-
Animal Models and Experimental Medicine Sep 2021Stroke is a devastating disease with high morbidity and mortality. Animal models are indispensable tools that can mimic stroke processes and can be used for... (Review)
Review
Stroke is a devastating disease with high morbidity and mortality. Animal models are indispensable tools that can mimic stroke processes and can be used for investigating mechanisms and developing novel therapeutic regimens. As a heterogeneous disease with complex pathophysiology, mimicking all aspects of human stroke in one animal model is impossible. Each model has unique strengths and weaknesses. Models such as transient or permanent intraluminal thread occlusion middle cerebral artery occlusion (MCAo) models and thromboembolic models are the most commonly used in simulating human ischemic stroke. The endovascular filament occlusion model is characterized by easy manipulation and accurately controllable reperfusion and is suitable for studying the pathogenesis of focal ischemic stroke and reperfusion injury. Although the reproducibility of the embolic model is poor, it is more convenient for investigating thrombolysis. Rats are the most frequently used animal model for stroke. This review mainly outlines the stroke models of rats and discusses their strengths and shortcomings in detail.
Topics: Animals; Disease Models, Animal; Infarction, Middle Cerebral Artery; Rats; Reperfusion; Reproducibility of Results; Stroke
PubMed: 34557647
DOI: 10.1002/ame2.12179 -
Intensive Care Medicine Apr 2021The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation care...
The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation care guidelines for adults, which are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. The topics covered include the post-cardiac arrest syndrome, diagnosis of cause of cardiac arrest, control of oxygenation and ventilation, coronary reperfusion, haemodynamic monitoring and management, control of seizures, temperature control, general intensive care management, prognostication, long-term outcome, rehabilitation and organ donation.
Topics: Adult; Cardiopulmonary Resuscitation; Critical Care; Heart Arrest; Humans; Myocardial Reperfusion; Resuscitation; Seizures
PubMed: 33765189
DOI: 10.1007/s00134-021-06368-4 -
Journal of Cardiology Feb 2023Owing to recent advances in early reperfusion strategies, pharmacological therapy, standardized care, and the identification of vulnerable patient subsets, the prognosis... (Review)
Review
Owing to recent advances in early reperfusion strategies, pharmacological therapy, standardized care, and the identification of vulnerable patient subsets, the prognosis of acute myocardial infarction has improved. However, there is still considerable room for improvement. This review article summarizes the latest evidence concerning clinical diagnosis and treatment of acute myocardial infarction.
Topics: Humans; Myocardial Infarction; Myocardial Reperfusion; Thrombolytic Therapy; Prognosis; Percutaneous Coronary Intervention; Treatment Outcome; Myocardial Revascularization
PubMed: 35882613
DOI: 10.1016/j.jjcc.2022.07.003 -
European Heart Journal Apr 2023During the last 5-7 years, tremendous progress was achieved in the reperfusion treatment of acute ischaemic stroke during its first few hours from symptom onset. This... (Review)
Review
During the last 5-7 years, tremendous progress was achieved in the reperfusion treatment of acute ischaemic stroke during its first few hours from symptom onset. This review summarizes the latest evidence from randomized clinical trials and prospective registries with a focus on endovascular treatment using stent retrievers, aspiration catheters, thrombolytics, and (in selected patients) carotid stenting. Novel approaches in prehospital (mobile interventional stroke teams) and early hospital (direct transfer to angiography) management are described, and future perspectives ('all-in-one' laboratories with angiography and computed tomography integrated) are discussed. There is reasonable chance for patients with moderate-to-severe acute ischaemic stroke to survive without permanent sequelae when the large-vessel occlusion is removed by means of modern pharmaco-mechanic approach. Catheter thrombectomy is now the golden standard of acute stroke treatment. The role of cardiologists in stroke is expanding from diagnostic help (to reveal the cause of stroke) to acute therapy in those regions where such up-to-date Class I. A treatment is not yet available.
Topics: Humans; Stroke; Brain Ischemia; Prospective Studies; Endovascular Procedures; Thrombectomy; Ischemic Stroke; Stents; Reperfusion; Treatment Outcome
PubMed: 36477996
DOI: 10.1093/eurheartj/ehac684 -
Journal of the American College of... Apr 2015The damage inflicted on the myocardium during acute myocardial infarction is the result of 2 processes: ischemia and subsequent reperfusion (ischemia/reperfusion... (Review)
Review
The damage inflicted on the myocardium during acute myocardial infarction is the result of 2 processes: ischemia and subsequent reperfusion (ischemia/reperfusion injury). During the last 3 decades, therapies to reduce ischemic injury (mainly reperfusion strategies) have been widely incorporated into clinical practice. The remarkable reduction in death rates achieved with these therapies has resulted in a shift in emphasis from efforts to reduce mortality to a focus on tackling the downstream consequence of survival: post-infarction heart failure. Infarct size is the main determinant of long-term mortality and chronic heart failure, and thus, the possibility of limiting the extent of necrosis during an ST-segment elevation myocardial infarction is of great individual and socioeconomic value. After the great success of therapies to reduce ischemic injury, the time has come to focus efforts on therapies to reduce reperfusion injury, but in the recent few years, few interventions have successfully passed the proof-of-concept stage. In this review, we examine the past, present, and future therapies to reduce ischemia/reperfusion injury.
Topics: Animals; Glucagon-Like Peptide 1; Humans; Ischemic Preconditioning, Myocardial; Myocardial Reperfusion; Myocardial Reperfusion Injury; Randomized Controlled Trials as Topic
PubMed: 25857912
DOI: 10.1016/j.jacc.2015.02.032 -
Oxidative Medicine and Cellular... 2021Myocardial ischemia is a disease with high morbidity and mortality, for which reperfusion is currently the standard intervention. However, the reperfusion may lead to... (Review)
Review
Myocardial ischemia is a disease with high morbidity and mortality, for which reperfusion is currently the standard intervention. However, the reperfusion may lead to further myocardial damage, known as myocardial ischemia/reperfusion injury (MI/RI). Oxidative stress is one of the most important pathological mechanisms in reperfusion injury, which causes apoptosis, autophagy, inflammation, and some other damage in cardiomyocytes through multiple pathways, thus causing irreversible cardiomyocyte damage and cardiac dysfunction. This article reviews the pathological mechanisms of oxidative stress involved in reperfusion injury and the interventions for different pathways and targets, so as to form systematic treatments for oxidative stress-induced myocardial reperfusion injury and make up for the lack of monotherapy.
Topics: Humans; Myocardial Ischemia; Oxidative Stress; Reperfusion
PubMed: 34055195
DOI: 10.1155/2021/6614009 -
Nature Reviews. Neurology Apr 2022For over 40 years, attempts to develop treatments that protect neurons and other brain cells against the cellular and biochemical consequences of cerebral ischaemia in... (Review)
Review
For over 40 years, attempts to develop treatments that protect neurons and other brain cells against the cellular and biochemical consequences of cerebral ischaemia in acute ischaemic stroke (AIS) have been unsuccessful. However, the advent of intravenous thrombolysis and endovascular thrombectomy has taken us into a new era of treatment for AIS in which highly effective reperfusion therapy is widely available. In this context, cytoprotective treatments should be revisited as adjunctive treatment to reperfusion therapy. Renewed efforts should focus on developing new drugs that target multiple aspects of the ischaemic cascade, and previously developed drugs should be reconsidered if they produced robust cytoprotective effects in preclinical models and their safety profiles were reasonable in previous clinical trials. Several development pathways for cytoprotection as an adjunct to reperfusion can be envisioned. In this Review, we outline the targets for cytoprotective therapy and discuss considerations for future drug development, highlighting the recent ESCAPE-NA1 trial of nerinetide, which produced the most promising results to date. We review new types of clinical trial to evaluate whether cytoprotective drugs can slow infarct growth prior to reperfusion and/or ameliorate the consequences of reperfusion, such as haemorrhagic transformation. We also highlight how advanced brain imaging can help to identify patients with salvageable ischaemic tissue who are likely to benefit from cytoprotective therapy.
Topics: Brain; Brain Ischemia; Cytoprotection; Endovascular Procedures; Humans; Ischemic Stroke; Reperfusion; Stroke; Thrombectomy; Treatment Outcome
PubMed: 35079135
DOI: 10.1038/s41582-021-00605-6 -
JAMA Sep 2021Mechanical thrombectomy using a stent retriever or contact aspiration is widely used for treatment of patients with acute ischemic stroke due to anterior circulation... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Thrombectomy With Combined Contact Aspiration and Stent Retriever vs Stent Retriever Alone on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion: The ASTER2 Randomized Clinical Trial.
IMPORTANCE
Mechanical thrombectomy using a stent retriever or contact aspiration is widely used for treatment of patients with acute ischemic stroke due to anterior circulation large vessel occlusion, but the additional benefit of combining contact aspiration with stent retriever is uncertain.
OBJECTIVE
To determine whether mechanical thrombectomy for treatment of anterior circulation large vessel occlusion stroke with initial contact aspiration and stent retriever combined results in better final angiographic outcome than with standard stent retriever alone.
DESIGN, SETTING, AND PARTICIPANTS
This trial was a multicenter randomized, open-label, blinded end point evaluation that enrolled 408 patients from October 16, 2017, to May 29, 2018, in 11 French comprehensive stroke centers, with a 12-month outcome follow-up. Patients with a large vessel occlusion in the anterior circulation were included up to 8 hours after symptom onset. The final date of follow-up was June, 19, 2019.
INTERVENTIONS
Patients were randomly assigned (1:1 allocation) to receive initial thrombectomy with contact aspiration and stent retriever combined (205) or stent retriever alone (203).
MAIN OUTCOMES AND MEASURES
The primary outcome was the rate of expanded Thrombolysis In Cerebral Infarction score of 2c or 3 (eTICI 2c/3; ie, scores indicate near-total and total reperfusion grades) at the end of the procedure.
RESULTS
Among the 408 patients who were randomized, 3 were excluded, and 405 (99.3%) patients (mean age, 73 years; 220 [54%] women and 185 [46%] men) were included in the primary analysis. The rate of eTICI 2c/3 at the end of the endovascular procedure was not significantly different between the 2 thrombectomy groups (64.5% [131 of 203 patients] for contact aspiration and stent retriever combined vs 57.9% [117 of 202 patients] for stent retriever alone; risk difference, 6.6% [95% CI, -3.0% to 16.2%]; adjusted odds ratio [OR], 1.33 [95% CI, 0.88 to 1.99]; P = .17). Of 14 prespecified secondary efficacy end points, 12 showed no significant difference. A higher rate of successful reperfusion was achieved in the contact aspiration combined with stent retriever group vs the stent retriever alone group (eTICI 2b50/2c/3, 86.2% vs 72.3%; adjusted OR, 2.54 [95% CI, 1.51 to 4.28]; P < .001) and of near-total or total reperfusion (eTICI 2c/3, 59.6% vs 49.5%; adjusted OR, 1.52 [95% CI, 1.02 to 2.27]; P = .04) after the assigned initial intervention alone.
CONCLUSIONS AND RELEVANCE
Among patients with acute ischemic stroke due to large vessel occlusion, an initial thrombectomy technique consisting of contact aspiration and stent retriever combined, compared with stent retriever alone, did not significantly improve the rate of near-total or total reperfusion (eTICI 2c/3) at the end of the endovascular procedure, although the trial may have been underpowered to detect smaller differences between groups.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03290885.
Topics: Aged; Arterial Occlusive Diseases; Combined Modality Therapy; Device Removal; Female; Humans; Ischemic Stroke; Male; Reperfusion; Stents; Thrombectomy; Treatment Outcome
PubMed: 34581737
DOI: 10.1001/jama.2021.13827 -
Molecular Therapy : the Journal of the... Mar 2022Blood-brain barrier (BBB) damage can be a result of central nervous system (CNS) diseases and may be a cause of CNS deterioration. However, there are still many unknowns...
Blood-brain barrier (BBB) damage can be a result of central nervous system (CNS) diseases and may be a cause of CNS deterioration. However, there are still many unknowns regarding effective and targeted therapies for maintaining BBB integrity during ischemia/reperfusion (I/R) injury. In this study, we demonstrate that the circular RNA of FoxO3 (circ-FoxO3) promotes autophagy via mTORC1 inhibition to attenuate BBB collapse under I/R. Upregulation of circ-FoxO3 and autophagic flux were detected in brain microvessel endothelial cells in patients with hemorrhagic transformation and in mice models with middle cerebral artery occlusion/reperfusion. In vivo and in vitro studies indicated that circ-FoxO3 alleviated BBB damage principally by autophagy activation. Mechanistically, we found that circ-FoxO3 inhibited mTORC1 activity mainly by sequestering mTOR and E2F1, thus promoting autophagy to clear cytotoxic aggregates for improving BBB integrity. These results demonstrate that circ-FoxO3 plays a novel role in protecting against BBB damage, and that circ-FoxO3 may be a promising therapeutic target for neurological disorders associated with BBB damage.
Topics: Animals; Autophagy; Blood-Brain Barrier; Brain Ischemia; Endothelial Cells; Forkhead Box Protein O3; Humans; Infarction, Middle Cerebral Artery; Mechanistic Target of Rapamycin Complex 1; Mice; RNA, Circular; Reperfusion; Reperfusion Injury
PubMed: 34763084
DOI: 10.1016/j.ymthe.2021.11.004 -
Circulation Jul 2017For >4 decades, the holy grail in the treatment of acute myocardial infarction has been the mitigation of lethal injury. Despite promising initial results and decades of... (Review)
Review
For >4 decades, the holy grail in the treatment of acute myocardial infarction has been the mitigation of lethal injury. Despite promising initial results and decades of investigation by the cardiology research community, the only treatment with proven efficacy is early reperfusion of the occluded coronary artery. The remarkable record of failure has led us and others to wonder if cardioprotection is dead. The path to translation, like the ascent to Everest, is certainly littered with corpses. We do, however, highlight a therapeutic principle that provides a glimmer of hope: cellular postconditioning. Administration of cardiosphere-derived cells after reperfusion limits infarct size measured acutely, while providing long-term structural and functional benefits. The recognition that cell therapy may be cardioprotective, and not just regenerative, merits further exploration before we abandon the pursuit entirely.
Topics: Animals; Cell- and Tissue-Based Therapy; Humans; Ischemic Postconditioning; Myocardial Infarction; Myocardial Reperfusion; Myocytes, Cardiac
PubMed: 28674094
DOI: 10.1161/CIRCULATIONAHA.116.027039