Ischaemia-reperfusion injury in the critically ill

2016 ◽  
Author(s):  
Mitchell P. Fink
Keyword(s):  
Solid Organ Transplantation ◽  
Myocardial Damage ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Solid Organ ◽  
Therapeutic Approaches ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
Clinical Conditions ◽  
Ros Scavengers

Ischaemia/reperfusion (I/R) injury contributes to the pathogenesis of many common clinical conditions, including stroke, myocardial damage after percutaneous intervention for acute coronary artery occlusion, primary graft dysfunction after solid organ transplantation. The mechanisms that are responsible for I/R injury remain incompletely understood, but damage caused by reactive oxygen species (ROS) and reactive nitrogen species clearly is important. A number of therapeutic approaches, such as administration of ROS scavengers, are effective in animal models of I/R injury, but for the most part, translation of these findings into strategies that can clearly benefit patients has yet to be achieved.

scholarly journals The mitochondria-targeting peptide elamipretide diminishes circulating HtrA2 in ST-segment elevation myocardial infarction

2017 ◽  
Vol 8 (8) ◽  
pp. 695-702 ◽  
Author(s):  
Marcus Hortmann ◽  
Samuel Robinson ◽  
Moritz Mohr ◽  
Maximillian Mauler ◽  
Daniela Stallmann ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Serum Level ◽  
Reperfusion Injury ◽  
Myocardial Damage ◽  
Artery Occlusion ◽  
Ischaemia Reperfusion Injury ◽  
St Segment Elevation ◽  
Ischaemia Reperfusion ◽  
Targeting Peptide ◽  
Mitochondria Targeting

Background: The extent of myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI) depends on both the time to reperfusion as well as injury induced by ischaemia–reperfusion resulting in a cascade of cellular and humoral reactions. As a consequence of ischaemia–reperfusion in the heart, the high-temperature requirement serine peptidase 2 (HtrA2) is translocated from the mitochondria to the cytosol, whereupon it induces protease activity-dependent apoptosis mediated via caspases. Myocardial damage induced by reperfusion cannot be monitored due to a current lack in specific biomarkers. We examined the serum level of HtrA2 as a potentially novel biomarker for mitochondrial-induced cardiomyocyte apoptosis. Methods: After informed consent, peripheral blood was obtained from patients ( n=19) with first-time acute anterior STEMI after percutaneous coronary intervention. Within this group, 10 of the patients received the mitochondria-targeting peptide elamipretide (phase 2a clinical study EMBRACE (NCT01572909)). Blood was also obtained from a control group of healthy donors ( n=16). The serum level of HtrA2 was measured by an enzyme-linked immunosorbent assay (ELISA). In a murine model of myocardial ischaemia–reperfusion injury, HtrA2 was determined in plasma by ELISA after left anterior descending artery occlusion. Results: HtrA2 median was significantly increased in patients with STEMI compared to healthy controls 392.4 (240.7–502.8) pg/mL vs. 1805.5 (981.3–2220.1) pg/mL ( P⩽0.05). Elamipretide significantly reduced the HtrA2 median serum level after myocardial infarction 1805.5 (981.3–2220.1) pg/mL vs. 496.5 (379.4–703.8) pg/mL ( P⩽0.05). Left anterior descending artery occlusion in mice significantly increased HtrA2 mean in plasma (117.4 fg/ml±SEM 28.1 vs. 525.2 fg/ml±SEM 96; P⩽0.05). Conclusion: Compared to healthy controls, we found significantly increased serum levels of HtrA2 in patients with STEMI. The result was validated in a murine model of myocardial ischaemia–reperfusion injury. In humans the increased serum level was significantly reduced by the mitochondria-targeting peptide elamipretide. In conclusion, HtrA2 is detectable in serum of patients with STEMI and might present a novel biomarker for mitochondrial-induced cardiomyocyte apoptosis. Consequently, HtrA2 may also show promise as a biomarker for the identification of ischaemia–reperfusion injury. However, this must be validated in a lager clinical trial.

An Introduction to Cardioprotection

2011 ◽  
Keyword(s):  
Reperfusion Injury ◽  
Myocardial Injury ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Myocardial Damage ◽  
Myocardial Salvage ◽  
Ischaemia Reperfusion Injury ◽  
Acute Ischaemia ◽  
Ischaemia Reperfusion ◽  
Considerable Morbidity

• In its broadest sense, the term ‘cardioprotection’ encompasses ‘all mechanisms and means that contribute to the preservation of the heart by reducing or even preventing myocardial damage’• However, for the purposes of this book, the term ‘cardioprotection’ will refer to the endogenous mechanisms and therapeutic strategies that reduce or prevent myocardial damage induced by acute ischaemia-reperfusion injury• In this context, cardioprotection begins with the primary prevention of coronary heart disease and includes the reduction of myocardial injury sustained during coronary artery bypass graft surgery, and an acute myocardial infarction, conditions with considerable morbidity and mortality• An understanding of the pathophysiology of acute myocardial ischaemia-reperfusion injury is essential when designing new cardioprotective strategies• Several methods exist for both quantifying myocardial damage induced by acute ischaemia-reperfusion injury and for assessing myocardial salvage following the application of cardioprotective strategies• Importantly, novel cardioprotective strategies must be capable of preventing and reducing myocardial damage over and above that provided by current optimal therapy.

scholarly journals The Immunology of SARS-CoV-2 Infection and Vaccines in Solid Organ Transplant Recipients

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1879
Author(s):  
Dominika Dęborska-Materkowska ◽  
Dorota Kamińska
Keyword(s):  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Cell Mediated Immunity ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Therapeutic Approaches ◽  
Current State ◽  
Severe Infections ◽  
Main Component

Since its outbreak in December 2019, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to an enormous rise in scientific response with an excess of COVID-19-related studies on the pathogenesis and potential therapeutic approaches. Solid organ transplant (SOT) recipients are a heterogeneous population with long-lasting immunosuppression as a joining element. Immunocompromised patients are a vulnerable population with a high risk of severe infections and an increased infection-related mortality rate. It was postulated that the hyperinflammatory state due to cytokine release syndrome during severe COVID-19 could be alleviated by immunosuppressive therapy in SOT patients. On the other hand, it was previously established that T cell-mediated immunity, which is significantly weakened in SOT recipients, is the main component of antiviral immune responses. In this paper, we present the current state of science on COVID-19 immunology in relation to solid organ transplantation with prospective therapeutic and vaccination strategies in this population.

Effects of propranolol on myocardial damage resulting from coronary artery occlusion followed by reperfusion

1986 ◽  
Vol 111 (3) ◽  
pp. 519-524 ◽  
Author(s):  
Kozui Miyazawa ◽  
Haru Fukuyama ◽  
Eiichi Komatsu ◽  
Ichiro Yamaguchi
Keyword(s):  
Coronary Artery ◽  
Myocardial Damage ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion

scholarly journals Characterization of a novel model of global forebrain ischaemia–reperfusion injury in mice and comparison with focal ischaemic and haemorrhagic stroke

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Natasha Ting Lee ◽  
Carly Selan ◽  
Joanne S. J. Chia ◽  
Sharelle A. Sturgeon ◽  
David K. Wright ◽  
...  
Keyword(s):  
Blood Flow ◽  
Haemorrhagic Stroke ◽  
Artery Occlusion ◽  
Ischaemia Reperfusion Injury ◽  
Artery Ligation ◽  
Ischaemic Injury ◽  
Ischaemia Reperfusion ◽  
Inflammatory Chemokines ◽  
Apoptotic Activity ◽  
Global Brain Ischaemia

Abstract Stroke is caused by obstructed blood flow (ischaemia) or unrestricted bleeding in the brain (haemorrhage). Global brain ischaemia occurs after restricted cerebral blood flow e.g. during cardiac arrest. Following ischaemic injury, restoration of blood flow causes ischaemia–reperfusion (I/R) injury which worsens outcome. Secondary injury mechanisms after any stroke are similar, and encompass inflammation, endothelial dysfunction, blood–brain barrier (BBB) damage and apoptosis. We developed a new model of transient global forebrain I/R injury (dual carotid artery ligation; DCAL) and compared the manifestations of this injury with those in a conventional I/R injury model (middle-cerebral artery occlusion; MCAo) and with intracerebral haemorrhage (ICH; collagenase model). MRI revealed that DCAL produced smaller bilateral lesions predominantly localised to the striatum, whereas MCAo produced larger focal corticostriatal lesions. After global forebrain ischaemia mice had worse overall neurological scores, although quantitative locomotor assessment showed MCAo and ICH had significantly worsened mobility. BBB breakdown was highest in the DCAL model while apoptotic activity was highest after ICH. VCAM-1 upregulation was specific to ischaemic models only. Differential transcriptional upregulation of pro-inflammatory chemokines and cytokines and TLRs was seen in the three models. Our findings offer a unique insight into the similarities and differences in how biological processes are regulated after different types of stroke. They also establish a platform for analysis of therapies such as endothelial protective and anti-inflammatory agents that can be applied to all types of stroke.

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