Reperfusion injury: Difference between revisions

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#[[Beta-blockade]]
#[[Beta-blockade]]
#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>
#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>
#Sodium-hydrogen exchange inhibitors such as [[cariporide]] (Studied in the GUARDIAN and EXPIDITION trials)
#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)
#[[Adenosine]] (Studied in the AMISTAD trials)
#[[Adenosine]] (Studied in the AMISTAD trials)
#[[Calcium-channel blockers]]
#[[Calcium-channel blockers]]

Revision as of 15:24, 4 March 2009


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Please Join in Editing This Page and Apply to be an Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]

Overview

Reperfusion injury refers to damage to tissue caused when blood supply returns to the tissue after a period of ischemia. The absence of oxygen and nutrients from blood 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.

Mechanisms of reperfusion injury

The damage of reperfusion injury is due in part to the inflammatory response of damaged tissues. 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 [1].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. Leukocytes may also build up in small capillaries, obstructing them and leading to more ischemia[1]. Other pathophysiologic disturbances include intracellular calcium overload and the opening of mitochondrial permeability transition pores. [2]

In prolonged ischemia (60 minutes or more), hypoxanthine is formed as breakdown product of 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 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.

Specific organs affected by reperfusion injury

The central nervous system

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 heal of chronic wounds such as pressure sores and diabetic foot ulcers[3]. 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[3].

The myocardium

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: [4]

  1. Beta-blockade
  2. 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 [5]
  3. Sodium-hydrogen exchange inhibitors such as cariporide (Studied in the GUARDIAN [6] [7] and EXPIDITION [8] [9] trials)
  4. Adenosine (Studied in the AMISTAD trials)
  5. Calcium-channel blockers
  6. Potassium–adenosine triphosphate channel openers
  7. Antibodies directed against leukocyte adhesion molecules such as CD 18 (Studied in the LIMIT AMI trial)
  8. Oxygen free radical scavengers

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.

Treatment

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.

See also

References

  1. 1.0 1.1 Clark, Wayne M. (January 5, 2005). "Reperfusion Injury in Stroke". eMedicine. WebMD. Retrieved 2006-08-09.
  2. Halestrap AP, Clarke SJ, Javadov SA (2004). "Mitochondrial permeability transition pore opening during myocardial reperfusion--a target for cardioprotection". Cardiovasc. Res. 61 (3): 372–85. doi:10.1016/S0008-6363(03)00533-9. PMID 14962470. Unknown parameter |month= ignored (help)
  3. 3.0 3.1 Mustoe T. (2004). "Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy". AMERICAN JOURNAL OF SURGERY. 187 (5A): 65S–70S. PMID 15147994.
  4. Dirksen MT, Laarman GJ, Simoons ML, Duncker DJ (2007). "Reperfusion injury in humans: a review of clinical trials on reperfusion injury inhibitory strategies". Cardiovasc. Res. 74 (3): 343–55. doi:10.1016/j.cardiores.2007.01.014. PMID 17306241. Unknown parameter |month= ignored (help)
  5. Timmer JR, Svilaas T, Ottervanger JP; et al. (2006). "Glucose-insulin-potassium infusion in patients with acute myocardial infarction without signs of heart failure: the Glucose-Insulin-Potassium Study (GIPS)-II". J. Am. Coll. Cardiol. 47 (8): 1730–1. doi:10.1016/j.jacc.2006.01.040. PMID 16631017. Unknown parameter |month= ignored (help)
  6. Théroux P, Chaitman BR, Danchin N; et al. (2000). "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". Circulation. 102 (25): 3032–8. PMID 11120691. Unknown parameter |month= ignored (help)
  7. Theroux P, Chaitman BR, Erhardt L; et al. (2000). "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". Curr Control Trials Cardiovasc Med. 1 (1): 59–67. PMC 56207. PMID 11714411.
  8. Bolli R (2003). "The role of sodium-hydrogen ion exchange in patients undergoing coronary artery bypass grafting". J Card Surg. 18 Suppl 1: 21–6. PMID 12691376.
  9. Mentzer RM, Bartels C, Bolli R; et al. (2008). "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". Ann. Thorac. Surg. 85 (4): 1261–70. doi:10.1016/j.athoracsur.2007.10.054. PMID 18355507. Unknown parameter |month= ignored (help)

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