Ischemia Flashcards
Roots
Isch - restriction Hema - blood
Definition of Ischemia
Definition: a decrease in effective blood flow that is incompatible with continuing organ function
Brain ischemia
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
Normal blood flow (BF)
Human 55 ml/100g/min (Grey) Rat 150 ml/100g/min
Factors affecting BF
Systemic BP, autoregulation, mean arterial BP: 45-160 mmHg Intracranial pressure Effective perfusion pressure: difference between arterial and intracranial pressure
Limit
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.
Type of brain ischemia
Complete vs incomplete Reversible vs irreversible Focal vs global Hemorrhage vs nonhemorrhagic
Examples:
Hypotension Stroke Cardiac arrest Decapitation
Focal vs global ischemia
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.
Focal ischemia
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
Ischemic stroke
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
Hemorrhagic stroke
Hemorrhagic stroke 20%, bleeding Intracerebral hemorrhage (ICH) Blood is released into the brain parenchyma Subarachnoid hemorrhage (SAH) Blood is released into the subarachnoid space
Major arterial supply of brain
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
Treatment for stroke: Ischemic stroke
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.
Treatment for stroke: Hemorrhagic stroke
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
Global ischemia
Irreversible Reversible: cardiac arrest/CPR, hypotension, increase in intracranial pressure
Cardiac arrest and resuscitation:
background and significance 6 month survival rate: <10%
Cardiac arrest vs heart attack
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.
How does cardiac arrest caused neurologic deficits?
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
Therapeutic hypothermia
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.
Focal ischemia stroke models
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
Endpoints
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
Animal models of global ischemia
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*
Global ischemia
Irreversible Reversible: cardiac arrest/CPR, hypotension, increase in intracranial pressure
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
Brain blood flow following cardiac arrest and resuscitation in rat
ADO 1h restored to levels similar to non-arrested vs untreated 1h
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
Animal Models
CA causes damage by
Arterial Supply to Brain
Ischemic Stroke
PCAS
Animal Models 2
FCI models
PCAS 2
Virchow
Ischemia
ischemia models
Reperfusion Brain Injury
Hemmorhagic Stroke
Factors affecting CBF
Endpoints
Ischemia Diagram
Fig 1
Autoregulation
Study
Ischemic Cascade Interference
Focal vs Global
CARS events
Images
Ischemic Cascade Full
CA events
Focal Ischemia
BP and Temp
HVR
Study
Global Ischemia Animal Models
Images
HVR
Scheme 1
MCAO Model
MCAO Graph
Hypoxia and Survival
CC after CAR
Delayed Selective Neuronal Death
Infarction
Photoreceptors
BBF after CAR
pH
