Ischemia Flashcards

1
Q

Roots

A

Isch - restriction Hema - blood

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2
Q

Definition of Ischemia

A

Definition: a decrease in effective blood flow that is incompatible with continuing organ function

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3
Q

Brain ischemia

A

2% of the total body weight in humans; it receives 15-20% of the body’s blood supply The brain uses 20% of available oxygen for normal function, making tight regulation of blood flow and oxygen delivery critical for survival

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4
Q

Normal blood flow (BF)

A

Human 55 ml/100g/min (Grey) Rat 150 ml/100g/min

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5
Q

Factors affecting BF

A

Systemic BP, autoregulation, mean arterial BP: 45-160 mmHg Intracranial pressure Effective perfusion pressure: difference between arterial and intracranial pressure

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6
Q

Limit

A

Above and below this limit, autoregulation is lost and CBF becomes dependent on MAP in a linear fashion. When CPP falls below the lower limit of autoregulation, cerebral ischemia ensures.

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7
Q

Type of brain ischemia

A

Complete vs incomplete Reversible vs irreversible Focal vs global Hemorrhage vs nonhemorrhagic

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8
Q

Examples:

A

Hypotension Stroke Cardiac arrest Decapitation

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9
Q

Focal vs global ischemia

A

Global ischemia occurs when cerebral blood flow is reduced throughout most or all of the brain Focal ischemia is represented by a reduction in blood flow to a very distinct, specific brain region.

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10
Q

Focal ischemia

A

Stroke 3rd most common cause of death The most common cause of adult disability In US >700,000 strokes occur annually leading to 200,000 deaths 4 million stroke survivors, half of them with some degree of disabilit

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11
Q

Ischemic stroke

A

80%, blockage of a brain artery, e.g., middle cerebral artery (MCA) Cerebral thrombosis: a thrombus (clot) that develops at the clogged part of the vessel Cerebral embolism: a blood clot that forms at another location in the circulatory system Virchow (1821-1902): known for elucidating the mechanism of pulmonary thromboembolism, coining the terms embolism and thrombosis

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12
Q

Hemorrhagic stroke

A

Hemorrhagic stroke 20%, bleeding Intracerebral hemorrhage (ICH) Blood is released into the brain parenchyma Subarachnoid hemorrhage (SAH) Blood is released into the subarachnoid space

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13
Q

Major arterial supply of brain

A

Internal carotid artery - middle cerebral artery Vertebral artery - basilar artery The circle of Willis (aka cerebral arterial circle and Willis Polygon) is a circulatory anastomosis that supplies blood to the brain and surrounding structures. Named after Thomas Willis (1621-1675), an English physician. Components: Anterior cerebral artery Anterior communicating artery Internal carotid artery Posterior cerebral artery Posterior communicating artery

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14
Q

Treatment for stroke: Ischemic stroke

A

tPA, the gold standard The only FDA approved treatment is tissue plasminogen activator (tPA). tPA works by dissolving the clot and improving blood flow. If administered within three hours (and up to 4.5 hours) tPA may improve the chances of recovering from a stroke. Endovascular procedures To remove the large blood clot. The procedure should be done within six hours of acute stroke symptoms, and only after a patient receives tPA.

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15
Q

Treatment for stroke: Hemorrhagic stroke

A

Endovascular procedures Less invasive, involving the use of a catheter introduced through a major artery in the leg or arm, then guided to the aneurysm; it then deposits a mechanical agent, such as a coil, to prevent rupture Surgical treatment

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16
Q

Global ischemia

A

Irreversible Reversible: cardiac arrest/CPR, hypotension, increase in intracranial pressure

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17
Q

Cardiac arrest and resuscitation:

A

background and significance 6 month survival rate: <10%

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18
Q

Cardiac arrest vs heart attack

A

A cardiac arrest is when the heart stops beating, or goes into a rhythm that cannot circulate blood effectively. Patients usually lose a pulse, become unresponsive, and stop breathing. A heart attack specifically refers to a process where there is an obstruction in one of the coronary arteries (which supplies oxygen to the heart itself), often as a result of atherosclerosis. A heart attack can cause a cardiac arrest- sometime at the same time, or sometimes years later.

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19
Q

How does cardiac arrest caused neurologic deficits?

A

Ischemia/reperfusion injury Ischemia Anoxia Increase excitability (excessive calcium and glutamate excretion) Mitochondrial and cellular death Cerebral edema BBB impairment Reperfusion injury Inflammatory response Free radical formation Continued cell damage, worsening the inflammatory response, which exacerbates cerebral edema

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20
Q

Therapeutic hypothermia

A

Therapeutic hypothermia (aka targeted temperature management) refers to deliberate reduction of the core body temperature, typically to a range of about 32° to 3°C (89.6° to 93.2°F) in patients who don’t regain consciousness after return of spontaneous circulation following a cardiac arrest. Hypothermia Counteracts neuroexcitation in brain cells by stabilizing calcium and glutamate release, reducing the degree of cell death Stabilizes the BBB and suppresses the inflammatory process, reducing cerebral edema Cerebral metabolism decreases 6 to 10% for every degree C that body temperature drops. As cerebral metabolism declines, the brain needs less oxygen.

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21
Q

Focal ischemia stroke models

A

MIddle cerebral artery occlusion (MCAO) First developed in 1980s Craniectomy Intraluminal suture MCAO (rats and mice) Reversible (temporal) Mimic: spontaneous thrombus dissolution (rare), or tissue plasminogen activator (tPA) is used to dissolve clot and restore circulation Permanent

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22
Q

Endpoints

A

Behavioral performance in motor or neurological disorder Infarct volume determination Infarction: a localized area of ischemic necrosis resulting from an interruption of either its arterial supply or venous drainage

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23
Q

Animal models of global ischemia

A

Two-vessel occlusion model of forebrain ischemia Transient bilateral common carotid artery (CCA) occlusion plus hypotension (50 mmHg) Four-vessel occlusion model of forebrain ischemia Transient bilateral common carotid artery (CCA) occlusion plus permanent vertebral artery occlusions Cardiac arrest and resuscitation* Endpoints Selective neuronal death Neurological recovery Survival*

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24
Q

Global ischemia

A

Irreversible Reversible: cardiac arrest/CPR, hypotension, increase in intracranial pressure

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25
Delayed selective neuronal death:
hippocampal CA1 region Image: hippocampal CA1 neurons four days after cardiac arrest and resuscitation in rat Non-arrested and ADO-treated similar vs untreated
26
Brain blood flow following cardiac arrest and resuscitation in rat
ADO 1h restored to levels similar to non-arrested vs untreated 1h
27
Differentiate the following conditions due to impairment of cerebral circulation
Gray out and whiteout: Loss of color vision Hypoxia Low blood pressure Positive G force Shock, loss of blood Blackout: Complete loss of vision Redout: Blood is driven to the head and causes reddening of the visual field and headache - retinal damage and hemorrhagic stroke Negative G force
28
Animal Models
29
CA causes damage by
30
Arterial Supply to Brain
31
Ischemic Stroke
32
PCAS
33
Animal Models 2
34
FCI models
35
PCAS 2
36
Virchow
37
Ischemia
38
ischemia models
39
Reperfusion Brain Injury
40
Hemmorhagic Stroke
41
Factors affecting CBF
42
Endpoints
43
Ischemia Diagram
44
Fig 1
45
Autoregulation
46
Study
47
Ischemic Cascade Interference
48
Focal vs Global
49
CARS events
50
Images
51
Ischemic Cascade Full
52
CA events
53
Focal Ischemia
54
BP and Temp
55
HVR
56
Study
57
Global Ischemia Animal Models
58
Images
59
HVR
60
Scheme 1
61
MCAO Model
62
MCAO Graph
63
Hypoxia and Survival
64
CC after CAR
65
Delayed Selective Neuronal Death
66
Infarction
67
Photoreceptors
68
BBF after CAR
69
pH