Reperfusion injury 655995 222918419 2008-07-01T19:05:21Z DOI bot 6652755 Citation maintenance. Formatted: journal. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. '''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. ==Mechanisms of reperfusion injury== 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 <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" />. 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 | pmid=15147994 | doi=10.1016/S0002-9610(03)00306-4}}</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" />. In prolonged ischemia (60 minutes or more), [[hypoxanthine]] is formed as breakdown product of [[Adenosine triphosphate|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]] [[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]]. ==Treatment== [[Glisodin]], a [[dietary supplement]] derived from [[superoxide dismutase]] (SOD) and wheat [[gliadin]], has been studied for its ability to mitigate [[ischemia]]-reperfusion injury.{{Fact|date=June 2008}} A study of [[aortic cross-clamping]], a common procedure in [[cardiac surgery]], demonstrated a strong potential benefit with further research ongoing.{{Fact|date=June 2008}} ===Therapeutic Hypothermia=== An intriguing area of research demonstrates the ability of a reduction in body temperature to limit reperfusion injuries. This procedure is called [[therapeutic hypothermia]]. 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.<ref name="Newsweek">Adler, Jerry. “Back From the Dead.” Newsweek. July 23, 2007. </ref> 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.<ref>Polderman, Kees H. “Application of therapeutic hypothermia in the ICU.” Intensive Car Med. (2004) 30:556-575.</ref> ==See also== * [[Ischemia]] * [[Therapeutic hypothermia]] * [[Myocardial_infarction#Reperfusion|Myocardial infarction -- Reperfusion]] ==References== <div class="references-small"> <!--See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for an explanation of how to generate footnotes using the <ref(erences/)> tags--> <references/> </div> ==External links== * [http://www.benbest.com/cryonics/ischemia.html#reperfuse Reperfusion Injury and "No Reflow"] * [http://www.newsweek.com/id/35045 Docs Change the Way They Think About Death] [[Category:Physiology]] [[Category:Neurotrauma]] [[de:Reperfusionsschaden]]