Mechanisms of gastrointestinal ischemia-reperfusion injury and potential therapeutic interventions: a review and its implications in the horse.
Abstract: Restoration of blood flow after a period of intestinal ischemia is necessary to maintain cell function and viability; however, the reintroduction of oxygen can initiate a cascade of events that exacerbates tissue injury. Intestinal I-R injury is manifested as increased microvascular and mucosal permeability, and mucosal necrosis. Reperfusion injury begins with the accumulation of hypoxanthine from ATP metabolism and the conversion of XDH to XO during ischemia. Upon reperfusion, the XO catalyzes the conversion of hypoxanthine to superoxide radicals in the presence of oxygen. Superoxide radicals are further reduced to highly reactive hydroxyl radicals, which initiate lipid peroxidation. Lipoperoxidation causes functional and structural alterations in cell membrane lipids and can release numerous inflammatory mediators, which exacerbate tissue damage. Neutrophils are recruited into tissues during ischemia and on reperfusion; then they undergo degranulation and release destructive products (proteases and OFRs), which mediate further tissue injury. A limited number of experimental studies in the gastrointestinal tract of horses have shown I-R injury. Additional studies are necessary to further elucidate and sequence the precise pathophysiologic mechanisms occurring in the equine intestine during I-R. Therapy should be focused on prevention of I-R injury by pharmacologic or chemical inhibition or modification of these pathophysiologic pathways. Selected pharmacologic agents or drug combinations may offer novel, scientifically relevant and yet practical approaches to alleviating intestinal I-R injury in horses. This may improve survival of horses with naturally acquired intestinal strangulation obstruction.
Publication Date: 1995-05-01 PubMed ID: 7674213DOI: 10.1111/j.1939-1676.1995.tb03285.xGoogle Scholar: Lookup
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- Journal Article
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Summary
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This research article discusses how the restoration of blood flow after an episode of intestinal ischemia or blocked blood flow can lead to further tissue damage in the gastrointestinal tract. It explains the series of biochemical processes involved and suggests that therapeutic interventions focused on preventing or modifying these processes could help in treating this condition, particularly in horses.
Overview of Gastrointestinal Ischemia-Reperfusion Injury
- The study first discusses the concept of “reperfusion injury”. It explains that while restoring blood flow after a period of intestinal ischemia is essential for maintaining cell function and survival, the re-introduction of oxygen can actually trigger a chain reaction that worsens tissue damage.
- Intestinal ischemia-reperfusion (I-R) injury can result in increased permeability at both the microvascular and mucosal levels, as well as cause mucosal necrosis or death of the tissue.
Understanding the Biochemical Process
- The reperfusion injury begins with an accumulation of hypoxanthine, a byproduct of ATP metabolism, and the conversion of xanthine dehydrogenase (XDH) to xanthine oxidase (XO) during the ischemic period.
- Upon reperfusion, XO facilitates the conversion of hypoxanthine to superoxide radicals in the presence of oxygen. These superoxide radicals can further be reduced to highly reactive hydroxyl radicals, which lead to lipid peroxidation.
- Lipid peroxidation can cause both functional and structural changes to the cell membrane lipids, in turn releasing a series of inflammatory mediators that intensify tissue damage.
The Role of Neutrophils
- Neutrophils, a type of white blood cell, also play a role in this process. They are recruited into the tissues during ischemia and upon reperfusion, they release destructive products, such as proteases and oxygen free radicals (OFRs), exacerbating the tissue damage.
Implications for Horses
- While only a few experimental studies on horses have demonstrated I-R injury, the authors of this article believe that more research is needed to understand and sequence the precise pathophysiological mechanisms occurring in the equine intestine during I-R.
- The paper suggests that therapy for this condition should focus on the prevention of I-R injury by pharmacological or chemical inhibition or modification of the biochemical pathways involved.
- The authors propose that selected pharmacological agents or combinations of drugs may present novel and scientifically relevant approaches for treating intestinal I-R injury in horses, potentially improving the survival rates of horses with naturally occurring intestinal strangulation obstruction.
Cite This Article
APA
Moore RM, Muir WW, Granger DN.
(1995).
Mechanisms of gastrointestinal ischemia-reperfusion injury and potential therapeutic interventions: a review and its implications in the horse.
J Vet Intern Med, 9(3), 115-132.
https://doi.org/10.1111/j.1939-1676.1995.tb03285.x Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, Ohio State University, Columbus, USA.
MeSH Terms
- Animals
- Gastrointestinal Diseases / physiopathology
- Gastrointestinal Diseases / therapy
- Gastrointestinal Diseases / veterinary
- Horse Diseases / physiopathology
- Horse Diseases / therapy
- Horses
- Reperfusion Injury / physiopathology
- Reperfusion Injury / therapy
- Reperfusion Injury / veterinary
Citations
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