Reperfusion injury
Encyclopedia
Reperfusion injury is the tissue
damage caused when blood
supply returns to the tissue after a period of ischemia
or lack of oxygen. The absence of oxygen
and nutrient
s from blood during the ischemic period creates a condition in which the restoration of circulation
results in inflammation
and oxidative damage through the induction of oxidative stress
rather than restoration of normal function.
s, carried to the area by the newly returning blood, release a host of inflammatory factors
such as interleukin
s as well as free radicals
in response to tissue damage. The restored blood flow reintroduces oxygen within cell
s that damages cellular protein
s, DNA
, and the plasma membrane. Damage to the cell's membrane may in turn cause the release of more free radicals. Such reactive species may also act indirectly in redox signaling
to turn on apoptosis
. Leukocytes may also bind to the endothelium
of small capillaries
, obstructing them and leading to more ischemia.
Reperfusion injury plays a part in the brain
's ischemic cascade
, which is involved in stroke
and brain trauma
. Similar failure processes are involved in brain failure following reversal of cardiac arrest
; control of these processes is the subject of ongoing research. Repeated bouts of ischemia and reperfusion injury also are thought to be a factor leading to the formation and failure to heal
of chronic wound
s such as pressure sores and diabetic foot
ulcers. Continuous pressure limits blood supply and causes ischemia, and the inflammation occurs during reperfusion. As this process is repeated, it eventually damages tissue enough to cause a wound
.
In prolonged ischemia (60 minutes or more), hypoxanthine
is formed as breakdown product of ATP
metabolism. The enzyme xanthine dehydrogenase
acts in reverse, that is as a xanthine oxidase
as a result of the higher availability of oxygen. This oxidation results in molecular oxygen being converted into highly reactive superoxide
and hydroxyl
radicals
. Xanthine oxidase also produces uric acid
, which may act as both a prooxidant and as a scavenger of reactive species such as peroxynitrite. Excessive nitric oxide
produced during reperfusion reacts with superoxide
to produce the potent reactive species peroxynitrite
. Such radicals and reactive oxygen species attack cell membrane lipids, proteins, and glycosaminoglycans, causing further damage. They may also initiate specific biological processes by redox signaling
.
Reperfusion can cause hyperkalemia
.
, demonstrated a strong potential benefit with further research ongoing.
, and it has been shown by a number of large, high-quality randomised trials to significantly improve survival and reduce brain damage after birth asphyxia in newborn infants, almost doubling the chance of normal survival. For a full review see Hypothermia therapy for neonatal encephalopathy
.
However, the therapeutic effect of hypothermia does not confine itself to metabolism and membrane stability. Another school of thought focuses on hypothermia’s ability to prevent the injuries that occur after circulation returns to the brain, or what is termed reperfusion injuries. In fact an individual suffering from an ischemic insult continues suffering injuries well after circulation is restored. In rats it has been shown that neurons often die a full 24 hours after blood flow returns. Some theorize that this delayed reaction derives from the various inflammatory immune responses that occur during reperfusion. These inflammatory responses cause intracranial pressure, pressure which leads to cell injury and in some situations cell death. Hypothermia has been shown to help moderate intracranial pressure and therefore to minimize the harmful effect of a patient’s inflammatory immune responses during reperfusion. Beyond this, reperfusion also increases free radical production. Hypothermia too has been shown to minimize a patient’s production of deadly free radicals during reperfusion. Many now suspect it is because hypothermia reduces both intracranial pressure and free radical production that hypothermia improves patient outcome following a blockage of blood flow to the brain.
(H2S) can have a protective effect against reperfusion injury.
Lactate has long been an indicator of poor prognosis after I/R injury. [10, 11] Lactate is formed under anaerobic conditions when pyruvate, instead of being covered into acetyl-CoA and entering the tricarboxylic acid cycle (TCA) cycle, is converted into lactate to generate NAD+ needed for glycolysis to continue. Aside from being a marker for the level of anaerobic metabolism occurring, lactate increases interleukin- 1β (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor–α (TNF-α). [12] Multi organ failure is well known to be caused by a dysfunctional systemic inflammatory process. [11, 13] Elevated plasma levels of proinflammatory cytokines TNF-α, IL-1β, and IL-6 indicate a poor prognosis in animal and patient studies of MOF. [11] TNFα and IL-1β mediate neutorphil infiltration into tissues and organs. [14-17] Activated neutrophils damage organs and tissue via release of protolytic enzymes, ROS, and vasoactive substances. [15, 18] These cytokines have been shown to cause lung damage in rats after I/R (hemorrhagic shock). [19]
Ketone bodies (e.g. D- betahydroxybuterate; DBHB) are produced in the liver by fatty acid β-oxidation and condensation of resulting acetyl-CoA. Ketones are known to be protective but the mechanism has not yet been elucidated. [20] Examples of their protective properties include:
Interestingly, when DBHB is the major energy source during hemorrhagic shock, excess lactate and H+ are inhibited. [27]
PPARs (PPARα, PPARβ, and PPARγ) are transcription factors that are activated by fatty acids (which are elevated in ground squirrels during the winter season). When activated, PPARs regulate the transcription of genes involved in lipid and carbohydrate metabolism, inflammation, and expression of mitochondrial uncoupling protein 1 (UCP-1). [28] The result of PPAR activation on metabolism is an increase fatty acid metabolism and a decrease glucose metabolism. In hibernating ground squirrels, PPARα depresses dehydrogenase pyruvate complex (PDC) via upregulation of puruvate dehydrogenase kinase 4 (PDK4), thus blocking entrance of glycolitic products into the TCA cycle. [29, 30]
Activation of PPARs also decreases inflammatory gene expression. Specifically, they suppress nuclear factor kappa-beta (NFΚB) activity and target genes of nuclear factor of activated T cells (NFAT), activator protein 1 (AP1), and signal transducers and activators of transcription (STATs). [29, 31] PPARs also block expression of inflammatory cytokines (IL-6) and have been shown to induce apoptosis of macrophages exposed to TNFα and interferon-γ. [31, 32]
Finally, activated PPARS induce the expression of mitochondrial uncoupling protein 1 (UCP-1). [29] Mitochondrial UCP-1 has the potential to reduce ROS produced via the electron transport chain (ETC) when there is a sudden burst in oxygen levels (as occurs during reperfusion). UCP-1 works by allowing hydrogen ions to reenter the mitochondrial matrix and be uncoupled from the ETC and oxygen consumption. This prevents a back up of ETC-intermediates and an increase in ROS generation.
PPARs have shown a protective role in I/R injury. Some examples include:
Overall hibernation-season ground squirrels show reduced injury to I/R injury. Protection from such injury may be influenced by a seasonal switch from carbohydrate to lipid metabolism resulting in a decrease in lactate formation, increase in ketone bodies, and activation of PPARs.
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
damage caused when blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
supply returns to the tissue after a period of ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
or lack of oxygen. The absence of oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
and nutrient
Nutrient
A nutrient is a chemical that an organism needs to live and grow or a substance used in an organism's metabolism which must be taken in from its environment. They are used to build and repair tissues, regulate body processes and are converted to and used as energy...
s from blood during the ischemic period creates a condition in which the restoration of circulation
Circulatory system
The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
results in inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and oxidative damage through the induction of oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
rather than restoration of normal function.
Mechanisms of reperfusion injury
The inflammatory response partially mediates the damage of reperfusion injury. White blood cellWhite blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s, carried to the area by the newly returning blood, release a host of inflammatory factors
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
such as interleukin
Interleukin
Interleukins are a group of cytokines that were first seen to be expressed by white blood cells . The term interleukin derives from "as a means of communication", and "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes"...
s as well as free radicals
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
in response to tissue damage. The restored blood flow reintroduces oxygen within cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s that damages cellular protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, and the plasma membrane. Damage to the cell's membrane may in turn cause the release of more free radicals. Such reactive species may also act indirectly in redox signaling
Redox signaling
Redox signaling is when free radicals, reactive oxygen species , and other electronically activated species such as nitric oxide act as biological messengers. Arguably, hydrogen sulfide and carbon monoxide are also redox signaling molecules...
to turn on apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. Leukocytes may also bind to the endothelium
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
of small capillaries
Capillary
Capillaries are the smallest of a body's blood vessels and are parts of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...
, obstructing them and leading to more ischemia.
Reperfusion injury plays a part in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
's ischemic cascade
Ischemic cascade
The ischemic cascade is a series of biochemical reactions that are initiated in the brain and other aerobic tissues after seconds to minutes of ischemia . This is typically secondary to stroke, injury, or cardiac arrest due to heart attack. Most ischemic neurons that die do so due to the...
, which is involved in stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
and brain trauma
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...
. Similar failure processes are involved in brain failure following reversal of cardiac arrest
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
; control of these processes is the subject of ongoing research. Repeated bouts of ischemia and reperfusion injury also are thought to be a factor leading to the formation and failure to heal
Wound healing
Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...
of chronic wound
Chronic wound
A chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time the way most wounds do; wounds that do not heal within three months are often considered chronic....
s such as pressure sores and diabetic foot
Diabetic foot
Diabetic foot ulcer is one of the major complications of diabetes mellitus, and probably the major component of the diabetic foot. It occurs in 15% of all patients with diabetes and precedes 84% of all lower leg amputations...
ulcers. Continuous pressure limits blood supply and causes ischemia, and the inflammation occurs during reperfusion. As this process is repeated, it eventually damages tissue enough to cause a wound
Wound
A wound is a type of injury in which skin is torn, cut or punctured , or where blunt force trauma causes a contusion . In pathology, it specifically refers to a sharp injury which damages the dermis of the skin.-Open:...
.
In prolonged ischemia (60 minutes or more), hypoxanthine
Hypoxanthine
Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids where it is present in the anticodon of tRNA in the form of its nucleoside inosine. It has a tautomer known as 6-Hydroxypurine. Hypoxanthine is a necessary additive in certain cell,...
is formed as breakdown product of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
metabolism. The enzyme xanthine dehydrogenase
Xanthine dehydrogenase
Xanthine dehydrogenase, also known as XDH, is a protein that, in humans, is encoded by the XDH gene.-Function:Xanthine dehydrogenase belongs to the group of molybdenum-containing hydroxylases involved in the oxidative metabolism of purines. The enzyme is a homodimer...
acts in reverse, that is as a xanthine oxidase
Xanthine oxidase
Xanthine oxidase Xanthine oxidase Xanthine oxidase (XO (sometimes 'XAO'), a form of xanthine oxidoreductase that generates reactive oxygen species. Is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid...
as a result of the higher availability of oxygen. This oxidation results in molecular oxygen being converted into highly reactive superoxide
Superoxide
A superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...
and hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
radicals
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
. Xanthine oxidase also produces uric acid
Uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
, which may act as both a prooxidant and as a scavenger of reactive species such as peroxynitrite. Excessive nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
produced during reperfusion reacts with superoxide
Superoxide
A superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...
to produce the potent reactive species peroxynitrite
Peroxynitrite
Peroxynitrite is the anion with the formula ONOO−. It is an unstable structural isomer of nitrate, NO3−, which has the same formula but a different structure. Although peroxynitrous acid is highly reactive, its conjugate base peroxynitrite is stable in basic solution...
. Such radicals and reactive oxygen species attack cell membrane lipids, proteins, and glycosaminoglycans, causing further damage. They may also initiate specific biological processes by redox signaling
Redox signaling
Redox signaling is when free radicals, reactive oxygen species , and other electronically activated species such as nitric oxide act as biological messengers. Arguably, hydrogen sulfide and carbon monoxide are also redox signaling molecules...
.
Reperfusion can cause hyperkalemia
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
.
Treatment
A study of aortic cross-clamping, a common procedure in cardiac surgeryCardiac surgery
Cardiovascular surgery is surgery on the heart or great vessels performed by cardiac surgeons. Frequently, it is done to treat complications of ischemic heart disease , correct congenital heart disease, or treat valvular heart disease from various causes including endocarditis, rheumatic heart...
, demonstrated a strong potential benefit with further research ongoing.
Therapeutic hypothermia
An intriguing area of research demonstrates the ability of a reduction in body temperature to limit ischemic injuries. This procedure is called therapeutic hypothermiaTherapeutic hypothermia
Therapeutic hypothermia, also known as protective hypothermia, is a medical treatment that lowers a patient's body temperature in order to help reduce the risk of the ischemic injury to tissue following a period of insufficient blood flow. Periods of insufficient blood flow may be due to cardiac...
, and it has been shown by a number of large, high-quality randomised trials to significantly improve survival and reduce brain damage after birth asphyxia in newborn infants, almost doubling the chance of normal survival. For a full review see Hypothermia therapy for neonatal encephalopathy
Hypothermia therapy for neonatal encephalopathy
Brain hypothermia, induced by cooling a baby to around 33°C for three days after birth, is a treatment for birth asphyxia. It has recently been proven to be the only medical intervention which reduces brain damage, and improves an infant's chance of normal survival...
.
However, the therapeutic effect of hypothermia does not confine itself to metabolism and membrane stability. Another school of thought focuses on hypothermia’s ability to prevent the injuries that occur after circulation returns to the brain, or what is termed reperfusion injuries. In fact an individual suffering from an ischemic insult continues suffering injuries well after circulation is restored. In rats it has been shown that neurons often die a full 24 hours after blood flow returns. Some theorize that this delayed reaction derives from the various inflammatory immune responses that occur during reperfusion. These inflammatory responses cause intracranial pressure, pressure which leads to cell injury and in some situations cell death. Hypothermia has been shown to help moderate intracranial pressure and therefore to minimize the harmful effect of a patient’s inflammatory immune responses during reperfusion. Beyond this, reperfusion also increases free radical production. Hypothermia too has been shown to minimize a patient’s production of deadly free radicals during reperfusion. Many now suspect it is because hypothermia reduces both intracranial pressure and free radical production that hypothermia improves patient outcome following a blockage of blood flow to the brain.
Hydrogen sulfide treatment
There are some preliminary studies that seem to indicate that treatment with hydrogen sulfideHydrogen sulfide
Hydrogen sulfide is the chemical compound with the formula . It is a colorless, very poisonous, flammable gas with the characteristic foul odor of expired eggs perceptible at concentrations as low as 0.00047 parts per million...
(H2S) can have a protective effect against reperfusion injury.
Ischemia/Reperfusion Protection in Obligatory Hibernators, Ground Squirrels
Obligatory hibernators such as the ground squirrels have been show to have resistance to ischemia/reperfusion (I/R) injury in liver, heart, and small intestine during the hibernation season when there is a switch from carbohydrate metabolism to lipid metabolism for cellular energy supply. [1-9] This metabolic switch limits anaerobic metabolism and the formation of lactate, a herald of poor prognosis and multi organ failure (MOF) after I/R injury. [10, 11] In addition, the increase in circulating lipids and lipid metabolism generates ketone bodies and activates peroxisomal proliferating-activated receptors (PPARs), both of which have been shown to be protective against I/R injury.Lactate has long been an indicator of poor prognosis after I/R injury. [10, 11] Lactate is formed under anaerobic conditions when pyruvate, instead of being covered into acetyl-CoA and entering the tricarboxylic acid cycle (TCA) cycle, is converted into lactate to generate NAD+ needed for glycolysis to continue. Aside from being a marker for the level of anaerobic metabolism occurring, lactate increases interleukin- 1β (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor–α (TNF-α). [12] Multi organ failure is well known to be caused by a dysfunctional systemic inflammatory process. [11, 13] Elevated plasma levels of proinflammatory cytokines TNF-α, IL-1β, and IL-6 indicate a poor prognosis in animal and patient studies of MOF. [11] TNFα and IL-1β mediate neutorphil infiltration into tissues and organs. [14-17] Activated neutrophils damage organs and tissue via release of protolytic enzymes, ROS, and vasoactive substances. [15, 18] These cytokines have been shown to cause lung damage in rats after I/R (hemorrhagic shock). [19]
Ketone bodies (e.g. D- betahydroxybuterate; DBHB) are produced in the liver by fatty acid β-oxidation and condensation of resulting acetyl-CoA. Ketones are known to be protective but the mechanism has not yet been elucidated. [20] Examples of their protective properties include:
- Decreases in brain injury to neurons subject to ischemia. [21, 22]
- Reduced oxidative stress in cardiac tissue. [23, 24]
- Reduced oxidative stress in neurons by increasing NADH oxidation in the mitochondria and inhibiting reactive oxygen species (ROS) production. [25]
- Increased survival time in rats after hemorrhagic shock when resuscitated with a DBHB and melatonin (an antioxidant) infusion solution. [26]
Interestingly, when DBHB is the major energy source during hemorrhagic shock, excess lactate and H+ are inhibited. [27]
PPARs (PPARα, PPARβ, and PPARγ) are transcription factors that are activated by fatty acids (which are elevated in ground squirrels during the winter season). When activated, PPARs regulate the transcription of genes involved in lipid and carbohydrate metabolism, inflammation, and expression of mitochondrial uncoupling protein 1 (UCP-1). [28] The result of PPAR activation on metabolism is an increase fatty acid metabolism and a decrease glucose metabolism. In hibernating ground squirrels, PPARα depresses dehydrogenase pyruvate complex (PDC) via upregulation of puruvate dehydrogenase kinase 4 (PDK4), thus blocking entrance of glycolitic products into the TCA cycle. [29, 30]
Activation of PPARs also decreases inflammatory gene expression. Specifically, they suppress nuclear factor kappa-beta (NFΚB) activity and target genes of nuclear factor of activated T cells (NFAT), activator protein 1 (AP1), and signal transducers and activators of transcription (STATs). [29, 31] PPARs also block expression of inflammatory cytokines (IL-6) and have been shown to induce apoptosis of macrophages exposed to TNFα and interferon-γ. [31, 32]
Finally, activated PPARS induce the expression of mitochondrial uncoupling protein 1 (UCP-1). [29] Mitochondrial UCP-1 has the potential to reduce ROS produced via the electron transport chain (ETC) when there is a sudden burst in oxygen levels (as occurs during reperfusion). UCP-1 works by allowing hydrogen ions to reenter the mitochondrial matrix and be uncoupled from the ETC and oxygen consumption. This prevents a back up of ETC-intermediates and an increase in ROS generation.
PPARs have shown a protective role in I/R injury. Some examples include:
- PPARγ activation reduced liver apoptosis in rats after hemorrhagic shock. [33]
- PPARγ activation reduces systemic inflammation and lung injury after hemorrhagic shock. [34, 35]
- PPARγ expression is altered in ground squirrel intestine during the hibernation season and may contribute to the I/R-resistant phenotype. [36]
- During cardiac I/R, hibernating ground squirrels have reduced damage to myocardial tissue. In correlation with this, they also showed elevated PPARα-induced myocardial fatty acid utilization, reduced NFΚB activity and, reduced levels of circulating inflammatory cytokines (TNFα and IL-6). [9]
Overall hibernation-season ground squirrels show reduced injury to I/R injury. Protection from such injury may be influenced by a seasonal switch from carbohydrate to lipid metabolism resulting in a decrease in lactate formation, increase in ketone bodies, and activation of PPARs.
See also
- Crush syndromeCrush syndromeCrush syndrome is a medical condition characterized by major shock and renal failure after a crushing injury to skeletal muscle...
- IschemiaIschemiaIn medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
- Myocardial infarction — Reperfusion
- Therapeutic hypothermiaTherapeutic hypothermiaTherapeutic hypothermia, also known as protective hypothermia, is a medical treatment that lowers a patient's body temperature in order to help reduce the risk of the ischemic injury to tissue following a period of insufficient blood flow. Periods of insufficient blood flow may be due to cardiac...
- Hypothermia therapy for neonatal encephalopathyHypothermia therapy for neonatal encephalopathyBrain hypothermia, induced by cooling a baby to around 33°C for three days after birth, is a treatment for birth asphyxia. It has recently been proven to be the only medical intervention which reduces brain damage, and improves an infant's chance of normal survival...