Reperfusion injury

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Reperfusion injury
Other namesReperfusion insult
Ischemic preconditioning of the heart.png
Native records of contractile activity of the left ventricle of isolated rat heart perfused under Langendorff technique. Curve A - contractile function of the heart is greatly depressed after ischemia-reperfusion. Curve B - a set of short ischemic episodes (ischemic preconditioning) before prolonged ischemia provides functional recovery of contractile activity of the heart at reperfusion.
Specialty Cardiology   OOjs UI icon edit-ltr-progressive.svg

Reperfusion injury, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue ( re- + perfusion ) after a period of ischemia or lack of oxygen (anoxia or hypoxia). The absence of oxygen and nutrients 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 (or along with) restoration of normal function.

Contents

Reperfusion injury is distinct from cerebral hyperperfusion syndrome (sometimes called "Reperfusion syndrome"), a state of abnormal cerebral vasodilation.

Mechanisms

Reperfusion of ischemic tissues is often associated with microvascular injury, particularly due to increased permeability of capillaries and arterioles that lead to an increase of diffusion and fluid filtration across the tissues. Activated endothelial cells produce more reactive oxygen species but less nitric oxide following reperfusion, and the imbalance results in a subsequent inflammatory response. [1] The inflammatory response is partially responsible for the damage of reperfusion injury. White blood cells, carried to the area by the newly returning blood, release a host of inflammatory factors such as interleukins as well as free radicals in response to tissue damage. [2] The restored blood flow reintroduces oxygen within cells that damages cellular proteins, 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. White blood cells may also bind to the endothelium of small capillaries, obstructing them and leading to more ischemia. [2]

Reperfusion injury plays a major part in the biochemistry of hypoxic brain injury in stroke. Similar failure processes are involved in brain failure following reversal of cardiac arrest; [3] 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 wounds such as pressure sores and diabetic foot ulcer. [4] 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. [4]

The main reason for the acute phase of ischemia-reperfusion injury is oxygen deprivation and, therefore, arrest of generation of ATP (cellular energy currency) by mitochondria oxidative phosphorylation. Tissue damage due to the general energy deficit during ischemia is followed by reperfusion (increase of oxygen level) when the injury is enhanced. Mitochondrial complex I is thought to be the most vulnerable enzyme to tissue ischemia/reperfusion but the mechanism of damage is different in different tissues. For example brain ischemia/reperfusion injury is mediated via complex I redox-dependent inactivation. [5] It was found that lack of oxygen leads to conditions in which mitochondrial complex I loses its natural cofactor, flavin mononucleotide (FMN) and become inactive. [6] When oxygen is present the enzyme catalyzes a physiological reaction of NADH oxidation by ubiquinone, supplying electrons downstream of the respiratory chain (complexes III and IV). Ischemia leads to dramatic increase of succinate level. [7] In the presence of succinate mitochondria catalyze reverse electron transfer so that fraction of electrons from succinate is directed upstream to FMN of complex I. [8] Reverse electron transfer results in a reduction of complex I FMN, increased generation of ROS, followed by a loss of the reduced cofactor (FMNH2) and impairment of mitochondria energy production. [8] The FMN loss by complex I and I/R injury can be alleviated by the administration of FMN precursor, riboflavin. [6]

Reperfusion can cause hyperkalemia. [9]

Reperfusion injury is a primary concern in liver transplantation surgery. [10]

Treatment

Therapeutic hypothermia

However,[ clarification needed ] 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. [11] 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. [12]

Hydrogen sulfide treatment

There are some preliminary studies in mice that seem to indicate that treatment with hydrogen sulfide (H2S) can have a protective effect against reperfusion injury. [13]

Cyclosporin

In addition to its well-known immunosuppressive capabilities, the one-time administration of cyclosporin at the time of percutaneous coronary intervention (PCI) has been found to deliver a 40 percent reduction in infarct size in a small group proof of concept study of human patients with reperfusion injury published in The New England Journal of Medicine in 2008. [14]

Cyclosporin has been confirmed in studies to inhibit the actions of cyclophilin D, a protein which is induced by excessive intracellular calcium flow to interact with other pore components and help open the MPT pore. Inhibiting cyclophilin D has been shown to prevent the opening of the MPT pore and protect the mitochondria and cellular energy production from excessive calcium inflows. [15]

However, the studies CIRCUS and CYCLE (published in September 2015 and February 2016 respectively) looked at the use of cyclosporin as a one time IV dose given right before perfusion therapy (PCI). Both studies found there is no statistical difference in outcome with cyclosporin administration. [16] [17]

Reperfusion leads to biochemical imbalances within the cell that lead to cell death and increased infarct size. More specifically, calcium overload and excessive production of reactive oxygen species in the first few minutes after reperfusion set off a cascade of biochemical changes that result in the opening of the so-called mitochondrial permeability transition pore (MPT pore) in the mitochondrial membrane of cardiac cells. [15]

The opening of the MPT pore leads to the inrush of water into the mitochondria, resulting in mitochondrial dysfunction and collapse. Upon collapse, the calcium is then released to overwhelm the next mitochondria in a cascading series of events that cause mitochondrial energy production supporting the cell to be reduced or stopped completely. The cessation of energy production results in cellular death. Protecting mitochondria is a viable cardioprotective strategy. [18]

In 2008, an editorial in the New England Journal of Medicine called for more studies to determine if cyclosporin can become a treatment to ameliorate reperfusion injury by protecting mitochondria. [18] To that end, in 2011 the researchers involved in the original 2008 NEJM study initiated a phase III clinical study of reperfusion injury in 1000 myocardial infarction patients in centers throughout Europe. Results of that study were announced in 2015 and indicated that "intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year." [16] This same process of mitochondrial destruction through the opening of the MPT pore is implicated in making traumatic brain injuries much worse. [19]

TRO40303

TRO40303 is a new cardioprotective compound that was shown to inhibit the MPT pore and reduce infarct size after ischemia-reperfusion. It was developed by Trophos company and currently is in Phase I clinical trial. [20]

Stem cell therapy

Recent investigations suggest a possible beneficial effect of mesenchymal stem cells on heart and kidney reperfusion injury. [21] [22]

Superoxide dismutase

Superoxide dismutase is an effective anti-oxidant enzyme which converts superoxide anions to water and hydrogen peroxide. Recent researches have shown significant therapeutic effects on pre-clinical models of reperfusion injury after ischemic stroke. [23] [24]

Metformin

A series of 2009 studies published in the Journal of Cardiovascular Pharmacology suggest that Metformin may prevent cardiac reperfusion injury by inhibition of Mitochondrial Complex I and the opening of MPT pore and in rats. [25] [26]

Riboflavin

In neonatal in vivo model of brain ischemia/reperfusion, tissue injury can be alleviated by the administration of FMN precursor, riboflavin that prevents inactivation of mitochondrial complex I. [6] [27]

Cannabinoids

A study published in 2012 show that the synthetic analogue of the phytocannabinoid Tetrahydrocannabivarin (THCV), Δ8-Tetrahydrocannabivarin (Δ8-THCV) and its metabolite 11-OH-Δ8-THCV, prevent hepatic ischaemia/reperfusion injury by decreasing oxidative stress and inflammatory responses through cannabinoid CB2 receptors and thereby decrease tissue injury and inflammation with a protective effect against liver damage. Pretreatment with a CB2 receptor antagonist attenuated the protective effects of Δ8-THCV, while a CB1 antagonist tended to enhance it. [28]

An earlier study published in 2011 found, that Cannabidiol (CBD) also protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response of oxidative and nitrative stress, and thereby cell death and tissue injury, but independent from classical CB1 and CB2 receptors. [29]

Reperfusion protection in obligate hibernators

Obligatory hibernators such as the ground squirrels show 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. [30] [31] [32] 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. In addition, the increase in lipid metabolism generates ketone bodies and activates peroxisome proliferating-activated receptors (PPARs), both of which have been shown to be protective against I/R injury. [33]

See also

Related Research Articles

<span class="mw-page-title-main">Respiratory complex I</span> Protein complex involved in cellular respiration

Respiratory complex I, EC 7.1.1.2 is the first large protein complex of the respiratory chains of many organisms from bacteria to humans. It catalyzes the transfer of electrons from NADH to coenzyme Q10 (CoQ10) and translocates protons across the inner mitochondrial membrane in eukaryotes or the plasma membrane of bacteria.

<span class="mw-page-title-main">Ciclosporin</span> Chemical compound

Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephrotic syndrome, eczema, and in organ transplants to prevent rejection. It is also used as eye drops for keratoconjunctivitis sicca.

<span class="mw-page-title-main">Ischemia</span> Restriction in blood supply to tissues

Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism. Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue i.e. hypoxia and microvascular dysfunction. It also implies local hypoxia in a part of a body resulting from constriction.

<span class="mw-page-title-main">Flavin mononucleotide</span> Chemical compound

Flavin mononucleotide (FMN), or riboflavin-5′-phosphate, is a biomolecule produced from riboflavin (vitamin B2) by the enzyme riboflavin kinase and functions as the prosthetic group of various oxidoreductases, including NADH dehydrogenase, as well as cofactor in biological blue-light photo receptors. During the catalytic cycle, a reversible interconversion of the oxidized (FMN), semiquinone (FMNH•), and reduced (FMNH2) forms occurs in the various oxidoreductases. FMN is a stronger oxidizing agent than NAD and is particularly useful because it can take part in both one- and two-electron transfers. In its role as blue-light photo receptor, (oxidized) FMN stands out from the 'conventional' photo receptors as the signaling state and not an E/Z isomerization.

<span class="mw-page-title-main">Lipid emulsion</span>

Lipid emulsion or fat emulsion refers to an emulsion of fat for human intravenous use, to administer nutrients to critically-ill patients that cannot consume food. It is often referred to by the brand name of the most commonly used version, Intralipid, which is an emulsion containing soybean oil, egg phospholipids and glycerin, and is available in 10%, 20% and 30% concentrations. The 30% concentration is not approved for direct intravenous infusion, but should be mixed with amino acids and dextrose as part of a total nutrient admixture.

The mitochondrial permeability transition pore is a protein that is formed in the inner membrane of the mitochondria under certain pathological conditions such as traumatic brain injury and stroke. Opening allows increase in the permeability of the mitochondrial membranes to molecules of less than 1500 daltons in molecular weight. Induction of the permeability transition pore, mitochondrial membrane permeability transition, can lead to mitochondrial swelling and cell death through apoptosis or necrosis depending on the particular biological setting.

Ischemic preconditioning (IPC) is an experimental technique for producing resistance to the loss of blood supply, and thus oxygen, to tissues of many types. In the heart, IPC is an intrinsic process whereby repeated short episodes of ischaemia protect the myocardium against a subsequent ischaemic insult. It was first identified in 1986 by Murry et al. This group exposed anesthetised open-chest dogs to four periods of 5 minute coronary artery occlusions followed by a 5-minute period of reperfusion before the onset of a 40-minute sustained occlusion of the coronary artery. The control animals had no such period of “ischaemic preconditioning” and had much larger infarct sizes compared with the dogs that did. The exact molecular pathways behind this phenomenon have yet to be fully understood.

<span class="mw-page-title-main">SOD2</span> Enzyme

Superoxide dismutase 2, mitochondrial (SOD2), also known as manganese-dependent superoxide dismutase (MnSOD), is an enzyme which in humans is encoded by the SOD2 gene on chromosome 6. A related pseudogene has been identified on chromosome 1. Alternative splicing of this gene results in multiple transcript variants. This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the superoxide byproducts of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), premature aging, sporadic motor neuron disease, and cancer.

<span class="mw-page-title-main">Brain mitochondrial carrier protein 1</span> Protein-coding gene in the species Homo sapiens

Brain mitochondrial carrier protein 1 is a protein that in humans is encoded by the SLC25A14 gene.

No reflow phenomenon is the failure of blood to reperfuse an ischemic area after the physical obstruction has been removed or bypassed. The underlying mechanism is related to arterial microvasculature damage. It is primarily seen during percutaneous coronary intervention (PCI) in the setting of acute myocardial infarction (AMI), but has also been observed in other organs, including the brain and kidneys. Coronary no-reflow phenomenon is specifically related to reduced antegrade coronary blood flow despite proximal coronary artery patency. It is an independent predictor of worse clinical outcomes including heart failure, fatal arrhythmias, myocardial infarction, and increased mortality rates.

<span class="mw-page-title-main">VDAC3</span> Protein-coding gene in the species Homo sapiens

Voltage-dependent anion-selective channel protein 3 (VDAC3) is a protein that in humans is encoded by the VDAC3 gene on chromosome 8. The protein encoded by this gene is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms. Nonetheless, VDAC3 demonstrates limited pore-forming ability and, instead, interacts with other proteins to perform its biological functions, including sperm flagella assembly and centriole assembly. Mutations in VDAC3 have been linked to male infertility, as well as Parkinson’s disease.

Reverse electron flow (also known as reverse electron transport) is a mechanism in microbial metabolism. Chemolithotrophs using an electron donor with a higher redox potential than NAD(P)+/NAD(P)H, such as nitrite or sulfur compounds, must use energy to reduce NAD(P)+. This energy is supplied by consuming proton motive force to drive electrons in a reverse direction through an electron transport chain and is thus the reverse process as forward electron transport. In some cases, the energy consumed in reverse electron transport is five times greater than energy gained from the forward process. Autotrophs can use this process to supply reducing power for inorganic carbon fixation.

Survivor Activating Factor Enhancement (SAFE) is a metabolic pathway. It is an intrinsic protective signaling program to limit cell death activated by the heart. This pathway allows ischaemic postconditioning that helps protect against reperfusion injury. This path involves the activation of a transcription factor called signal transducer and activator of transcription 3 (STAT3). The SAFE pathway interacts with the reperfusion injury salvage kinase pathway to convey the ischemic postconditioning stimulus from the cell surface to the mitochondria, where many of the prosurvival and death signals appear to converge.

<span class="mw-page-title-main">Rottlerin</span> Chemical compound

Rottlerin (mallotoxin) is a polyphenol natural product isolated from the Asian tree Mallotus philippensis. Rottlerin displays a complex spectrum of pharmacology.

<span class="mw-page-title-main">Necroptosis</span> Programmed form of necrosis, or inflammatory cell death

Necroptosis is a programmed form of necrosis, or inflammatory cell death. Conventionally, necrosis is associated with unprogrammed cell death resulting from cellular damage or infiltration by pathogens, in contrast to orderly, programmed cell death via apoptosis. The discovery of necroptosis showed that cells can execute necrosis in a programmed fashion and that apoptosis is not always the preferred form of cell death. Furthermore, the immunogenic nature of necroptosis favors its participation in certain circumstances, such as aiding in defence against pathogens by the immune system. Necroptosis is well defined as a viral defense mechanism, allowing the cell to undergo "cellular suicide" in a caspase-independent fashion in the presence of viral caspase inhibitors to restrict virus replication. In addition to being a response to disease, necroptosis has also been characterized as a component of inflammatory diseases such as Crohn's disease, pancreatitis, and myocardial infarction.

Diallyl trisulfide (DATS), also known as Allitridin, is an organosulfur compound with the formula S(SCH2CH=CH2)2. It is one of several compounds produced by hydrolysis of allicin, including diallyl disulfide and diallyl tetrasulfide; DATS is one of the most potent.

Cardioprotection includes all mechanisms and means that contribute to the preservation of the heart by reducing or even preventing myocardial damage. Cardioprotection encompasses several regimens that have shown to preserve function and viability of cardiac muscle cell tissue subjected to ischemic insult or reoxygenation. Cardioprotection includes strategies that are implemented before an ischemic event, during an ischemic event and after the event and during reperfusion. These strategies can be further stratified by performing the intervention locally or remotely, creating classes of conditioning known as remote ischemic PC (RIPC), remote ischemic PostC and remote ischemic PerC. Classical (local) preconditioning has an early phase with an immediate onset lasting 2–3 hours that protects against myocardial infarction. The early phase involves post-translational modification of preexisting proteins, brought about by the activation of G protein-coupled receptors as well as downstream MAPK's and PI3/Akt. These signaling events act on the ROS-generating mitochondria, activate PKCε and the Reperfusion Injury Salvage Kinase (RISK) pathway, preventing mitochondrial permeability transition pore (MTP) opening. The late phase with an onset of 12–24 hours that lasts 3–4 days and protects against both infarction and reversible postischemic contractile dysfunction, termed myocardial stunning. This phase involves the synthesis of new cardioprotective proteins stimulated by nitric oxide (NO), ROS and adenosine acting on kinases such as PKCε and Src, which in turn activate gene transcription and upregulation of late PC molecular players.

Ischemia-reperfusion (IR) tissue injury is the resultant pathology from a combination of factors, including tissue hypoxia, followed by tissue damage associated with re-oxygenation. IR injury contributes to disease and mortality in a variety of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Whether resulting from traumatic vessel disruption, tourniquet application, or shock, the extremity is exposed to an enormous flux in vascular perfusion during a critical period of tissue repair and regeneration. The contribution of this ischemia and subsequent reperfusion on post-traumatic musculoskeletal tissues is unknown; however, it is likely that similar to cardiac and kidney tissue, IR significantly contributes to tissue fibrosis.

Kidney ischemia is a disease with a high morbidity and mortality rate. Blood vessels shrink and undergo apoptosis which results in poor blood flow in the kidneys. More complications happen when failure of the kidney functions result in toxicity in various parts of the body which may cause septic shock, hypovolemia, and a need for surgery. What causes kidney ischemia is not entirely known, but several pathophysiology relating to this disease have been elucidated. Possible causes of kidney ischemia include the activation of IL-17C and hypoxia due to surgery or transplant. Several signs and symptoms include injury to the microvascular endothelium, apoptosis of kidney cells due to overstress in the endoplasmic reticulum, dysfunctions of the mitochondria, autophagy, inflammation of the kidneys, and maladaptive repair.

Roberta Anne Gottlieb is an American oncologist, academic, and researcher. She is a Professor, and Vice-Chair of Translational Medicine in the Department of Biomedical Sciences at Cedars-Sinai Medical Center, and a Professor of Medicine at the University of California, Los Angeles.

References

  1. ↑ Carden, Donna L.; Granger, D. Neil (February 2000). "Pathophysiology of ischaemia-reperfusion injury". The Journal of Pathology. 190 (3): 255–266. doi: 10.1002/(SICI)1096-9896(200002)190:3<255::AID-PATH526>3.0.CO;2-6 . PMID   10685060. S2CID   37383438.
  2. 1 2 Reperfusion Injury in Stroke at eMedicine
  3. ↑ Hendry, Robert; Crippen, David (2007). "Brain failure and brain death". In Fink, Mitchell P.; Jurkovic, Gregory J. (eds.). ACS Surgery: Principles and Practice. B C Decker. pp. 1609–1612. ISBN   978-1-55009-399-5.
  4. 1 2 Mustoe, Thomas (May 2004). "Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy". The American Journal of Surgery. 187 (5): S65–S70. doi:10.1016/S0002-9610(03)00306-4. PMID   15147994.
  5. ↑ Galkin, A (November 2019). "Brain Ischemia/Reperfusion Injury and Mitochondrial Complex I Damage". Biochemistry. Biokhimiia. 84 (11): 1411–1423. doi:10.1134/S0006297919110154. PMID   31760927. S2CID   207990089.
  6. 1 2 3 Stepanova, Anna; Sosunov, Sergey; Niatsetskaya, Zoya; Konrad, Csaba; Starkov, Anatoly A.; Manfredi, Giovanni; Wittig, Ilka; Ten, Vadim; Galkin, Alexander (20 September 2019). "Redox-Dependent Loss of Flavin by Mitochondrial Complex I in Brain Ischemia/Reperfusion Injury". Antioxidants & Redox Signaling. 31 (9): 608–622. doi:10.1089/ars.2018.7693. PMC   6657304 . PMID   31037949.
  7. ↑ Sahni, Prateek V; Zhang, Jimmy; Sosunov, Sergey; Galkin, Alexander; Niatsetskaya, Zoya; Starkov, Anatoly; Brookes, Paul S; Ten, Vadim S (February 2018). "Krebs cycle metabolites and preferential succinate oxidation following neonatal hypoxic-ischemic brain injury in mice". Pediatric Research. 83 (2): 491–497. doi:10.1038/pr.2017.277. PMC   5866163 . PMID   29211056.
  8. 1 2 Stepanova, Anna; Kahl, Anja; Konrad, Csaba; Ten, Vadim; Starkov, Anatoly S; Galkin, Alexander (December 2017). "Reverse electron transfer results in a loss of flavin from mitochondrial complex I: Potential mechanism for brain ischemia reperfusion injury". Journal of Cerebral Blood Flow & Metabolism. 37 (12): 3649–3658. doi:10.1177/0271678X17730242. PMC   5718331 . PMID   28914132.
  9. ↑ Atlee, John L. (2007). Complications in Anesthesia. Elsevier Health Sciences. pp. 55–. ISBN   978-1-4160-2215-2.
  10. ↑ Lemasters and, John J.; Thurman, Ronald G. (April 1997). "Reperfusion injury after liver preservation for transplantation". Annual Review of Pharmacology and Toxicology. 37 (1): 327–338. doi:10.1146/annurev.pharmtox.37.1.327. PMID   9131256.
  11. ↑ "Back to Life: The Science of Reviving the Dead". Newsweek. 22 July 2007.
  12. ↑ Polderman, Kees H. (1 April 2004). "Application of therapeutic hypothermia in the ICU: opportunities and pitfalls of a promising treatment modality. Part 1: Indications and evidence". Intensive Care Medicine. 30 (4): 556–575. doi:10.1007/s00134-003-2152-x. PMID   14767591. S2CID   5733761.
  13. ↑ Elrod, John W; Calvert, John W; Duranski, Mark R; Lefer, David J (31 October 2006). "Abstract 947: Hydrogen Sulfide Donor Protects Against Acute Myocardial Ischemia-Reperfusion Injury". Circulation. 114 (suppl_18): II_172. doi:10.1161/circ.114.suppl_18.II_172-a (inactive 31 January 2024).{{cite journal}}: CS1 maint: DOI inactive as of January 2024 (link)
  14. ↑ Piot, Christophe; Croisille, Pierre; Staat, Patrick; Thibault, Hélène; Rioufol, Gilles; Mewton, Nathan; Elbelghiti, Rachid; Cung, Thien Tri; Bonnefoy, Eric; Angoulvant, Denis; Macia, Christophe; Raczka, Franck; Sportouch, Catherine; Gahide, Gerald; Finet, Gérard; André-Fouët, Xavier; Revel, Didier; Kirkorian, Gilbert; Monassier, Jean-Pierre; Derumeaux, Geneviève; Ovize, Michel (31 July 2008). "Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction". New England Journal of Medicine. 359 (5): 473–481. doi: 10.1056/NEJMoa071142 . PMID   18669426.
  15. 1 2 Javadov, Sabzali; Karmazyn, Morris (2007). "Mitochondrial Permeability Transition Pore Opening as an Endpoint to Initiate Cell Death and as a Putative Target for Cardioprotection". Cellular Physiology and Biochemistry. 20 (1–4): 1–22. doi: 10.1159/000103747 . PMID   17595511. S2CID   1949575.
  16. 1 2 Cung, Thien-Tri; Morel, Olivier; Cayla, Guillaume; Rioufol, Gilles; Garcia-Dorado, David; Angoulvant, Denis; Bonnefoy-Cudraz, Eric; Guérin, Patrice; Elbaz, Meier; Delarche, Nicolas; Coste, Pierre; Vanzetto, Gerald; Metge, Marc; Aupetit, Jean-François; Jouve, Bernard; Motreff, Pascal; Tron, Christophe; Labeque, Jean-Noel; Steg, Philippe Gabriel; Cottin, Yves; Range, Grégoire; Clerc, Jérome; Claeys, Marc J.; Coussement, Patrick; Prunier, Fabrice; Moulin, Frédéric; Roth, Olivier; Belle, Loïc; Dubois, Philippe; Barragan, Paul; Gilard, Martine; Piot, Christophe; Colin, Patrice; De Poli, Fabien; Morice, Marie-Claude; Ider, Omar; Dubois-Randé, Jean-Luc; Unterseeh, Thierry; Le Breton, Hervé; Béard, Thierry; Blanchard, Didier; Grollier, Gilles; Malquarti, Vincent; Staat, Patrick; Sudre, Arnaud; Elmer, Eskil; Hansson, Magnus J.; Bergerot, Cyrille; Boussaha, Inesse; Jossan, Claire; Derumeaux, Geneviève; Mewton, Nathan; Ovize, Michel (10 September 2015). "Cyclosporine before PCI in Patients with Acute Myocardial Infarction". New England Journal of Medicine. 373 (11): 1021–1031. doi: 10.1056/NEJMoa1505489 . hdl: 10044/1/41761 . PMID   26321103.
  17. ↑ Ottani, Filippo; Latini, Roberto; Staszewsky, Lidia; La Vecchia, Luigi; Locuratolo, Nicola; Sicuro, Marco; Masson, Serge; Barlera, Simona; Milani, Valentina; Lombardi, Mario; Costalunga, Alessandra; Mollichelli, Nadia; Santarelli, Andrea; De Cesare, Nicoletta; Sganzerla, Paolo; Boi, Alberto; Maggioni, Aldo Pietro; Limbruno, Ugo (February 2016). "Cyclosporine A in Reperfused Myocardial Infarction". Journal of the American College of Cardiology. 67 (4): 365–374. doi: 10.1016/j.jacc.2015.10.081 . PMID   26821623. S2CID   205575155.
  18. 1 2 Hausenloy, Derek J.; Yellon, Derek M. (31 July 2008). "Time to Take Myocardial Reperfusion Injury Seriously". New England Journal of Medicine. 359 (5): 518–520. doi:10.1056/NEJMe0803746. PMID   18669431.
  19. ↑ Sullivan, Patrick G.; Sebastian, Andrea H.; Hall, Edward D. (February 2011). "Therapeutic Window Analysis of the Neuroprotective Effects of Cyclosporine A after Traumatic Brain Injury". Journal of Neurotrauma. 28 (2): 311–318. doi:10.1089/neu.2010.1646. PMC   3037811 . PMID   21142667.
  20. ↑ Le Lamer, Sophie; Paradis, Stéphanie; Rahmouni, Hidayat; Chaimbault, Corinne; Michaud, Magali; Culcasi, Marcel; Afxantidis, Jean; Latreille, Mathilde; Berna, Patrick; Berdeaux, Alain; Pietri, Sylvia; Morin, Didier; Donazzolo, Yves; Abitbol, Jean-Louis; Pruss, Rebacca M; Schaller, Sophie (December 2014). "Translation of TRO40303 from myocardial infarction models to demonstration of safety and tolerance in a randomized Phase I trial". Journal of Translational Medicine. 12 (1): 38. doi: 10.1186/1479-5876-12-38 . PMC   3923730 . PMID   24507657.
  21. ↑ van der Spoel, T. I. G.; Jansen of Lorkeers, S. J.; Agostoni, P.; van Belle, E.; Gyongyosi, M.; Sluijter, J. P. G.; Cramer, M. J.; Doevendans, P. A.; Chamuleau, S. A. J. (1 September 2011). "Human relevance of pre-clinical studies in stem cell therapy: systematic review and meta-analysis of large animal models of ischaemic heart disease". Cardiovascular Research. 91 (4): 649–658. doi: 10.1093/cvr/cvr113 . PMID   21498423.
  22. ↑ Zhao, Jing-Jie; Liu, Jun-Li; Liu, Ling; Jia, Hong-Ying (January 2014). "Protection of mesenchymal stem cells on acute kidney injury". Molecular Medicine Reports. 9 (1): 91–96. doi: 10.3892/mmr.2013.1792 . PMID   24220681.
  23. ↑ Jiang, Yuhang; Arounleut, Phonepasong; Rheiner, Steven; Bae, Younsoo; Kabanov, Alexander V.; Milligan, Carol; Manickam, Devika S. (2016-06-10). "SOD1 nanozyme with reduced toxicity and MPS accumulation". Journal of Controlled Release. Thirteenth International Nanomedicine and Drug Delivery Symposium. 231: 38–49. doi:10.1016/j.jconrel.2016.02.038. PMID   26928528.
  24. ↑ Jiang, Yuhang; Brynskikh, Anna M.; S-Manickam, Devika; Kabanov, Alexander V. (2015-09-10). "SOD1 nanozyme salvages ischemic brain by locally protecting cerebral vasculature". Journal of Controlled Release. 213: 36–44. doi:10.1016/j.jconrel.2015.06.021. PMC   4684498 . PMID   26093094.
  25. ↑ Paiva, Marta; Riksen, Niels P; Davidson, Sean M; Hausenloy, Derek J; Monteiro, Pedro; Gonçalves, Lino; Providência, Luís; Rongen, Gerard A; Smits, Paul; Mocanu, Mihaela M; Yellon, Derek M (May 2009). "Metformin Prevents Myocardial Reperfusion Injury by Activating the Adenosine Receptor". Journal of Cardiovascular Pharmacology. 53 (5): 373–378. doi:10.1097/FJC.0b013e31819fd4e7. PMID   19295441. S2CID   21161059.
  26. ↑ Bhamra, Gurpreet S.; Hausenloy, Derek J.; Davidson, Sean M.; Carr, Richard D.; Paiva, Marta; Wynne, Abigail M.; Mocanu, Mihaela M.; Yellon, Derek M. (May 2008). "Metformin protects the ischemic heart by the Akt-mediated inhibition of mitochondrial permeability transition pore opening". Basic Research in Cardiology. 103 (3): 274–284. doi:10.1007/s00395-007-0691-y. PMID   18080084. S2CID   28815693.
  27. ↑ Ten, Vadim; Galkin, Alexander (October 2019). "Mechanism of mitochondrial complex I damage in brain ischemia/reperfusion injury. A hypothesis". Molecular and Cellular Neuroscience. 100: 103408. doi:10.1016/j.mcn.2019.103408. PMID   31494262. S2CID   201835094.
  28. ↑ Bátkai, Sándor; Mukhopadhyay, Partha; Horváth, Bėla; Rajesh, Mohanraj; Gao, Rachel Y; Mahadevan, Anu; Amere, Mukkanti; Battista, Natalia; Lichtman, Aron H; Gauson, Lisa A; Maccarrone, Mauro; Pertwee, Roger G; Pacher, Pál (April 2012). "Δ8-Tetrahydrocannabivarin prevents hepatic ischaemia/reperfusion injury by decreasing oxidative stress and inflammatory responses through cannabinoid CB2 receptors: Δ8-Tetrahydrocannabivarin for reperfusion injury". British Journal of Pharmacology. 165 (8): 2450–2461. doi:10.1111/j.1476-5381.2011.01410.x. PMC   3423240 . PMID   21470208.
  29. ↑ Mukhopadhyay, Partha; Rajesh, Mohanraj; Horváth, Béla; Bátkai, Sándor; Park, Ogyi; Tanchian, Galin; Gao, Rachel Y.; Patel, Vivek; Wink, David A.; Liaudet, Lucas; Haskó, György; Mechoulam, Raphael; Pacher, Pál (May 2011). "Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death". Free Radical Biology and Medicine. 50 (10): 1368–1381. doi:10.1016/j.freeradbiomed.2011.02.021. PMC   3081988 . PMID   21362471.
  30. ↑ Dark, J (2005). "Annual lipid cycles in hibernators: integration of physiology and behavior". Annual Review of Nutrition. 25: 469–97. doi:10.1146/annurev.nutr.25.050304.092514. PMID   16011475.
  31. ↑ Andrews, MT (May 2007). "Advances in molecular biology of hibernation in mammals". BioEssays. 29 (5): 431–40. doi:10.1002/bies.20560. PMID   17450592. S2CID   22894246.
  32. ↑ Kurtz, Courtney C.; Lindell, Susanne L.; Mangino, Martin J.; Carey, Hannah V. (November 2006). "Hibernation confers resistance to intestinal ischemia-reperfusion injury". American Journal of Physiology. Gastrointestinal and Liver Physiology. 291 (5): G895–G901. doi:10.1152/ajpgi.00155.2006. PMID   16751173.
  33. ↑ Zingarelli, Basilia; Hake, Paul W.; O’Connor, Michael; Burroughs, Timothy J.; Wong, Hector R.; Solomkin, Joseph S.; Lentsch, Alex B. (June 2009). "Lung injury after hemorrhage is age dependent: Role of peroxisome proliferator-activated receptor γ". Critical Care Medicine. 37 (6): 1978–1987. doi:10.1097/CCM.0b013e31819feb4d. PMC   2765201 . PMID   19384226.
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