces appetite

101. Dopamine
It is a relatively nonspecific agonist at both
dopamine1 (D1) and dopamine2 (D2) receptors and
the a- and b-adrenergic receptors. D1 receptors are
located postsynaptically. When activated D1 receptors
elicit vasodilation cerebral vascular beds
Endogenous NE release- 5 microgram/kg/min
B1 action-2-10 micogram/kg/min
B1 and a1 action- 10- 20 microgram/kg/min

102. Adrenaline
Epinephrine is poorly lipid soluble,
preventing its ready entrance
into the central nervous system (CNS) and
accounting for
the lack of cerebral effects.
B1 and b2- 2-10microgram/min
a1- >10 microgram/min
Cpr-1mg Iv

103. Nor- adrenaline
Vasopressor- 0.01-0.5 microgram/kg/min

104. Dobutamine
2.5-10 microgram/kg/min can be till 40
microgram/kg/min
*increases cardiac oxygen demand
Dobutamine is used to increase the cardiac output in
congestive heart failure, as well as for ionotropic
support after cardiac surgery.

105. Phenylephrine
raises both systolic and diastolic blood
pressure
Used to treat hypotension in hospitalized or
surgical patients
Infusion-100 microgram/min
Or bolus- 120-150 microgram iv

106. Adrenergic
Antagonist/sympatho
lytics

108. Adrenergic anetagonist

109. α ADRENERGIC BLOCKING DRUGS

112. Prazocin
Selective competitive blockers of the α1 receptor.
treatment of hypertension.
Cardiovascular effects: All of these agents decrease peripheral vascular
resistance and lower blood pressure by causing the relaxation of both
arterial and venous smooth muscle. Tamsulosin has the least effect on
blood pressure.
*
Tamsulosin and alfuzosin are indicated for the treatment of benign
prostatic hypertrophy (also known as benign prostatic hyperplasia or
BPH).

113. Phenoxybenzamine is
nonselective, linking
covalently to both α1 and α2 receptors
Actions:
Cardiovascular effects: By blocking α receptors,
phenoxybenzamine causes decreased peripheral
resistance.
Phenoxybenzamine is used in the treatment of
pheochromocytoma.

114. Phenylephrine
vasoconstriction
increases coronary perfusion pressure without chronotropic
side effects, unlike most other sympathomimetics so useful in
coronary artery disease and aortic stenosis
Phenylephrine has been used as a continuous infusion (20 to
100 g per minute) in adults to maintain normal blood
pressure during surgery.

115. β ADRENERGIC BLOCKING DRUGS

121. Labetolol
Dose-oral-100-400mg bd
5-20mg iv upto 300mg

122. Metoprolol
Oral- 100-400mg/day

123. Esmolol
rapid-onset and short-acting selective b1- adrenergic receptor
antagonist that is administered only IV
After a typical initial dose of 0.5 mg/kg IV over about 60
seconds, the full therapeutic effect is evident within 5
minutes, and its action ceases within 10 to 30 minutes after
administration is discontinued.
It useful drug for preventing or treating adverse systemic
blood pressure and heart rate increases that occur
intraoperative in response to noxious stimulation, as during
tracheal intubation.
Administered about 2 minutes before direct laryngoscopy

124. Classification of Vasoactive Drugs
1.Catecholamines
2.Phosphodiesterase inhibitors
3.Calcium Sensitizers
4.Vasopressors
5.Others

125. Catecholamines
1. Adrenaline (natural)
2. noradrenaline
3. dopamine
4. Dobutamine (synthetic)
5. isoprenaline(synthetic)
6. Dopexamine
Phosphodiesterase
inhibitors
1. milrinone
2. amrinone
3. Levosimendan
Vasopressors
1. Phenylephrine
2. ephedrine
3. vasopressin
4. Steroids
5. metaraminol
Vasodialators
1. sodium nitro prusside
2. nitroglycerine

127. Vasodialators
• Sodium nirtopruside
• Hydralazine
• NTG

129. Caution..
Vasodilators tend to:
1. Increase BP back to high levels by
a) Increasing Renin Release
b) Increasing Sympathetic outflow through the
baroreceptor reflex
2. Cause Reflex Tachycardia (Again increased reflex
sympathetic activity

130. • Most can cause palpitations and can precipitate angina
and arrhythmias due to the increased sympathetic activity
• They cause headache and flushing due to the
Vasodilatation
• They may also cause salt and water retention and thus
edema
• They do not cause postural Hypotension because
sympathetic reflexes are intact

131. Sod.nitropruside
Dose-0.5-2microgram/kg/min up to 10 microgram/kg/min
direct-acting, nonselective peripheral vasodilator that
causes relaxation of arte- rial and venous vascular smooth
muscle.
soluble in water
onset of action is almost immediate, equipotent on
arteries and veins, and its duration is transient, requiring
continuous IV administration to maintain a therapeutic
effect.
The extreme potency of SNP necessitates careful titration of
dosage as provided by continuous infusion devices and
frequent monitoring of systemic blood pressure.

132. • SNP increases cerebral blood flow and cerebral blood
volume.
• In patients with decreased intracranial compliance, this
may increase intracranial pressure
• the rapidity of systemic blood pressure decrease
produced by SNP exceeds the capacity of the cerebral
circulation to auto-regulate its blood flow such that
intracranial pressure and cerebral blood flow change
simultaneously but in opposite directions.
• Nevertheless, increases in intracranial pressure by SNP are
maximal during modest decreases (30%) in MAP.
• When SNP-induced decreases in mean arterial pressure are greater
than 30% , the intracranial pressure decreases to below the awake
level. Furthermore, decreasing blood pressure slowly over 5 minutes
with SNP in the presence of hypocarbia and hyperoxia negates the
increase in intracranial pressure that accompanies the rapid infusion
of nitroprusside.

133. *Patients with known inadequate cerebral blood flow as
associated with dangerously increased intracranial pressure or
carotid artery stenosis should probably not be treated with SNP
*Cyanide Poisoning: infusion rates of > 2
mg/kg/minute IV result in dose-dependent
accumulation of cyanide.
Due to uptake into RBCs with liberation of cyanide
*increase the area of damage associated with a
myocardial infarction through a phenomenon called
“coronary steal.”
The use of SNP, as mentioned earlier, has significantly declined with the
introduction of more selective arterial agents which have a greater
margin of safety and much less or absent toxicity.

134. NTG
Dose-5microgram/kg/min starting infusion
Then increment of 5 microgram/kg/min
Acts on-venous capacitance vessels and large coronary
arteries
most common use -angina pectoris
Controlled hypotension can also be achieved with the
continuous infusion of nitroglycerin.
nitrite metabolite of nitroglycerin is capable of oxidizing the
ferrous ion in hemoglobin to the ferric state with the
production of methemoglobin
*tolerence develops to vasodiation

135. FenoldopamNew dilator
dopamine type 1 receptor agonist
MOA
particular action of increasing renal blood flow and increasing
urine output and also increasing splanchnic blood flow due to
the density of dopamine type 1 receptors in these beds.
compared to other IV antihypertensive drugs such as SNP or
nicardipine, there is greater urine output with fenoldopam for
the same degree of antihypertensive action.
Adverse effects are limited to an increase in intraocular
pressure, making this drug unsuitable for patients with
glaucoma. *Causes natriuresis

136. Furoseminde
diuretics continue to be first-line oral agents used for
essential hypertension.
Patients are most likely to be prescribed a thiazide drug, with
more potent furosemide reserved for patients where
thiazides are less effective such as patients with renal
insufficiency or heart failure.
Diuretics are not, strictly speaking, vasodilators although
there evidence for a venodilating effect of IV furosemide

137. Vasoactive drugs
on brain

144. Effects of CBF & CPP on EEG
CBF & CPP SLOWING OF
EEG
FLATTENING OF
EEG
IRREVERSIBLE
BRAIN
DAMAGE
CBF
N-
50ml/100g/min
20-25 10-15 below 10
CPP=MAP-ICP
N=80-100mm
hg below 50 25-40 below 25

145. Vasopressors
• normal autoregulation and an intact blood–brain----
increase CBF only when mean arterial blood pressure is
below 50 mm Hg or above 150 mm Hg.
• absence of autoregulation- increase CBF by their effect on
CPP.
• β-Adrenergic agents seem to have a greater effect on the
brain when the blood–brain barrier is disrupted; central
β1-receptor stimulation increases CMR and blood flow.
• β-Adrenergic blockers generally have no direct effect on
CMR or CBF.
• Excessive elevations in blood pressure with any agent can
disrupt the blood–brain barrier.

146. Vasodilators
• absence of hypotension- cerebral vasodilation and
increase CBF in a dose-related fashion.
• When these agents decrease blood pressure, CBF is
usually maintained and may even increase.
• The resultant increase in cerebral blood volume can
elevate ICP in patients with decreased intracranial
compliance.

147. EFFECTS OF VASOACTIVE DRUGS ON CBF
• Alpha 1 agonist
Phenylephrine – increases CBF &
CPP transiently for 2-5 min after
bolus dose.
In a study it showed increase in
middle cerebral artery(MCA) flow
velocity & cerebral oxygen
saturation

148. • Ephedrine – increases arterial blood
pressure , blood flow & cerebral oxygen
saturation ( increases CO) espicailly when
bbb is open
• Nor epinephrine – usually no effect on
cerebral blood vessels . But
when BBB is defective then it
increases CBF by vasodialatation
• Epinephrine – increases CBF & more so
when BBB is injured

149. • Alpha 2 agonist
They have both analgesic & sedative effect on brain.
1. Clonidine – is less potent & specific
• treatment of hypertensive urgency Oral dosage (immediate-release
tablets)
• 0.1 to 0.2 mg PO every hour as required to a total of 0.6 mg.
2. Dexmeditomedine
approved for sedation rather than hypertension, although it does have a
blood pressure–lowering action.
infusion from 0.1 t o 1.5 mg/kg/minute
-- Reduces CMR & there by
it reduces CBF

150. • Beta agonist
- They increase CMR & there by CBF
- These effects are through beta 1
receptors
• Beta blockers
- Reduce cerebral blood flow
- Their effect depends on catecholamine
levels & BBB status

151. • Dopamine
Only levo form crossed bbb
In small doses dopamine increases cerebral
blood flow by vasodialatation
Very high dose cause vasoconstriction
• Dobutamine
It increases CMR & CBF

153. Effects of ephedrine, dobutamine and dopexamine on
cerebral haemodynamics: transcranial Doppler studies in
healthy Volunteers
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154. Thank you