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Stroke Nov 2020
Topics: Brain Ischemia; Humans; Ischemic Stroke; Reperfusion; Stroke; Thrombectomy; United States
PubMed: 33081603
DOI: 10.1161/STROKEAHA.120.032358 -
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 -
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 -
Angiologiia I Sosudistaia Khirurgiia =... 2020Reperfusion syndrome is a complex series of clinical manifestations resulting from restoration of blood flow to previously ischaemic tissues. It is accompanied by damage... (Review)
Review
Reperfusion syndrome is a complex series of clinical manifestations resulting from restoration of blood flow to previously ischaemic tissues. It is accompanied by damage to cells, tissues and organs at various levels, followed by the development of multiple organ failure. This review deals with the main pathophysiological mechanisms of the development of reperfusion syndrome in lesions of cardiac, cerebral and lower-limb vessels. Oxidative stress is considered to be the most important marker of ischaemia-reperfusion injury irrespective of the type of tissues affected. Presented herein are the data on contemporary possibilities of influencing various stages and components of the development of reperfusion injury by means of drug therapy, demonstrating that due to the importance of oxidative stress as a key link of reperfusion injury, antioxidant therapy should be the main component of prevention and treatment of reperfusion injury.
Topics: Antioxidants; Humans; Ischemia; Oxidative Stress; Reperfusion; Reperfusion Injury
PubMed: 33332321
DOI: 10.33529/ANGIO2020421 -
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 -
Neuron May 2024Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals...
Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet-unknown functions. We applied laser speckle imaging, ultrafast ultrasound, and two-photon microscopy in a thrombin-based mouse model of stroke and fibrinolytic treatment to show that LMCs maintain cerebral autoregulation and allow for gradual reperfusion, resulting in small infarcts. In mice with poor LMCs, distal arterial segments collapse, and deleterious hyperemia causes hemorrhage and mortality after recanalization. In silico analyses confirm the relevance of LMCs for preserving perfusion in the ischemic region. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion and preventing futile recanalization after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for beneficial reperfusion after stroke.
Topics: Animals; Ischemic Stroke; Mice; Collateral Circulation; Humans; Reperfusion; Meninges; Male; Cerebrovascular Circulation; Mice, Inbred C57BL; Disease Models, Animal; Brain; Thrombectomy
PubMed: 38412858
DOI: 10.1016/j.neuron.2024.01.031 -
Stroke Oct 2021Reperfusion therapy with intravenous alteplase and endovascular therapy are effective treatments for selected patients with acute ischemic stroke. Guidelines for... (Review)
Review
Reperfusion therapy with intravenous alteplase and endovascular therapy are effective treatments for selected patients with acute ischemic stroke. Guidelines for treatment are based upon randomized trials demonstrating substantial treatment effects for highly selected patients based on time from stroke onset and imaging features. However, patients beyond the current established guidelines might benefit with lesser but still clinically significant treatment effects. The STAIR (Stroke Treatment Academic Industry Roundtable) XI meeting convened a workgroup to consider the "outer limits" of reperfusion therapy by defining the current boundaries, and exploring optimal parameters and methodology for determining the outer limits. In addition to statistical significance, the minimum clinically important difference should be considered in exploring the limits of reperfusion therapy. Societal factors and quality of life considerations should be incorporated into assessment of treatment efficacy. The threshold for perception of benefit in the medical community may differ from that necessary for the Food and Drug Administration approval. Data from alternative sources such as platform trials, registries and large pragmatic trials should supplement randomized controlled trials to improve generalizability to routine clinical practice. Further interactions between industry and academic centers should be encouraged.
Topics: Animals; Endovascular Procedures; Humans; Ischemic Stroke; Reperfusion; Thrombolytic Therapy; Treatment Outcome
PubMed: 34470484
DOI: 10.1161/STROKEAHA.121.035022 -
Arquivos de Neuro-psiquiatria Dec 2023Over the last three decades, stroke care has undergone significant transformations mainly driven by the introduction of reperfusion therapy and the organization of... (Review)
Review
Over the last three decades, stroke care has undergone significant transformations mainly driven by the introduction of reperfusion therapy and the organization of systems of care. Patients receiving treatment through a well-structured stroke service have a much higher chance of favorable outcomes, thereby decreasing both disability and mortality. In this article, we reviewed the scientific evidence for stroke reperfusion therapy, including thrombolysis and thrombectomy, and its implementation in the public health system in Brazil.
Topics: Humans; Ischemic Stroke; Brain Ischemia; Stroke; Thrombectomy; Thrombolytic Therapy; Reperfusion; Treatment Outcome
PubMed: 38157871
DOI: 10.1055/s-0043-1777721 -
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 -
Chinese Journal of Natural Medicines Sep 2023Acute kidney injury (AKI) is an important factor for the occurrence and development of CKD. The protective effect of dihydroartemisinin on AKI and and reported mechanism...
Acute kidney injury (AKI) is an important factor for the occurrence and development of CKD. The protective effect of dihydroartemisinin on AKI and and reported mechanism have not been reported. In this study, we used two animal models including ischemia-reperfusion and UUO, as well as a high-glucose-stimulated HK-2 cell model, to evaluate the protective effect of dihydroartemisinin on premature senescence of renal tubular epithelial cells in vitro and in vivo. We demonstrated that dihydroartemisinin improved renal aging and renal injury by activating autophagy. In addition, we found that co-treatment with chloroquine, an autophagy inhibitor, abolished the anti-renal aging effect of dihydroartemisinin in vitro. These findings suggested that activation of autophagy/elimination of senescent cell might be a useful strategy to prevent AKI/UUO induced renal tubular senescence and fibrosis.
Topics: Animals; Kidney; Acute Kidney Injury; Ischemia; Reperfusion Injury; Autophagy; Reperfusion
PubMed: 37777318
DOI: 10.1016/S1875-5364(23)60398-X