Reperfusion injury overview: Difference between revisions
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==Overview== | ==Overview== | ||
'''Reperfusion injury''', also known as '''ischemia-reperfusion injury''' ('''IRI''') or '''re-oxygenation injury''', is the [[Tissue (biology)|tissue]] [[damage]] which results from the restoration of blood supply to the tissue after a period of [[ischemia]], [[anoxia]] or [[Hypoxia (medical)|hypoxia]] from different [[Pathology|pathologies]]. During the period of absence of [[blood]] to the [[Tissue (biology)|tissues]] a condition is created in which the resulting [[reperfusion]] will result in [[inflammation]] and [[Oxidative|oxidative damage]] through the involvement of various mechanisms mainly involving [[oxidation]], [[Free radical|free radical formation]] and [[Complement|complement activation]] which ultimately leads to [[Programmed cell death|cell death]], rather than restoration of normal function. | '''Reperfusion injury''', also known as '''ischemia-reperfusion injury''' ('''IRI''') or '''re-oxygenation injury''', is the [[Tissue (biology)|tissue]] [[damage]] which results from the restoration of blood supply to the tissue after a period of [[ischemia]], [[anoxia]] or [[Hypoxia (medical)|hypoxia]] from different [[Pathology|pathologies]]. During the period of absence of [[blood]] to the [[Tissue (biology)|tissues]] a condition is created in which the resulting [[reperfusion]] will result in [[inflammation]] and [[Oxidative|oxidative damage]] through the involvement of various mechanisms mainly involving [[oxidation]], [[Free radical|free radical formation]] and [[Complement|complement activation]] which ultimately leads to [[Programmed cell death|cell death]], rather than restoration of normal function. | ||
Various intracellular or extracellular changes during ischemia leads to increased [[Intracellular calcium-sensing proteins|intracellular calcium]] and [[Adenosine triphosphate|ATP]] depletion that will ultimately land up in the cell death if the ongoing process does not stopped. [[Reperfusion]] forms reactive oxygen species . This leads to Increased [[mitochondrial]] pore permeability, [[Complement|complement activation]] & [[Cytochrome|cytochrome release]], [[inflammation]] and [[edema]] formation, [[Neutrophil]] [[platelet]] adhesion and [[thrombosis]] leading to progressive [[Tissue (biology)|tissue]] death. In [[Heart]] [[reperfusion injury]] is attributed to oxidative stress which in turn leads to [[Cardiac arrhythmia|arrhythmias]], [[Infarction]] and [[Stunned myocardium|Myocardial stunning]]. In case of trauma the resulting restoration of [[blood]] flow to the [[tissue]] after prolonged [[ischemia]] aggravates [[tissue]] damage by either directly causing additional injury or by unmasking the injury sustained during the ischemic period. [[Reperfusion injury]] can occur in any organ of body mainly seen in the [[heart]], [[intestine]], [[kidney]], [[lung]], and [[muscle]], and is due to microvascular damage. | Various intracellular or extracellular changes during ischemia leads to increased [[Intracellular calcium-sensing proteins|intracellular calcium]] and [[Adenosine triphosphate|ATP]] depletion that will ultimately land up in the cell death if the ongoing process does not stopped. [[Reperfusion]] forms reactive oxygen species . This leads to Increased [[mitochondrial]] pore permeability, [[Complement|complement activation]] & [[Cytochrome|cytochrome release]], [[inflammation]] and [[edema]] formation, [[Neutrophil]] [[platelet]] adhesion and [[thrombosis]] leading to progressive [[Tissue (biology)|tissue]] death. In [[Heart]] [[reperfusion injury]] is attributed to oxidative stress which in turn leads to [[Cardiac arrhythmia|arrhythmias]], [[Infarction]] and [[Stunned myocardium|Myocardial stunning]]. In case of trauma the resulting restoration of [[blood]] flow to the [[tissue]] after prolonged [[ischemia]] aggravates [[tissue]] damage by either directly causing additional injury or by unmasking the [[injury]] sustained during the [[ischemic]] period. [[Reperfusion injury]] can occur in any organ of body mainly seen in the [[heart]], [[intestine]], [[kidney]], [[lung]], and [[muscle]], and is due to [[microvascular]] damage. | ||
==Pathophysiology== | ==Pathophysiology== | ||
The component playing a major role in the [[pathophysiology]] of [[Ischemia-reperfusion injury]] is Reactive [[oxygen]] species (ROS) causing damage to [[cellular]] and [[biological membranes]]. [[Neutrophils]] also play an important role in initiating and propagating much of the damage involved in the process of [[Ischemia-reperfusion injury]]. [[Ischemia]] is the phase that precedes the restoration of [[blood]] flow to that organ or tissue, resulting in the built-up of [[xanthine oxidase]] and [[hypoxanthine]] that upon the restoration of blood flow leads to the formation of [[Reactive oxygen species|ROS]]. [[Neutrophils]] also potentiate the effect of [[Ischemia-reperfusion injury]] through [[microvascular injury]] by releasing various [[Proteolytic enzyme|proteolytic enzymes]] and [[Reactive oxygen species|ROS]]. Most of the experimental studies carried out in helping understand the mechanism of [[Ischemia-reperfusion injury|Ischemia reperfusion injury]] are mainly on the cat, dog, and horses. | The component playing a major role in the [[pathophysiology]] of [[Ischemia-reperfusion injury]] is Reactive [[oxygen]] species (ROS) causing damage to [[cellular]] and [[biological membranes]]. [[Neutrophils]] also play an important role in initiating and propagating much of the damage involved in the process of [[Ischemia-reperfusion injury]]. [[Ischemia]] is the phase that precedes the restoration of [[blood]] flow to that organ or [[tissue]], resulting in the built-up of [[xanthine oxidase]] and [[hypoxanthine]] that upon the restoration of [[blood]] flow leads to the formation of [[Reactive oxygen species|ROS]]. [[Neutrophils]] also potentiate the effect of [[Ischemia-reperfusion injury]] through [[microvascular injury]] by releasing various [[Proteolytic enzyme|proteolytic enzymes]] and [[Reactive oxygen species|ROS]]. Most of the experimental studies carried out in helping understand the mechanism of [[Ischemia-reperfusion injury|Ischemia reperfusion injury]] are mainly on the [[cat]], [[dog]], and [[horses]]. | ||
==Risk Factors== | ==Risk Factors== | ||
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==Natural History, Complications and Prognosis== | ==Natural History, Complications and Prognosis== | ||
[[Reperfusion injury]] mechanism is mostly studied by scientists in cats and dogs with the first experimental study done in 1955 by Sewell and later different studies were done to understand more about the [[reperfusion injury]] mechanisms. Most of the [[complications]] associated with [[reperfusion injury]] are mainly due to the formation of [[reactive oxygen species]] and [[neutrophil]] activation ultimately resulting in [[tissue]] damage-causing [[Ischemia]], [[Infarction]], [[Haemorrhage]], and [[edema]]. Prognosis, in general, is poor with Ischemia-reperfusion injury resulting in tissue injury and damage. The most important determinant of prognosis is the time taken to reperfuse the [[ischemic tissue]]. More the delay in time to [[reperfusion]], worse the prognosis is. | [[Reperfusion injury]] mechanism is mostly studied by scientists in [[cats]] and [[dogs]] with the first experimental study done in 1955 by Sewell and later different studies were done to understand more about the [[reperfusion injury]] mechanisms. Most of the [[complications]] associated with [[reperfusion injury]] are mainly due to the formation of [[reactive oxygen species]] and [[neutrophil]] activation ultimately resulting in [[tissue]] damage-causing [[Ischemia]], [[Infarction]], [[Haemorrhage]], and [[edema]]. Prognosis, in general, is poor with Ischemia-reperfusion injury resulting in tissue injury and damage. The most important determinant of prognosis is the time taken to reperfuse the [[ischemic tissue]]. More the delay in time to [[reperfusion]], worse the prognosis is. | ||
==Medical Therapy== | ==Medical Therapy== | ||
Revision as of 01:42, 24 August 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]
Overview
Reperfusion injury, also known as ischemia-reperfusion injury (IRI) or re-oxygenation injury, is the tissue damage which results from the restoration of blood supply to the tissue after a period of ischemia, anoxia or hypoxia from different pathologies. During the period of absence of blood to the tissues a condition is created in which the resulting reperfusion will result in inflammation and oxidative damage through the involvement of various mechanisms mainly involving oxidation, free radical formation and complement activation which ultimately leads to cell death, rather than restoration of normal function. Various intracellular or extracellular changes during ischemia leads to increased intracellular calcium and ATP depletion that will ultimately land up in the cell death if the ongoing process does not stopped. Reperfusion forms reactive oxygen species . This leads to Increased mitochondrial pore permeability, complement activation & cytochrome release, inflammation and edema formation, Neutrophil platelet adhesion and thrombosis leading to progressive tissue death. In Heart reperfusion injury is attributed to oxidative stress which in turn leads to arrhythmias, Infarction and Myocardial stunning. In case of trauma the resulting restoration of blood flow to the tissue after prolonged ischemia aggravates tissue damage by either directly causing additional injury or by unmasking the injury sustained during the ischemic period. Reperfusion injury can occur in any organ of body mainly seen in the heart, intestine, kidney, lung, and muscle, and is due to microvascular damage.
Pathophysiology
The component playing a major role in the pathophysiology of Ischemia-reperfusion injury is Reactive oxygen species (ROS) causing damage to cellular and biological membranes. Neutrophils also play an important role in initiating and propagating much of the damage involved in the process of Ischemia-reperfusion injury. Ischemia is the phase that precedes the restoration of blood flow to that organ or tissue, resulting in the built-up of xanthine oxidase and hypoxanthine that upon the restoration of blood flow leads to the formation of ROS. Neutrophils also potentiate the effect of Ischemia-reperfusion injury through microvascular injury by releasing various proteolytic enzymes and ROS. Most of the experimental studies carried out in helping understand the mechanism of Ischemia reperfusion injury are mainly on the cat, dog, and horses.
Risk Factors
Ischemia reperfusion injury is a complex disorder associated with various cardiovascular and other risk factors mainly including Hypertension, hyperlipidemia, Diabetes, Insulin resistance, aging, and defects with coronary artery circulation. Although the exact mechanism about how these causes injuries are still not clear but studies have done so far best explains their role in mediating oxidative stress and endothelial cell dysfunctions, the two most important pathophysiological processes involved in the mediation of injury.
Natural History, Complications and Prognosis
Reperfusion injury mechanism is mostly studied by scientists in cats and dogs with the first experimental study done in 1955 by Sewell and later different studies were done to understand more about the reperfusion injury mechanisms. Most of the complications associated with reperfusion injury are mainly due to the formation of reactive oxygen species and neutrophil activation ultimately resulting in tissue damage-causing Ischemia, Infarction, Haemorrhage, and edema. Prognosis, in general, is poor with Ischemia-reperfusion injury resulting in tissue injury and damage. The most important determinant of prognosis is the time taken to reperfuse the ischemic tissue. More the delay in time to reperfusion, worse the prognosis is.
Medical Therapy
The most common myth about the ischemia-reperfusion injury is itself related to blood flow. One can easily think like if everything is happening due to ischemia and with the restoration of blood flow, the injury should heal. Here is the trick, reperfusion in turn further exacerbates the injury mainly due to the formation of free radicals. There are few approaches that are studied widely and do play a major role in controlling the injury related to ischemia-reperfusion injury
- Prevent generation of free radicals( Oxidative stress) or Increase the tissue's capacity to trap the free radicals
- Controlling the neutrophil activation and infiltration of ischemic tissue
- Hypoxic pre-conditioning
Hyperbaric oxygen therapy is also studied widely and best suited when used within 6 hrs of hypoxia as it helps in the reduction of local and systemic hypoxia and in turn, increases the survival of affected tissue.
Future or Investigational therapies
A lot of studies done in the past three decades helped a lot in understanding the molecular mechanisms associated with Ischemia-reperfusion injury. Also, these studies helped in evaluating various strategies to decrease the incidence and severity associated with Ischemia-reperfusion injury. Existing therapies for Ischemia-reperfusion injury can be divided into Pharmacological and non-pharmacological interventions. A lot of promising studies and clinical trials are still under the pipeline. Till the date, the most encouraging results are associated with ischemic preconditioning and postconditioning, adenosine, and exenatide. A lot of studies have demonstrated the combined effect of pharmacological and nonpharmacological approach as together to be used as a multifactorial approach to improve the clinical outcomes.