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Pathophysiology - ischemia - reperfusion injury
Ischemia-reperfusion injury is a phenomenon that cellular function and metabolic disorders and structural damage will worsen after organs or tissues restore blood supply. Its main mechanisms include increased free radical generation, calcium overload, and the role of microvascular and leukocytes. The heart and brain are common damaged organs, manifested as changes in myocardial metabolism and ultrastructural changes, decreased cardiac function, etc. Prevention and control measures include removing free radicals, reducing calcium overload, improving metabolism and controlling reperfusion conditions, such as low sodium, low temperature, low pressure, etc. Understanding these mechanisms can help develop effective treatment options and alleviate ischemic injury.
Edited at 2025-03-10 15:39:46- Rumi 10 spiritual high-dimensional awakenings
Rumi: 10 dimensions of spiritual awakening. When you stop looking for yourself, you will find the entire universe because what you are looking for is also looking for you. Anything you do persevere every day can open a door to the depths of your spirit. In silence, I slipped into the secret realm, and I enjoyed everything to observe the magic around me, and didn't make any noise. Why do you like to crawl when you are born with wings? The soul has its own ears and can hear things that the mind cannot understand. Seek inward for the answer to everything, everything in the universe is in you. Lovers do not end up meeting somewhere, and there is no parting in this world. A wound is where light enters your heart.
- Pathophysiology - Heart failure
Chronic heart failure is not just a problem of the speed of heart rate! It is caused by the decrease in myocardial contraction and diastolic function, which leads to insufficient cardiac output, which in turn causes congestion in the pulmonary circulation and congestion in the systemic circulation. From causes, inducement to compensation mechanisms, the pathophysiological processes of heart failure are complex and diverse. By controlling edema, reducing the heart's front and afterload, improving cardiac comfort function, and preventing and treating basic causes, we can effectively respond to this challenge. Only by understanding the mechanisms and clinical manifestations of heart failure and mastering prevention and treatment strategies can we better protect heart health.
- Pathophysiology - ischemia - reperfusion injury
Ischemia-reperfusion injury is a phenomenon that cellular function and metabolic disorders and structural damage will worsen after organs or tissues restore blood supply. Its main mechanisms include increased free radical generation, calcium overload, and the role of microvascular and leukocytes. The heart and brain are common damaged organs, manifested as changes in myocardial metabolism and ultrastructural changes, decreased cardiac function, etc. Prevention and control measures include removing free radicals, reducing calcium overload, improving metabolism and controlling reperfusion conditions, such as low sodium, low temperature, low pressure, etc. Understanding these mechanisms can help develop effective treatment options and alleviate ischemic injury.
Pathophysiology - ischemia - reperfusion injury
- Rumi 10 spiritual high-dimensional awakenings
Rumi: 10 dimensions of spiritual awakening. When you stop looking for yourself, you will find the entire universe because what you are looking for is also looking for you. Anything you do persevere every day can open a door to the depths of your spirit. In silence, I slipped into the secret realm, and I enjoyed everything to observe the magic around me, and didn't make any noise. Why do you like to crawl when you are born with wings? The soul has its own ears and can hear things that the mind cannot understand. Seek inward for the answer to everything, everything in the universe is in you. Lovers do not end up meeting somewhere, and there is no parting in this world. A wound is where light enters your heart.
- Pathophysiology - Heart failure
Chronic heart failure is not just a problem of the speed of heart rate! It is caused by the decrease in myocardial contraction and diastolic function, which leads to insufficient cardiac output, which in turn causes congestion in the pulmonary circulation and congestion in the systemic circulation. From causes, inducement to compensation mechanisms, the pathophysiological processes of heart failure are complex and diverse. By controlling edema, reducing the heart's front and afterload, improving cardiac comfort function, and preventing and treating basic causes, we can effectively respond to this challenge. Only by understanding the mechanisms and clinical manifestations of heart failure and mastering prevention and treatment strategies can we better protect heart health.
- Pathophysiology - ischemia - reperfusion injury
Ischemia-reperfusion injury is a phenomenon that cellular function and metabolic disorders and structural damage will worsen after organs or tissues restore blood supply. Its main mechanisms include increased free radical generation, calcium overload, and the role of microvascular and leukocytes. The heart and brain are common damaged organs, manifested as changes in myocardial metabolism and ultrastructural changes, decreased cardiac function, etc. Prevention and control measures include removing free radicals, reducing calcium overload, improving metabolism and controlling reperfusion conditions, such as low sodium, low temperature, low pressure, etc. Understanding these mechanisms can help develop effective treatment options and alleviate ischemic injury.
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- Outline
Section 1: Causes and influencing factors of ischemia-reperfusion injury
concept
After the ischemic organ or tissue regains blood supply, the metabolic disorders of cell function and structural damage will worsen
This phenomenon of further aggravation of ischemic injury after blood reperfusion is called ischemia-reperfusion injury
reason
Recover blood supply after ischemia of tissues and organs
Shock microcirculation clearance
Relieving coronary A spasm
Cardiac and cerebropulmonary resuscitation after cardiac arrest, etc.
Certain surgical procedures
Arterial bypass surgery, thrombolysis therapy, cardiac surgery extracorporeal circulation, organ transplantation, etc.
Factors
Ischemia time
The ischemia time is short, and there will be no obvious reperfusion injury after restoring blood supply. Because all organs can tolerate ischemia for a certain period of time
If the ischemia is long, restoring blood supply can easily lead to reperfusion injury. If the ischemia is too long, irreversible damage or even necrosis will occur in the ischemic organ, and there will be no reperfusion injury.
Side branch circulation
If the collateral circulation after ischemia is easily formed, reperfusion injury may be less likely to occur due to shortening the time of ischemia and reducing the degree of ischemia.
Aerobic Demand
Oxygen is easy to accept electrons, and forms more oxygen radicals. → Those with high oxygen demand will be more likely to undergo reperfusion damage.
e.g. Heart, brain, etc.
Reperfusion conditions
Perfusion of low pressure, low temperature (25℃), low pH, low sodium and low calcium solutions can reduce tissue and organ reperfusion damage and quickly restore its function.
High pressure, high temperature, high pH, high sodium and high calcium perfusion can induce or aggravate reperfusion injury.
Section 2 Mechanism of ischemia-reperfusion injury
The role of free radicals
Free radical species
Oxygen radicals
O2•-
Together with H2O2, it is collectively referred to as reactive oxygen species
OH•
Lipid free radicals
other
NO, CH3, etc.
The mechanism of increasing oxygen radical generation
Xanthine oxidation
Material basis
Xanthine oxidase (XO) increase
Cause: Ischemia and hypoxia → Cell membrane destroys Ca2 inflow ↑ → Calcium overload, activates many enzymes → One of the enzymes catalyzes
Xanthine dehydrogenase XD→XO
XO substrate increase
Substrate
Hypoxanthine
Xanthine
Hypoxia → ATP gradually decomposes and increases, and eventually produces hypopurine/xanthine
Conditional Basics
There is O2 when blood supply is restored →
XO oxidizes hypoxanthine to produce xanthine, and at the same time generates oxygen free radicals
Xanthine continues to react under XO, and also releases oxygen free radicals
Neutrophils – Respiratory burst
Ischemia and hypoxia increase metabolites (complement, leukotriene, etc.) → Chemotactics → Local neutrophils → When blood supply is restored, the centriole cells consume a large amount of O2 → its purpose is to produce oxygen free radicals to kill certain harmful substances → but it produces too much, which will damage the body
Impaired mitochondrial function
Damage to the cytochrome oxidase system
Under normal circumstances, O2 accepts 4e-generates H2O
abnormal
1e-
O2•-
2e-
H2O2
Not oxygen radical, but also strong oxidation
3e-
OH•
Ca2 overload in mitochondria
Catecholamine autooxidation
Ischemia → Stress → Catecholamine ↑ → Its oxidation effect produces a large number of free radicals
The damage effect of free radicals
Lipid peroxidation
Destroy membrane structure
Ion flow disorder on both sides of the membrane
Causing calcium overload, etc.
Mitochondrial membrane is destroyed
Reduce ATP synthesis
Indirect inhibition of membrane protein function
Ion pump
Vector
Promote the generation of free radicals and other biologically active substances
e.g. membrane phospholipids destroy to form arachidonic acid
Thrombin
Prostaglandin, etc.
Protein function inhibition
Mainly oxidizes -SH to form -S-S-
Probable protein polymers
Destroy nucleic acids and chromosomes
OH • Hydroxylated Bases
Causes gene mutations, etc.
Even causing DNA breakage
......
Calcium overload
Intracellular calcium overload mechanism
Na /Ca2 exchange exception
High Na intracellular
Ischemia and hypoxia cause Na inflow → When oxygen is regained, Na is transferred outward → Ca2 is exchanged inwardly.
High H intracellular
First, H-Na exchange occurs (acidosis causes both H in and out of the cell, but when oxygen is regained, extracellular H is ↓ but the intracellularity is still high) → high sodium in the cell→ activate Na-Ca2 exchange
Protein kinase C
Biofilm damage
Cell membrane
Sarcoplasmic net
After being destroyed, the Ca2 is released into the cytoplasm → Intracellular calcium overload
Mechanism of ischemia-reperfusion injury
Mitochondrial dysfunction
Damage to the cytochrome oxidase system
Structural damage
GTP generation↓
Activate multiple phospholipases
Wide range of damage
Ischemia-reperfusion arrhythmia
Mainly ventricular arrhythmia
Ventricular tachycardia
Vary fibrillation, etc.
Promote oxygen radical formation
Calcium overload →XO↑
Myofibrils hypercontraction
Even broken
Microvascular damage and leukocyte effects
Vascular endothelial and leukocyte activation during reperfusion
Some adhesion molecules involved
e. CD11 and CD18 on the surface of leukocytes
Intercellular adhesion molecule-1 on the surface of endothelial cells, endothelial cells-leukocyte adhesion molecule-1, etc.
Adhesion between leukocytes and endothelial cells (which have a repulsion effect under normal circumstances) → white blood cells adhere to the wall, roll, etc. → hinder blood flow
Vascular endothelial and neutrophil-mediated ischemia-reperfusion injury
Microvascular injury
No reflow phenomenon
After the coronary artery of the dog causes local myocardial ischemia, the ligated artery will be opened to reopen the blood flow, and the ischemic area cannot be fully perfused.
Major injuries
Microvascular hemoritic changes
Mainly the interaction between leukocytes (larger size) and endothelial cells
Microvascular diameter reduction
Locally produced blood vessel shrinking substances
Vascular endothelial cells swell and even rupture
Increased permeability of microvascular
The role of oxygen radicals, leukotrienes and other substances
Cell damage
Section 3 Changes in body function and metabolism
Cardiac ischemia-reperfusion injury
main
Changes in cardiac function
Reperfusion arrhythmia
Myocardial comfort function↓
Myocardial metabolic changes
ATP↓
Myocardial ultrastructural changes
Cerebral ischemia-reperfusion injury
Second
Changes in cell metabolism
ATP↓
Histological morphological changes
Other organs
Section 4 The basics of disease prevention and treatment
Reduce ischemic injury and control reperfusion conditions
Side branch circulation
Low sodium, low temperature, low pressure, low pH
Improves the metabolism of ischemic tissue
Scavenge free radicals
Low molecular scavenger
VE, VA, etc.
Enzyme scavenger
Catalyst CAT
Superoxide dismutase SOD
Scavenge superoxide anions
Reduce calcium overload
Control ischemia and hypoxia
Use energy mixture to make the cell pump run normally
Ischemia-Reperfusion Injury
Section 1: Causes and influencing factors of ischemia-reperfusion injury
concept
After the ischemic organ or tissue regains blood supply, the metabolic disorders of cell function and structural damage will worsen
This phenomenon of further aggravation of ischemic injury after blood reperfusion is called ischemia-reperfusion injury
reason
Recover blood supply after ischemia of tissues and organs
Shock microcirculation clearance
Relieving coronary A spasm
Cardiac and cerebropulmonary resuscitation after cardiac arrest, etc.
Certain surgical procedures
Arterial bypass surgery, thrombolysis therapy, cardiac surgery extracorporeal circulation, organ transplantation, etc.
Factors
Ischemia time
The ischemia time is short, and there will be no obvious reperfusion injury after restoring blood supply. Because all organs can tolerate ischemia for a certain period of time
If the ischemia is long, restoring blood supply can easily lead to reperfusion injury. If the ischemia is too long, irreversible damage or even necrosis will occur in the ischemic organ, and there will be no reperfusion injury.
Side branch circulation
If the collateral circulation after ischemia is easily formed, reperfusion injury may be less likely to occur due to shortening the time of ischemia and reducing the degree of ischemia.
Aerobic Demand
Oxygen is easy to accept electrons, and forms more oxygen radicals. → Those with high oxygen demand will be more likely to undergo reperfusion damage.
e.g. Heart, brain, etc.
Reperfusion conditions
Perfusion of low pressure, low temperature (25℃), low pH, low sodium and low calcium solutions can reduce tissue and organ reperfusion damage and quickly restore its function.
High pressure, high temperature, high pH, high sodium and high calcium perfusion can induce or aggravate reperfusion injury.
Section 2 Mechanism of ischemia-reperfusion injury
The role of free radicals
Free radical species
Oxygen radicals
O2•-
Together with H2O2, it is collectively referred to as reactive oxygen species
OH•
Lipid free radicals
other
NO, CH3, etc.
The mechanism of increasing oxygen radical generation
Xanthine oxidation
Material basis
Xanthine oxidase (XO) increase
Cause: Ischemia and hypoxia → Cell membrane destroys Ca2 inflow ↑ → Calcium overload, activates many enzymes → One of the enzymes catalyzes
Xanthine dehydrogenase XD→XO
XO substrate increase
Substrate
Hypoxanthine
Xanthine
Hypoxia → ATP gradually decomposes and increases, and eventually produces hypopurine/xanthine
Conditional Basics
There is O2 when blood supply is restored →
XO oxidizes hypoxanthine to produce xanthine, and at the same time generates oxygen free radicals
Xanthine continues to react under XO, and also releases oxygen free radicals
Neutrophils – Respiratory burst
Ischemia and hypoxia increase metabolites (complement, leukotriene, etc.) → Chemotactics → Local neutrophils → When blood supply is restored, the centriole cells consume a large amount of O2 → its purpose is to produce oxygen free radicals to kill certain harmful substances → but it produces too much, which will damage the body
Impaired mitochondrial function
Damage to the cytochrome oxidase system
Under normal circumstances, O2 accepts 4e-generates H2O
abnormal
1e-
O2•-
2e-
H2O2
Not oxygen radical, but also strong oxidation
3e-
OH•
Ca2 overload in mitochondria
Catecholamine autooxidation
Ischemia → Stress → Catecholamine ↑ → Its oxidation effect produces a large number of free radicals
The damage effect of free radicals
Lipid peroxidation
Destroy membrane structure
Ion flow disorder on both sides of the membrane
Causing calcium overload, etc.
Mitochondrial membrane is destroyed
Reduce ATP synthesis
Indirect inhibition of membrane protein function
Ion pump
Vector
Promote the generation of free radicals and other biologically active substances
e.g. membrane phospholipids destroy to form arachidonic acid
Thrombin
Prostaglandin, etc.
Protein function inhibition
Mainly oxidizes -SH to form -S-S-
Probable protein polymers
Destroy nucleic acids and chromosomes
OH • Hydroxylated Bases
Causes gene mutations, etc.
Even causing DNA breakage
......
Calcium overload
Intracellular calcium overload mechanism
Na /Ca2 exchange exception
High Na intracellular
Ischemia and hypoxia cause Na inflow → When oxygen is regained, Na is transferred outward → Ca2 is exchanged inwardly.
High H intracellular
First, H-Na exchange occurs (acidosis causes both H in and out of the cell, but when oxygen is regained, extracellular H is ↓ but the intracellularity is still high) → high sodium in the cell→ activate Na-Ca2 exchange
Protein kinase C
Biofilm damage
Cell membrane
Sarcoplasmic net
After being destroyed, the Ca2 is released into the cytoplasm → Intracellular calcium overload
Mechanism of ischemia-reperfusion injury
Mitochondrial dysfunction
Damage to the cytochrome oxidase system
Structural damage
GTP generation↓
Activate multiple phospholipases
Wide range of damage
Ischemia-reperfusion arrhythmia
Mainly ventricular arrhythmia
Ventricular tachycardia
Vary fibrillation, etc.
Promote oxygen radical formation
Calcium overload →XO↑
Myofibrils hypercontraction
Even broken
Microvascular damage and leukocyte effects
Vascular endothelial and leukocyte activation during reperfusion
Some adhesion molecules involved
e. CD11 and CD18 on the surface of leukocytes
Intercellular adhesion molecule-1 on the surface of endothelial cells, endothelial cells-leukocyte adhesion molecule-1, etc.
Adhesion between leukocytes and endothelial cells (which have a repulsion effect under normal circumstances) → white blood cells adhere to the wall, roll, etc. → hinder blood flow
Vascular endothelial and neutrophil-mediated ischemia-reperfusion injury
Microvascular injury
No reflow phenomenon
After the coronary artery of the dog causes local myocardial ischemia, the ligated artery will be opened to reopen the blood flow, and the ischemic area cannot be fully perfused.
Major injuries
Microvascular hemoritic changes
Mainly the interaction between leukocytes (larger size) and endothelial cells
Microvascular diameter reduction
Locally produced blood vessel shrinking substances
Vascular endothelial cells swell and even rupture
Increased permeability of microvascular
The role of oxygen radicals, leukotrienes and other substances
Cell damage
Section 3 Changes in body function and metabolism
Cardiac ischemia-reperfusion injury
main
Changes in cardiac function
Reperfusion arrhythmia
Myocardial comfort function↓
Myocardial metabolic changes
ATP↓
Myocardial ultrastructural changes
Cerebral ischemia-reperfusion injury
Second
Changes in cell metabolism
ATP↓
Histological morphological changes
Other organs
Section 4 The basics of disease prevention and treatment
Reduce ischemic injury and control reperfusion conditions
Side branch circulation
Low sodium, low temperature, low pressure, low pH
Improves the metabolism of ischemic tissue
Scavenge free radicals
Low molecular scavenger
VE, VA, etc.
Enzyme scavenger
Catalyst CAT
Superoxide dismutase SOD
Scavenge superoxide anions
Reduce calcium overload
Control ischemia and hypoxia
Use energy mixture to make the cell pump run normally