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| __NOTOC__ | | __NOTOC__ |
| | {{Reperfusion injury}} |
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| {{SI}} | | {{CMG}} {{AE}} {{AC}} {{Shivam Singla}} |
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| {{EJ}} | | {{SK}} Reperfusion Damage; Damage, Reperfusion; Damages, Reperfusion; Reperfusion Damages; Ischemia-Reperfusion Injury; Ischemia-Reperfusion Injury; Injury, Ischemia-Reperfusion; Injuries, Ischemia-Reperfusion; Injury, Ischemia-Reperfusion; Ischemia-Reperfusion Injuries; Injury, Reperfusion; Injuries, Reperfusion; Reperfusion Injuries |
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| {{CMG}}
| | ==[[Reperfusion injury overview|Overview]]== |
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| ==Overview== | | ==[[Reperfusion injury pathophysiology|Pathophysiology]]== |
| '''Reperfusion injury''' refers to damage to [[tissue (biology)|tissue]] caused when [[blood]] supply returns to the tissue after a period of [[ischemia]]. The absence of [[oxygen]] and [[nutrient]]s from blood creates a condition in which the restoration of [[circulatory system|circulation]] results in [[inflammation]] and [[oxidation|oxidative]] damage through the induction of [[oxidative stress]] rather than restoration of normal function.
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| ==Mechanisms of reperfusion injury== | | ==[[Reperfusion injury risk factors|Risk Factors]]== |
| The damage of reperfusion injury is due in part to the [[inflammatory response]] of damaged tissues. [[White blood cell]]s carried to the area by the newly returning blood release a host of [[cytokine|inflammatory factors]] such as [[interleukin]]s as well as [[reactive oxygen species|free radicals]] in response to tissue damage
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| <ref name="WMClark">{{cite web | last = Clark | first = Wayne M. | title = Reperfusion Injury in Stroke | work = eMedicine | publisher = WebMD | date = January 5, 2005 | url = http://www.emedicine.com/neuro/topic602.htm | accessdate = 2006-08-09 }}</ref>.The restored blood flow reintroduces oxygen within [[cell (biology)|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 build up in small [[capillary|capillaries]], obstructing them and leading to more ischemia<ref name="WMClark" />. Other pathophysiologic disturbances include intracellular calcium overload and the opening of mitochondrial permeability transition pores. <ref name="pmid14962470">{{cite journal |author=Halestrap AP, Clarke SJ, Javadov SA |title=Mitochondrial permeability transition pore opening during myocardial reperfusion--a target for cardioprotection |journal=Cardiovasc. Res. |volume=61 |issue=3 |pages=372–85 |year=2004 |month=February |pmid=14962470 |doi=10.1016/S0008-6363(03)00533-9 |url=http://cardiovascres.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=14962470}}</ref>
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| In prolonged ischemia (60 minutes or more), [[hypoxanthine]] is formed as breakdown product of [[Adenosine triphosphate|ATP]] metabolism. The enzyme ''[[xanthine dehydrogenase]]'' is converted to ''[[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]] [[Radical (chemistry)|radicals]]. Xanthine oxidase also produces [[uric acid]], which may act as both a prooxidant and as a scavenger of reactive species such as peroxinitrite. 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 injury natural history|Natural History, Complications & Prognosis]]== |
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| ==Specific organs affected by reperfusion injury== | | ==Treatment== |
| ===The central nervous system===
| | '''[[Reperfusion injury medical therapy|Medical Therapy]]''' |
| Reperfusion injury plays a part in the [[brain]]'s [[ischemic cascade]], which is involved in [[stroke]] and [[brain trauma]]. Repeated bouts of ischemia and reperfusion injury also are thought to be a factor leading to the formation and failure to [[wound healing|heal]] of [[chronic wound]]s such as [[pressure sore]]s and [[diabetic foot]] [[ulcer]]s<ref name="TMustoe">{{cite journal | author=Mustoe T. | title=Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy | journal=AMERICAN JOURNAL OF SURGERY | volume=187 | issue=5A | year=2004 | pages=65S-70S | id=PMID 15147994}}</ref>. 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]]<ref name="TMustoe" />.
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| ===The myocardium===
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| Restoration of epicardial patency can be associated with reperfusion injury in the myocardium. Many therapies have failed to improve reperfusion injury. Pharmacotherapies that have failed include: <ref name="pmid17306241">{{cite journal |author=Dirksen MT, Laarman GJ, Simoons ML, Duncker DJ |title=Reperfusion injury in humans: a review of clinical trials on reperfusion injury inhibitory strategies |journal=Cardiovasc. Res. |volume=74 |issue=3 |pages=343–55 |year=2007 |month=June |pmid=17306241 |doi=10.1016/j.cardiores.2007.01.014 |url=http://cardiovascres.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=17306241}}</ref>
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| #[[Beta-blockade]]
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| #GIK (glucose-insulin-potassium infusion) (Studied in the Glucose-Insulin-Potassium Infusion in Patients With Acute Myocardial Infarction Without Signs of Heart Failure: The Glucose-Insulin-Potassium Study (GIPS)-II <ref name="pmid16631017">{{cite journal |author=Timmer JR, Svilaas T, Ottervanger JP, ''et al'' |title=Glucose-insulin-potassium infusion in patients with acute myocardial infarction without signs of heart failure: the Glucose-Insulin-Potassium Study (GIPS)-II |journal=J. Am. Coll. Cardiol. |volume=47 |issue=8 |pages=1730–1 |year=2006 |month=April |pmid=16631017 |doi=10.1016/j.jacc.2006.01.040 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(06)00178-1}}</ref>
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| #Sodium-hydrogen exchange inhibitors such as cariporide (Studied in the GUARDIAN <ref name="pmid11120691">{{cite journal |author=Théroux P, Chaitman BR, Danchin N, ''et al'' |title=Inhibition of the sodium-hydrogen exchanger with cariporide to prevent myocardial infarction in high-risk ischemic situations. Main results of the GUARDIAN trial. Guard during ischemia against necrosis (GUARDIAN) Investigators |journal=Circulation |volume=102 |issue=25 |pages=3032–8 |year=2000 |month=December |pmid=11120691 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=11120691}}</ref> <ref name="pmid11714411">{{cite journal |author=Theroux P, Chaitman BR, Erhardt L, ''et al'' |title=Design of a trial evaluating myocardial cell protection with cariporide, an inhibitor of the transmembrane sodium-hydrogen exchanger: the Guard During Ischemia Against Necrosis (GUARDIAN) trial |journal=Curr Control Trials Cardiovasc Med |volume=1 |issue=1 |pages=59–67 |year=2000 |pmid=11714411 |pmc=56207 |doi= |url=http://cvm.controlled-trials.com/content/1/1/59}}</ref> and EXPIDITION <ref name="pmid12691376">{{cite journal |author=Bolli R |title=The role of sodium-hydrogen ion exchange in patients undergoing coronary artery bypass grafting |journal=J Card Surg |volume=18 Suppl 1 |issue= |pages=21–6 |year=2003 |pmid=12691376 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0886-0440&date=2003&volume=18&issue=&spage=21}}</ref> <ref name="pmid18355507">{{cite journal |author=Mentzer RM, Bartels C, Bolli R, ''et al'' |title=Sodium-hydrogen exchange inhibition by cariporide to reduce the risk of ischemic cardiac events in patients undergoing coronary artery bypass grafting: results of the EXPEDITION study |journal=Ann. Thorac. Surg. |volume=85 |issue=4 |pages=1261–70 |year=2008 |month=April |pmid=18355507 |doi=10.1016/j.athoracsur.2007.10.054 |url=http://linkinghub.elsevier.com/retrieve/pii/S0003-4975(07)02183-2}}</ref> trials)
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| #[[Adenosine]] (Studied in the AMISTAD I <ref name="pmid10577561">{{cite journal |author=Mahaffey KW, Puma JA, Barbagelata NA, ''et al'' |title=Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial |journal=J. Am. Coll. Cardiol. |volume=34 |issue=6 |pages=1711–20 |year=1999 |month=November |pmid=10577561 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0735109799004180}}</ref> and AMISTAD II <ref name="pmid15936605">{{cite journal |author=Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW |title=A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II) |journal=J. Am. Coll. Cardiol. |volume=45 |issue=11 |pages=1775–80 |year=2005 |month=June |pmid=15936605 |doi=10.1016/j.jacc.2005.02.061 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(05)00536-X}}</ref> trials)
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| #[[Calcium-channel blockers]]
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| #Potassium–adenosine triphosphate channel openers
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| #Antibodies directed against leukocyte adhesion molecules such as CD 18 (Studied in the LIMIT AMI trial <ref name="pmid11733394">{{cite journal |author=Baran KW, Nguyen M, McKendall GR, ''et al'' |title=Double-blind, randomized trial of an anti-CD18 antibody in conjunction with recombinant tissue plasminogen activator for acute myocardial infarction: limitation of myocardial infarction following thrombolysis in acute myocardial infarction (LIMIT AMI) study |journal=Circulation |volume=104 |issue=23 |pages=2778–83 |year=2001 |month=December |pmid=11733394 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=11733394}}</ref>)
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| #Oxygen free radical scavengers
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| Recent trials, with a monoclonal antibody directed against complement C5 (6) and a protein kinase C inhibitor (7), were disappointing. Adenosine reduced anterior infarct size when used at high doses (8); however, a review of 5 trials (including the AMISTAD [Acute Myocardial Infarction Study of Adenosine] I and II studies) failed to show significant benefit (5). In a report of 2 studies, atrial natriuretic peptide reduced infarct size as estimated by creatine kinase (9). The work in this field has been comprehensively summarized (5). In controlled trials, post-conditioning (10) and cyclosporine (11) reduced infarct size.
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| ==Treatment==
| | '''[[Reperfusion injury future or investigational therapies|Future or Investigational Therapies]]''' |
| [[Glisodin]], a [[dietary supplement]] derived from [[superoxide dismutase]] (SOD) and wheat [[gliadin]], has been studied for its ability to mitigate [[ischemia]]-reperfusion injury. A study of [[aortic cross-clamping]] (a common procedure in [[cardiac surgery]]), demonstrated a strong potential benefit with further research ongoing. | |
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| ==See also== | | ==Related Chapters== |
| * [[Ischemia]] | | * [[Ischemia]] |
| * [[Myocardial_infarction#Reperfusion|Myocardial infarction -- Reperfusion]] | | * [[Myocardial_infarction#Reperfusion|Myocardial infarction -- Reperfusion]] |
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| ==References==
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| <div class="references-small">
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| <!--See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for an explanation of how to generate footnotes using the <ref(erences/)> tags-->
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| <references/>
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| </div>
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| ==External links==
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| * [http://www.benbest.com/cryonics/ischemia.html#reperfuse Reperfusion Injury and "No Reflow"]
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| * [http://www.newsweek.com/id/35045 Docs Change the Way They Think About Death]
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| [[Category:Physiology]] | | [[Category:Physiology]] |
| [[Category:Neurotrauma]] | | [[Category:Neurotrauma]] |
| | [[Category:Cardiology]] |
| | [[Category:Up-To-Date]] |
| | [[Category:Up-To-Date cardiology]] |