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Cerebrovascular Diseases (Basel,... 2021The concept of the ischemic penumbra was defined over 40 years ago by Lindsay Symon and his group and is now an established principle of all acute ischemic stroke... (Review)
Review
The concept of the ischemic penumbra was defined over 40 years ago by Lindsay Symon and his group and is now an established principle of all acute ischemic stroke therapies. These reperfusion treatments rescue threatened, critically hypoperfused brain tissue and have been proven to improve clinical outcomes. We have been fortunate to have observed and played a small part in the penumbral story from its beginnings in the 1970s to its pivotal position today. Over this period, we have witnessed penumbral imaging evolve from positron emission tomography through to magnetic resonance imaging and now predominantly computed tomography perfusion, with the advent of automated imaging facilitating case selection for reperfusion therapies. We and others have conducted clinical trials using penumbral imaging to extend the time window for intravenous thrombolysis and select patients for thrombectomy. Together with the concept of fast- and slow-growing ischemic infarct patterns, this embeds the penumbral principle in everyday clinical management. The opportunity now exists to make penumbral imaging even more portable, affordable, and more widely available using mobile platforms, novel imaging techniques, digital linkage, and artificial intelligence.
Topics: Humans; Ischemic Stroke; Reperfusion
PubMed: 34736251
DOI: 10.1159/000519730 -
Lakartidningen Sep 2023
Topics: Humans; Stroke; Reperfusion
PubMed: 37671948
DOI: No ID Found -
Journal of Neurology, Neurosurgery, and... Feb 2021Investigators acknowledge the limitations of rodent or non-human primate stroke models, hundreds of putative neuroprotectants have been evaluated in preclinical models,... (Review)
Review
Investigators acknowledge the limitations of rodent or non-human primate stroke models, hundreds of putative neuroprotectants have been evaluated in preclinical models, but not one has entered the clinical realm. Initial studies focused on the neuron, but in recent years the focus has widened to also include other neural cells including astrocytes, pericytes and endothelial cells, which together form the neurovascular unit. Some new developments raise renewed hope for neuroprotection: the appearance of new compounds with multiple mechanisms of action, or the promulgation of new standards for a rigorous preclinical testing. At the bedside in the last 5 years, uric acid and nerinetide are the only compounds tested for clinical efficacy in randomised controlled trials (RCTs), where all patients had to receive reperfusion therapies, either intravenous thrombolysis and/or mechanical thrombectomy. In addition, otaplimastat, 3K3A-activated protein C (APC), intra-arterial verapamil and intra-arterial hypothermia were also assessed in combination with reperfusion therapy, but in RCTs that only included feasibility or safety outcomes. Some of these compounds yielded promising results which are discussed in this review. Altogether, a deeper knowledge of the mechanisms involved in the ischaemic death process at the neurovascular unit, an improved preselection and evaluation of drugs at the preclinical stage and the testing of putative neuroprotectants in enriched clinical studies of patients receiving reperfusion therapies, might prove more effective than in the past to reverse a dismal situation that has lasted already too long.
Topics: Humans; Neuroprotection; Neuroprotective Agents; Reperfusion; Stroke; Translational Research, Biomedical
PubMed: 33148815
DOI: 10.1136/jnnp-2020-324283 -
Hamostaseologie May 2018Due to the manifold treatment options for the management of acute pulmonary embolism, state-of-the-art management requires risk stratification for choosing the adapted... (Review)
Review
Due to the manifold treatment options for the management of acute pulmonary embolism, state-of-the-art management requires risk stratification for choosing the adapted treatment for each patient. Reperfusion therapy is an integral part of therapy for patients with pulmonary embolism at high risk for mortality, but its role in patients with intermediate risk pulmonary embolism is more debated. The largest amount of evidence exists for systemic thrombolysis, which is an efficient therapy, but at the prize of an increased bleeding risk. In recent years, various types of catheter-based reperfusion therapies have been introduced, and evidence is growing that this therapy is as efficient as systemic thrombolysis, but with a more favourable safety profile. Surgical embolectomy remains a good alternative for unstable patients, especially for those with absolute contraindications for thrombolysis or after failed systemic thrombolysis. While the early benefits of reperfusion therapy are well documented, evidence for long-term benefit is still scarce. The scope of this review is to summarize the evidence for the currently available reperfusion therapies in the management of acute pulmonary embolism.
Topics: Acute Disease; Catheters; Disease Management; Embolectomy; Humans; Pulmonary Embolism; Reperfusion; Thrombolytic Therapy
PubMed: 29843174
DOI: 10.1055/s-0038-1641717 -
ACS Biomaterials Science & Engineering Dec 2020Ischemia reperfusion (IR)-induced oxidative stress, accompanied by inflammatory responses, contributes to morbidity and mortality in numerous diseases such as acute... (Review)
Review
Ischemia reperfusion (IR)-induced oxidative stress, accompanied by inflammatory responses, contributes to morbidity and mortality in numerous diseases such as acute coronary syndrome, stroke, organ transplantation, and limb injury. Ischemia results in profound hypoxia and tissue dysfunction, whereas subsequent reperfusion further aggravates ischemic tissue damage through inducing cell death and activating inflammatory responses. In this review, we highlight recent studies of therapeutic strategies against IR injury. Furthermore, nanotechnology offers significant improvements in this area. Hence, we also review recent advances in nanomedicines for IR therapy, suggesting them as potent and promising strategies to improve drug delivery to IR-injured tissues and achieve protective effects.
Topics: Drug Delivery Systems; Humans; Nanoparticles; Oxidative Stress; Reperfusion; Reperfusion Injury
PubMed: 33320610
DOI: 10.1021/acsbiomaterials.0c01197 -
Stroke Jun 2021Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients.... (Clinical Trial)
Clinical Trial
BACKGROUND AND PURPOSE
Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke.
METHODS
We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy.
RESULTS
Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528–6.245]).
CONCLUSIONS
In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.
Topics: Aged; Aged, 80 and over; Disease-Free Survival; Endovascular Procedures; Female; Follow-Up Studies; Humans; Male; Mechanical Thrombolysis; Middle Aged; Neoplasms; Registries; Reperfusion; Stroke; Survival Rate
PubMed: 33910369
DOI: 10.1161/STROKEAHA.120.032380 -
Neurotherapeutics : the Journal of the... Apr 2023Racial and ethnic inequities in stroke care are ubiquitous. Acute reperfusion therapies, i.e., IV thrombolysis (IVT) and mechanical thrombectomy (MT), are central to... (Review)
Review
Racial and ethnic inequities in stroke care are ubiquitous. Acute reperfusion therapies, i.e., IV thrombolysis (IVT) and mechanical thrombectomy (MT), are central to acute stroke care and are highly efficacious at preventing death and disability after stroke. Disparities in the use of IVT and MT in the USA are pervasive and contribute to worse outcomes among racial and ethnic minority individuals with ischemic stroke. A meticulous understanding of disparities and underlying root causes is necessary in order to develop targeted mitigation strategies with lasting effects. This review details racial and ethnic disparities in the use of IVT and MT after stroke and highlights inequities in the underlying process measures as well as the contributing root causes. Furthermore, this review spotlights the systemic and structural inequities that contribute to race-based differences in the use of IVT and MT, including geographic and regional differences and differences based on neighborhood, zip code, and hospital type. In addition, recent promising trends suggesting improvements in racial and ethnic IVT and MT disparities and potential approaches for future solutions to achieve equity in stroke care are briefly discussed.
Topics: Humans; Thrombectomy; Ethnicity; Brain Ischemia; Treatment Outcome; Minority Groups; Stroke; Reperfusion
PubMed: 37219714
DOI: 10.1007/s13311-023-01388-y -
Minerva Cardioangiologica Aug 2018Ischemic heart disease remains a leading cause of death worldwide, responsible for an estimated 17.5 million deaths in 2012. Mortality from ST-elevation myocardial... (Review)
Review
Ischemic heart disease remains a leading cause of death worldwide, responsible for an estimated 17.5 million deaths in 2012. Mortality from ST-elevation myocardial infarction STEMI have decreased over the last 3 decades. However, despite the success of reperfusion therapy by primary percutaneous coronary intervention (PPCI) or thrombolysis, STEMI is still of significant concern. A recent patient-level meta-analysis emphasized the pivotal importance of infarct size within 1 month after PPCI as a determinant of all-cause mortality and hospitalization for heart failure at 1 year. Although timely and complete reperfusion is the most effective way of limiting infarct size (IS) and subsequent ventricular remodeling, reperfusion per se adds an additional component of irreversible injury to the myocardium (known as ischemia/reperfusion injury, IRI), and the coronary circulation and it contributes to final infarct size. The prevention and treatment of lethal IRI and coronary microvascular dysfunction pose a continued and formidable barrier to successful myocardial perfusion as opposed to establishing patency of the epicardial infarct-related artery (IRA), and in this context the need for additional cardioprotective strategies to reduce IS and coronary microvascular dysfunction remains the 'last frontier' of reperfusion therapy.
Topics: Cardiotonic Agents; Humans; Myocardial Reperfusion; Myocardial Reperfusion Injury; Percutaneous Coronary Intervention; Postoperative Complications; ST Elevation Myocardial Infarction
PubMed: 29589674
DOI: 10.23736/S0026-4725.18.04680-7 -
Pharmacological Research Nov 2022Reperfusion therapy with recombinant tissue plasminogen activator (rtPA) or mechanical thrombectomy is the most effective treatment for ischemic stroke. However, a large...
Reperfusion therapy with recombinant tissue plasminogen activator (rtPA) or mechanical thrombectomy is the most effective treatment for ischemic stroke. However, a large proportion of stroke patients remain severely disabled even after receiving timely reperfusion therapy. It remains unclear how reperfusion therapy results in secondary injury to the brain tissue and whether different reperfusion therapies induce differential effects. Here, we comprehensively determined the spatiotemporal dynamic changes in brain lipids during the acute phase after reperfusion in a mouse model of transient middle cerebral artery occlusion, with or without rtPA administration, using desorption electrospray ionization (DESI)-mass spectrometry imaging (MSI). Several phospholipids, sphingolipids, and neutral lipids were significantly altered both spatially and temporally at multiple timepoints after reperfusion, many of which were closely associated with expansion of the brain infarction territory and neurological function impairment. Furthermore, rtPA treatment significantly increased brain infarction, cerebral edema, and neurological deficits. Consistently, rtPA treatment caused extensive brain lipid alterations by facilitating brain-wide changes in lipid metabolism and inducing ischemic region-specific lipid changes. Overall, these results provide novel insights into how reperfusion therapy affects brain tissue and the outcome of stroke patients, and thus may facilitate the optimization of the treatment of ischemic stroke.
Topics: Animals; Mice; Tissue Plasminogen Activator; Lipidomics; Brain Ischemia; Reperfusion; Stroke; Infarction, Middle Cerebral Artery; Brain; Ischemic Stroke; Lipid Metabolism; Lipids; Fibrinolytic Agents
PubMed: 36195305
DOI: 10.1016/j.phrs.2022.106482 -
Journal of Cardiovascular Pharmacology... Nov 2021Cardiac reperfusion injury is a well-established outcome following treatment of acute myocardial infarction and other types of ischemic heart conditions. Numerous... (Review)
Review
Cardiac reperfusion injury is a well-established outcome following treatment of acute myocardial infarction and other types of ischemic heart conditions. Numerous cardioprotection protocols and therapies have been pursued with success in pre-clinical models. Unfortunately, there has been lack of successful large-scale clinical translation, perhaps in part due to the multiple pathways that reperfusion can contribute to cell death. The search continues for new cardioprotection protocols based on what has been learned from past results. One class of cardioprotection protocols that remain under active investigation is that of controlled reperfusion. This class consists of those approaches that modify, in a controlled manner, the content of the reperfusate or the mechanical properties of the reperfusate (e.g., pressure and flow). This review article first provides a basic overview of the primary pathways to cell death that have the potential to be addressed by various forms of controlled reperfusion, including no-reflow phenomenon, ion imbalances (particularly calcium overload), and oxidative stress. Descriptions of various controlled reperfusion approaches are described, along with summaries of both mechanistic and outcome-oriented studies at the pre-clinical and clinical phases. This review will constrain itself to approaches that modify endogenously-occurring blood components. These approaches include ischemic postconditioning, gentle reperfusion, controlled hypoxic reperfusion, controlled hyperoxic reperfusion, controlled acidotic reperfusion, and controlled ionic reperfusion. This review concludes with a discussion of the limitations of past approaches and how they point to potential directions of investigation for the future.
Topics: Humans; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Oxidative Stress
PubMed: 34534022
DOI: 10.1177/10742484211046674