From the Guidelines
Reperfusion injury has severe consequences, including oxidative stress, calcium overload, and activation of inflammatory pathways, which can lead to cell death, microvascular damage, and remote organ damage, emphasizing the need for effective reperfusion strategies to minimize these harmful effects. The consequences of reperfusion injury are multifaceted and can have a significant impact on morbidity, mortality, and quality of life. According to the 2017 study by the European Society of Cardiology Working Group on Cellular Biology of the Heart 1, despite advances in treatment, mortality and morbidity following ST-segment elevation myocardial infarction (STEMI) remain significant, with 7% death and 22% heart failure hospitalization at 1 year.
The harmful consequences of reperfusion injury include:
- Oxidative stress from reactive oxygen species that damage cell membranes and proteins
- Calcium overload within cells that disrupts normal cellular function
- Activation of inflammatory pathways that cause local and systemic inflammation
- Microvascular damage, leading to increased permeability, edema, and potential no-reflow phenomenon
- Cell death pathways, resulting in both necrosis and apoptosis
- Systemic effects, including remote organ damage, particularly affecting the lungs, kidneys, and liver
Clinically, reperfusion injury manifests as arrhythmias, myocardial stunning, and potential infarct expansion in cardiac settings, while in other organs it can cause functional impairment and tissue necrosis. The 2011 ACCF/AHA guideline for coronary artery bypass graft surgery 1 highlights the uncertainty of prophylactic pharmacological therapies or controlled reperfusion strategies aimed at inducing preconditioning or attenuating the adverse consequences of myocardial reperfusion injury. However, the 2017 study by the European Society of Cardiology Working Group on Cellular Biology of the Heart 1 suggests that novel cardioprotective strategies, such as remote ischemic conditioning, may be effective in reducing the detrimental effects of acute myocardial ischemia/reperfusion injury.
Therefore, effective reperfusion strategies, such as remote ischemic conditioning, should be considered to minimize the harmful consequences of reperfusion injury and improve clinical outcomes in patients with ischemic heart disease. The discovery of ischemic preconditioning and its evolution into remote ischemic conditioning has provided a powerful endogenous strategy for cardioprotection, and its translation into the clinical setting may improve patient outcomes.
From the Research
Consequences of Reperfusion Injury
- Reperfusion injury can cause tissue damage due to ischemia, with severe cases potentially resulting in multiorgan failure 2.
- The injury is more severe than the previous injury referred to as ischemia-reperfusion injury, and is a major cause of mortality in the case of ischemic diseases 3.
- Reperfusion injury can arise when a target blood vessel is revascularized, particularly during severe stages of ischemia 2.
- Reperfusion of ischemic areas, in particular the readmission of oxygen, may contribute to further tissue damage (reperfusion injury) 4.
Clinical Manifestations
- Reperfusion injury may lead to myocardial infarction, cardiac arrhythmias, and contractile dysfunction 5.
- Elevated levels of aspartate aminotransferase, alanine transaminase, creatine phosphokinase, and lactate dehydrogenase can be observed in patients with reperfusion injury 2.
- Reperfusion injury and cytokine storm sometimes exhibit similar clinical features, necessitating specific treatment in severe cases 2.
Therapeutic Options
- Several therapies, such as anti-platelets, anti-thrombolytic agents have been developed to contain ischemia-reperfusion injury, but with limited success 3.
- Conditioning techniques such as preconditioning and postconditioning have been used by clinicians to overcome ischemia-reperfusion injury 3, 5.
- Plasmapheresis may represent an effective treatment option in cases of severe progression of reperfusion injury or cytokine storm 2.
- Hypothermia, intraarterial flushing, and preconditioning are also being explored as potential treatments for reperfusion injury 6.