cardiovascular-agents and Brain-Ischemia

Stroke is a leading cause of adult mortality and disability worldwide. Extracranial atherosclerotic disease (ECAD), primarily, carotid artery stenosis, accounts for approximately 18%-25% of ischaemic stroke. Recent advances in neuroimaging, medical therapy and interventional management have led to A significant reduction of stroke from carotid artery stenosis. The current treatment of ECAD includes optimal medical therapy, carotid endarterectomy (CEA) and carotid artery stenting (CAS). The selection of treatments depends on symptomatic status, severity of stenosis, individual factors, efficacy and risk of complications. The aim of this paper is to review current evidence and guidelines on the management of carotid artery stenosis, including the comparison of medical and interventional therapy (CAS and CEA), as well as future directions.

Topics: Brain Ischemia; Cardiovascular Agents; Carotid Stenosis; Clinical Decision-Making; Endarterectomy, Carotid; Endovascular Procedures; Humans; Risk Assessment; Risk Factors; Risk Reduction Behavior; Severity of Illness Index; Stents; Stroke; Treatment Outcome

Delayed cerebral ischemia seriously affects the prognosis of patients surviving the initial aneurysmal subarachnoid hemorrhage. Application of cilostazol was reported to ameliorate vasospasm and improve outcomes in series and clinical trials. But the effectiveness and feasibility of cilostazol on aneurysmal subarachnoid hemorrhage remained controversial. We performed a systematic review to clarify this issue.. PubMed, Ovid and Cochrane library database were systematically searched up to May 2018 for eligible publications in English. Quality assessment was conducted for included studies. Meta-analysis was conducted to evaluate the overall effect on events of interest. Subgroup analyses and sensitivity analyses were used to check whether the results were robust. Publication bias was evaluated with the funnel plot.. Pooled analyses found cilostazol significantly reduced incidences of severe angiographic vasospasm (p = 0.0001), symptomatic vasospasm (p < 0.00001), new cerebral infarction (p < 0.00001) and the poor outcome (p < 0.0001). Subgroup and sensitivity analyses achieved consistent results. There was no statistical difference between cilostazol and the control group in reducing mortality (p = 0.07). But sensitivity analysis changed the result after excluding one study. Under the prescribed dosage, complication was few and non-lethal.. Cilostazol was effective and safe to reduce incidences of severe angiographic vasospasm, symptomatic vasospasm, new cerebral infarction and poor outcome in patients after aneurysmal subarachnoid hemorrhage. However, its effect on mortality and the interactive effect with nimodipine warranted further research.

Topics: Brain Ischemia; Cardiovascular Agents; Cerebral Infarction; Cilostazol; Humans; Intracranial Aneurysm; Outcome Assessment, Health Care; Subarachnoid Hemorrhage; Vasospasm, Intracranial

This article provides the first extensive documentation of the dose response features of pre- and postconditioning. Pre- and postconditioning studies with rigorous study designs, using multiple doses/concentrations along with refined dose/concentration spacing strategies, often display hormetic dose/concentration response relationships with considerable generality across biological model, inducing (i.e., conditioning) agent, challenging dose treatment, endpoint, and mechanism. Pre- and postconditioning hormesis dose/concentration-response relationships are reported for 154 diverse conditioning agents, affecting more than 550 dose/concentration responses, across a broad range of biological models and endpoints. The quantitative features of the pre- and postconditioning-induced protective responses are modest, typically being 30-60% greater than control values at maximum, findings that are consistent with a large body (>10,000) of hormetic dose/concentration responses not related to pre- and postconditioning. Regardless of the biological model, inducing agent, endpoint or mechanism, the quantitative features of hormetic dose/concentration responses are similar, suggesting that the magnitude of response is a measure of biological plasticity. This paper also provides the first documentation that hormetic effects account for preconditioning induced early (1-3h) and delayed (12-72h) windows of protection. These findings indicate that pre- and postconditioning are specific types of hormesis.

Topics: Animals; Brain; Brain Ischemia; Cardiovascular Agents; Cytoprotection; Disease Models, Animal; Heart; Hormesis; Humans; Myocardial Reperfusion Injury; Myocardium; Neuroprotective Agents; Reperfusion Injury; Time Factors; Treatment Outcome

Described in the article is a rare case concerning spontaneous recanalization of the extracranial portion of the internal carotid artery (ICA) eleven months after occlusion. Only few publications have been dedicated to recanalization of ICA chronic occlusion. Spontaneous recanalization of the ICA is more common than it is generally understood. The authors have analysed all available articles about this problem from PubMed (1957 to 2013), reviewing the mechanisms of recanalization of the ICA, methods of diagnosis and treatment. The purpose of this case report is to emphasize the importance of ICA spontaneous recanalization and consequences thereof.

Topics: Angiography; Brain Ischemia; Cardiovascular Agents; Carotid Artery, Internal; Carotid Stenosis; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Prognosis; Recovery of Function; Remission, Spontaneous; Tomography, X-Ray Computed; Ultrasonography, Doppler, Color; Vascular Patency

The official statistics of the Ministry of Health of the Russian Federation show that the past 10 years have been marked by an increase in the number of patients with chronic cerebral circulatory disorders (CCCD), accounting for at least 700 per 100,000 population. Hypertension is the most studied etiological factor of CCCD. However, its role is often perceived uniquely as the major mechanism for destabilization of the arterial vascular bed. The detailed study of the pathogenesis of impairments in the cerebral vascular bed and neurons will be able to predict the further course of the disease and to choose adequate therapy.

Topics: Brain Ischemia; Cardiovascular Agents; Cerebrovascular Circulation; Chronic Disease; Disease Management; Humans; Hypertension; Prognosis

Approximately one in four ischemic strokes is of cardioembolic origin. Non-valvular atrial fibrillation accounts for 50% of these cases, followed by myocardial infarction, intraventricular thrombus, valvular heart disease and a miscellany of causes. The incidence of embolic heart disease in the population could be about 30 cases per 100,000 inhabitants per year, and its prevalence between 5 and 10 cases per 1,000 persons aged 65 years or older. Hospital mortality is high, and 5-year survival is only one out of every five patients. The recurrence rate of this type of stroke is about 12% at 3 months, higher than that of non-cardioembolic stroke. The severity of cardioembolic strokes and the resulting disability are greater than with non-cardioembolic stroke. Age, a history of stroke or transient ischemic attack, hypertension, diabetes and heart failure play a role in stroke with atrial fibrillation as additional risk factors for future embolisms. Stroke rates can reach over 20% per year and therefore the prevention and treatment of these events are of paramount importance.

Topics: Age Distribution; Atrial Fibrillation; Brain Damage, Chronic; Brain Ischemia; Cardiovascular Agents; Comorbidity; Diabetes Mellitus; Female; Heart Valve Diseases; Humans; Hypertension; Intracranial Embolism; Male; Myocardial Infarction; Prevalence; Recurrence; Risk Factors; Sex Distribution; Survival Rate; Thrombophilia

Atrial fibrillation (AF) is the most frequent heart arrhythmia and causes a substantial proportion of ischemic strokes. AF has a marked impact on stroke severity, as well as on morbidity and mortality in these patients. The importance of AF as an etiologic factor of stroke increases in the elderly and in the last few years its detection has increased. The presence of AF leads to more severe initial neurological involvement, longer hospitalization, greater disability and a lower probability of discharge to home. In addition, AF is an independent risk factor for mortality, especially in women and the elderly. All these factors lead to a higher social and economic impact among stroke patients with AF.

Topics: Atrial Fibrillation; Brain Damage, Chronic; Brain Ischemia; Cardiovascular Agents; Cost of Illness; Female; Health Care Costs; Health Expenditures; Hospitalization; Humans; Intracranial Embolism; Male; Prevalence; Quality of Life; Risk Factors; Social Adjustment; Social Change; Socioeconomic Factors; Stroke

The purpose of this article is to describe the modern management of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (SAH). SAH causes an inflammatory reaction to blood products in the basal cisterns of the brain, which may produce cerebral ischemia and strokes through progressive narrowing of the cerebral artery lumen. This process, known as cerebral vasospasm, is the most common cause of DCI after SAH. Untreated DCI may result in strokes, which account for a significant portion of the death and long-term disability after SAH.. A number of publications, including two recent consensus statements, have clarified many best practices for defining, diagnosing, monitoring, preventing, and treating DCI. DCI is best defined as new onset of focal or global neurologic deficits or strokes not attributable to another cause. In addition to the clinical examination, radiographic studies such as transcranial Doppler ultrasonography, CT angiography, and CT perfusion may have a role in determining which patients are at high risk for developing DCI. The mainstay of prevention and treatment of DCI is maintenance of euvolemia, which can be a difficult therapeutic target to measure. Hemodynamic augmentation with induced hypertension with or without inotropic support has become the first-line treatment of DCI. The ideal method of measuring hemodynamic values and volume status in patients with DCI remains elusive. In patients who do not adequately respond to or cannot tolerate hemodynamic augmentation, endovascular therapy (intraarterial vasodilators and balloon angioplasty) is a complementary strategy. Optimal triggers for escalation and de-escalation of therapies for DCI have not been well defined.. Recent guidelines and consensus statements have clarified many aspects of prevention, monitoring, and treatment of DCI after SAH. Controversies continue regarding the optimal methods for measurement of volume status, the role of invasive neuromonitoring, and the targets for hemodynamic augmentation therapy.

Topics: Angioplasty, Balloon; Brain Ischemia; Calcium Channel Blockers; Cardiovascular Agents; Cerebral Angiography; Combined Modality Therapy; Consensus Development Conferences as Topic; Disease Management; Fluid Therapy; Hemodynamics; Humans; Hypertension; Intracranial Aneurysm; Neuroimaging; Nimodipine; Practice Guidelines as Topic; Rupture, Spontaneous; Subarachnoid Hemorrhage; Ultrasonography, Doppler, Transcranial; Vasospasm, Intracranial

Epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP450) products of arachidonic acid and EETs are endogenous lipid mediators synthesized by the vascular endothelium which perform important biological functions, including vasodilation, anti-inflammation, antimigratory, and cellular signaling regulations. However, EETs are rapidly degraded by soluble epoxide hydrolase (sEH) to the corresponding diols: dihydroxyeicosatrienoic acids (DHETs), which have little active in causing vasorelaxation. A number of studies have supported that the inhibition of sEH (sEHIs) had cardiovascular protective effects in hypertension, cardiac hypertrophy, atherosclerosis, ischemia-reperfusion injury, and ischemic stroke. Moreover, sEHIs could slow the progression of inflammation, protect end-organ damage and prevent ischemic events, also, attenuate endothelial dysfunction, suggesting that the pharmacological blockade of sEH might provide a broad and novel avenue for the treatment of many cardiovascular diseases.

Topics: Animals; Brain Ischemia; Cardiomegaly; Cardiovascular Agents; Cardiovascular Diseases; Enzyme Inhibitors; Epoxide Hydrolases; Humans; Hypertension; Polymorphism, Genetic; Reperfusion Injury; Risk; Stroke

Stroke is a major cause of death and disability worldwide. Without improvements in prevention, the burden will increase during the next 20 years because of the ageing population, especially in developing countries. Major advances have occurred in secondary prevention during the past three decades, which demonstrate the broader potential to prevent stroke. We review the main medical treatments that should be considered for most patients with transient ischaemic attack or ischaemic stroke in the acute phase and the long term, and draw attention to recent developments.

Topics: Acute Disease; Anticoagulants; Antihypertensive Agents; Atrial Fibrillation; Brain Ischemia; Cardiovascular Agents; Cholesterol, HDL; Cholesterol, LDL; Chronic Disease; Developing Countries; Dyslipidemias; Fibrinolytic Agents; Humans; Hypertension; Hypolipidemic Agents; Ischemic Attack, Transient; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Secondary Prevention; Stroke; Time Factors; Triage

We assessed the prevalence, and potential impact of, trials of pharmacological agents for acute stroke that were completed but not published in full. Failure to publish trial data is to be deprecated as it sets aside the altruism of participants' consent to be exposed to the risks of experimental interventions, potentially biases the assessment of the effects of therapies, and may lead to premature discontinuation of research into promising treatments.. We searched the Cochrane Stroke Group's Specialised Register of Trials in June 2008 for completed trials of pharmacological interventions for acute ischaemic stroke, and searched MEDLINE and EMBASE (January 2007 - March 2009) for references to recent full publications. We assessed trial completion status from trial reports, online trials registers and correspondence with experts.. We identified 940 trials. Of these, 125 (19.6%, 95% confidence interval 16.5-22.6) were completed but not published in full by the point prevalence date. They included 16,058 participants (16 trials had over 300 participants each) and tested 89 different interventions. Twenty-two trials with a total of 4,251 participants reported the number of deaths. In these trials, 636/4251 (15.0%) died.. Our data suggest that, at the point prevalence date, a substantial body of evidence that was of relevance both to clinical practice in acute stroke and future research in the field was not published in full. Over 16,000 patients had given informed consent and were exposed to the risks of therapy. Responsibility for non-publication lies with investigators, but pharmaceutical companies, research ethics committees, journals and governments can all encourage the timely publication of trial data.

Topics: Brain Ischemia; Cardiovascular Agents; Clinical Trials as Topic; Evidence-Based Medicine; Humans; Information Dissemination; Informed Consent; Publishing; Risk Assessment; Stroke; Treatment Outcome

Numerous neuroprotective agents have proven effective in animal stroke studies, but every drug has failed to achieve its primary outcome when brought forward to clinical trials. We analyzed the quality and adequacy of animal studies supporting the efficacy of NXY-059 and other neuroprotective agents that are currently being investigated in phase II/III trials.. We conducted a systematic search of all neuroprotective drugs in Phase II or III trials and collected data from animal studies of focal cerebral ischemia testing agents systemically administered within 24 hours of occlusion. The methodological rigor of each individual study was evaluated using 5 criteria derived from the STAIR guidelines. The adequacy of the preclinical "package" for each drug was then evaluated by combining the results of all studies for each drug to determine which of a further 5 STAIR criteria were met before moving forward from animal to human studies.. Our search yielded 13 agents of which 10 had published data in peer-reviewed journals. There is substantial within-drug variability in the quality of preclinical studies as well as substantial variation in the completeness of the collective preclinical literature for different drugs. There has been little or no improvement in the quality of animal studies since NXY-059, and current agents have not been subjected to a more complete preclinical evaluation.. There is significant heterogeneity in the quality of animal testing for neuroprotective agents in stroke. Drugs in the post-SAINT era have not been subjected to more thorough preclinical evaluation.

Topics: Acute Disease; Animals; Benzenesulfonates; Brain Ischemia; Cardiovascular Agents; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Disease Models, Animal; Humans; Neuroprotective Agents; Research; Research Design; Risk; Stroke

The neutral results of the SAINT II trial have again highlighted difficulties translating neuroprotective efficacy from bench to bedside. Animal studies are susceptible to study quality biases, which may lead to overstatement of efficacy. We report the impact of study quality on published estimates of the efficacy of NXY-059 in animal models of stroke.. We conducted a systematic review and stratified meta-analysis of published studies describing the efficacy of NXY-059 in experimental focal cerebral ischemia.. Overall, NXY-059 improved infarct volume by 43.3% (95% CI, 34.7 to 52.8). Only 2 of 9 publications reported randomization, concealment of treatment allocation, and blinded outcome assessment. Studies not reporting these quality items gave substantially higher estimates of efficacy than did higher-quality studies.. The reported efficacy of NXY-059 in animal models of stroke is confounded by low study quality. The failure of SAINT II highlights the need for substantial improvements in the design, conduct, and reporting of animal studies; journals can play an important role in this by adopting standards for animal studies similar to those agreed over 10 years ago for clinical trials.

Topics: Animals; Benzenesulfonates; Bias; Brain Ischemia; Cardiovascular Agents; Clinical Trials as Topic; Research Design

The continued failure in approving new drugs for treatment of acute stroke has been recently set back by the failure of the NXY-059 (Stroke-Acute Ischemic NXY Treatment (SAINT) II) trial. The disappointment was heightened by the latter study being viewed as a most promising compound for stroke drug development program based on the preclinical data. Since the SAINT I/II development program included many of the STAIR (Stroke Therapy Academic Industry Round table) guidelines, yet have still failed to achieve the expected efficacy, there is a clear need to continue and analyze the path forward for stroke drug discovery. To this end, this review calls for a consortium approach including academia, government (FDA/NIH), and pharmaceutical industry partnerships to define this path. It is also imperative that more attention is given to the evolving discipline of Translational Medicine. A key issue in this respect is the need to devote more attention to the characteristics of the drug candidate nature-target interaction, and its relationship to pharmacodynamic treatment end points. It is equally important that efforts are spent to prove that phenotypic outcomes are linked to the purported mechanism of action of the compound. Development of technologies that allows a better assessment of these parameters, especially in in vivo models are paramount. Finally, rational patient selection and new outcome scales tailored in an adaptive design model must be evaluated.

Topics: Benzenesulfonates; Brain Ischemia; Cardiovascular Agents; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Approval; Drug Design; Drug Industry; Endpoint Determination; Guidelines as Topic; Humans; Models, Cardiovascular; National Institutes of Health (U.S.); Patient Selection; Stroke; Treatment Outcome; United States; United States Food and Drug Administration

Acute ischemic stroke (AIS) is a significant cause of death and disability in the United States. It has been 10 years since tissue plasminogen activator became the first medication approved by the US Food and Drug Administration for treatment for AIS. However, this treatment simply reopens arteries. The identification of deleterious cellular reactions that occur secondary to cerebral ischemia has led investigators to search for neuroprotection strategies to complement reperfusion. More than 100 human trials, including a handful of phase III trials, had failed to produce an efficacious neuroprotective agent. In 2006, the first positive trial of neuroprotection was published: the SAINT I (Stroke-Acute Ischemic NXY Treatment) study. In February 2008, the SAINT II study was published, indicating that NXY-059 was not effective for AIS treatment.

Topics: Acute Disease; Benzenesulfonates; Brain Ischemia; Cardiovascular Agents; Clinical Trials as Topic; GABA Agonists; Humans; Hypothermia; N-Methylaspartate; Narcotic Antagonists; Neuroprotective Agents; Stroke; Tissue Plasminogen Activator

Cardiovascular diseases, the clinical paradigm of atherosclerosis, are the primary cause of mortality in developed countries. The origin of the atheromatous lesion is multifactorial, as it is the therapeutic approach to its prevention and clinical complications. The initial symptoms of ischemia in a vascular bed are usually evident when the atherosclerotic process is very advanced, being indicative of a diffuse disease and of an elevated future risk for ischemic events in other vascular territories. We perform this review in this clinical scenario, highlighting the preventive and therapeutic aspects of demonstrated clinical efficacy, with no detail of those treatments with benefit insufficiently proven.

Topics: Angina Pectoris; Anticoagulants; Atherosclerosis; Brain Ischemia; Cardiovascular Agents; Combined Modality Therapy; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Myocardial Ischemia; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Risk Factors

Topics: Acute Disease; Animals; Benzenesulfonates; Brain Ischemia; Cardiovascular Agents; Humans; Nitrogen Oxides; Stroke

A variety of primary end points have been used in acute stroke trials. We focus on the modified Rankin Scale, a reliable and valid ordinal outcome measure that assesses disability on a 7-point scale.. We provide an abbreviated discussion of analytical methods for ordinal scales, and related effect size measures; we illustrate these methods and their interpretation with outcome data from the SAINT I study of NXY-059 in acute ischemic stroke.. The nonparametric Mann-Whitney statistic provides a straightforward method for analysis of the modified Rankin Scale, and incorporates associated measures of effect size. These measures are directly related to the concepts of Number Needed to Treat and Number Needed to Harm.. Our re-examination of the outcome data from the SAINT I study provides little evidence for the purported efficacy of NXY-059. More broadly, analysis and interpretation of ordinal outcome scales based on ascribed numerical values to the steps of the scale should be done cautiously. Statistical treatment of multiple primary outcome measures in acute stroke clinical trials should be established before analysis. Lastly, conflating statistical and clinical significance should be avoided.

Topics: Acute Disease; Benzenesulfonates; Biomarkers; Brain Damage, Chronic; Brain Ischemia; Cardiovascular Agents; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Disability Evaluation; Double-Blind Method; Free Radical Scavengers; Humans; Neuroprotective Agents; Neuropsychological Tests; Nitrogen Oxides; Randomized Controlled Trials as Topic; Sample Size; Severity of Illness Index; Statistics, Nonparametric; Stroke; Treatment Failure; Treatment Outcome

We conducted a Medline search for controlled studies evaluating currently available drugs for pharmacological neuroprotection. They had to be administered prior to transient global cerebral ischaemia without further non-pharmacological measures. We deliberately excluded focal ischaemia since its pathophysiology is substantially different from global ischaemia. A total of 45 articles conducted exclusively in laboratory animals met these criteria. The following classes of agents were evaluated: anaesthetics, GABAergic drugs, calcium-antagonists, anticonvulsives, sodium-channel blockers, potassium-channel activators, NMDA-receptor antagonists, hormones, vasodilators, dopamine- and alpha2-agonists, magnesium, xanthine oxidase- and cyclooxygenase inhibitors, a nootropic, a protease inhibitor, and immunosuppressants. Some of them were applied chronically and others administered via clinically impracticable routes. The available literature favours isoflurane, phenytoin, lamotrigine, magnesium, and potentially, nimodipine, and flunarizine. If factors like costs, toxicity, side effects, route and mode of application are considered, isoflurane and MgSO4 that have also been safely applied to patients with compromised left ventricular pump function are advantageous but their true role in human neuroprotection remains unclear.

Topics: Animals; Brain Ischemia; Cardiovascular Agents; Central Nervous System Agents; Disease Models, Animal; Dopamine; Enzyme Inhibitors; Estradiol; Heart Arrest; Humans; Immunosuppressive Agents; Magnesium; Neuroprotective Agents; Neurotransmitter Agents; Potassium Channels; Progesterone; Receptors, N-Methyl-D-Aspartate

Stroke continues to have a devastating impact on public health. Recent epidemiological studies suggest that stroke is becoming more common, perhaps due to the ageing of the population and increased survival of patients with cardiac disease. There are specific and well-defined risk factors in patients with stroke, the most important being hypertension. Treatment options to reverse the effect of acute ischaemic stroke are limited. The only approved therapy is intravenous tissue plasminogen activator (tPA). The disadvantage of tPA treatment is a rate of symptomatic haemorrhage of about 6%. Newer stroke prevention options are currently being investigated including statins, oestrogen, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). The challenge for physicians is to select the most effective intervention, and this depends on our knowledge of the underlying stroke mechanism and the patient's risk factors.

Topics: Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Brain Ischemia; Cardiovascular Agents; Female; Humans; Hypertension; Male; Middle Aged; Risk Factors; Stroke; United States

Topics: Acute Disease; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Antibodies; Brain Ischemia; Calcium Channel Blockers; Cardiovascular Agents; Cell Adhesion Molecules; Clinical Trials as Topic; Cytidine Diphosphate Choline; Cytokines; Drug Therapy, Combination; Fibrinolytic Agents; Free Radical Scavengers; gamma-Aminobutyric Acid; Growth Substances; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; N-Methylaspartate; Neuroprotective Agents; Nootropic Agents; Piperidines; Stroke; Thiazoles; Thrombolytic Therapy

Numerous studies have consistently shown that agonist stimulation of adenosine A1 receptors results in a significant reduction of morbidity and mortality associated with global and focal brain ischemia in animals. Based on these observations, several authors have suggested utilization of adenosine A1 receptors as targets for the development of clinically viable drugs against ischemic brain disorders. Recent advent of adenosine A1 receptor agonists characterized by lowered cardiovascular effects added additional strength to this argument. On the other hand, although cardioprotective, adenosine A3 receptor agonists proved severely cerebrodestructive when administered prior to global ischemia in gerbils. Moreover, stimulation of adenosine A3 receptors appears to reduce the efficacy of some of the neuroprotective actions mediated by adenosine A receptors. The review discusses the possible role of adenosine receptor subtypes (A1, A2, and A3) in the context of their involvement in the pathology of cerebral ischemia, and analyzes putative strategies for the development of clinically useful strategies based on adenosine and its receptors. It also stresses the need for further experimental studies before definitive conclusions on the usefulness of the adenosine concept in the treatment of brain ischemia can be made.

Topics: Adenosine; Animals; Brain Ischemia; Cardiovascular Agents; Humans; Purinergic P1 Receptor Agonists

To review the published data concerning the vasomotor responses of arterioles on the surface of the mouse brain. This information is essential to the planning of studies using genetically manipulated mice to investigate the control of cerebral vascular resistance.. Cerebral vasomotor responses of mice have been reported using a wide variety of vasoactive agents. The responses are usually like those of other laboratory animals. Some agents are capable of eliciting opposing dilating and constricting responses. The initial tone of the arteriole is one of several factors that can determine the direction of the response elicited by such agents. Endothelium-dependent dilators and constrictors have been described. There are a variety of endothelium-derived relaxing factors (EDRFs). Only one of these is synthesized by nitric oxide synthase (NOS). Antisense data suggests that both the endothelial and the neuronal isoforms of NOS may exist in the endothelial cells of these vessels. Several diseases can be modeled in mice and cerebrovascular responses studied. Studies of genetically modified mice suggest that the endothelial form of NOS contributes to microvascular events, which limit ischemic damage to brain parenchyma. However, during and following ischemia there may be loss of this NOS or inability to mobilize a storage form of the EDRF, which it produces.. Data available from studies of mice provide a good basis for planning further studies, examining cerebrovascular control mechanisms in health and disease, by workers now using genetically modified mice. The latter represent a powerful and increasingly popular tool for this purpose.

Topics: Animals; Arterioles; Brain; Brain Ischemia; Cardiovascular Agents; Cerebrovascular Circulation; Disease Models, Animal; Mice; Mice, Mutant Strains; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Species Specificity; Vascular Resistance; Vasoconstriction; Vasodilation

A number of therapeutic options are available to clinicians caring for patients with ischemic cerebrovascular diseases. The efficacy of some strategies that aim at mitigating the effects of cerebral infarction are presented. The optimal role of carotid surgery, platelet-antiaggregant drugs and anticoagulation in the prevention of stroke are analysed.

Topics: Brain Ischemia; Cardiovascular Agents; Carotid Artery Diseases; Cerebrovascular Disorders; Combined Modality Therapy; Drug Therapy, Combination; Endarterectomy; Humans

Atherosclerosis is one of the main mechanisms of stroke and cardiovascular diseases and is associated with increased risk of recurrent stroke and cardiovascular events. Intima-medial thickness (IMT) is a well-known surrogate marker of atherosclerosis and has been used to predict stroke and cardiovascular events. However, the clinical significance of IMT and IMT change in stroke has not been investigated in well-designed studies. The PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage-Intima-Media Thickness (PICASSO-IMT) sub-study is designed to investigate the effects of cilostazol, probucol, or both on IMT in patients with stroke.. PICASSO-IMT is a prospective sub-study of the PICASSO study designed to measure IMT and plaque score at 1, 13, 25, 37, and 49 months after randomization.. The primary outcome is the change in mean carotid IMT, which is defined as the mean of the far-wall IMTs of the right and left common carotid arteries, between baseline and 13 months after randomization.. PICASSO-IMT will provide the largest IMT data set in a stroke population and will provide valuable information about the clinical significance of IMT in patients with ischemic stroke.

Topics: Brain Ischemia; Cardiovascular Agents; Carotid Artery Diseases; Carotid Artery, Common; Carotid Intima-Media Thickness; Cerebral Hemorrhage; Cilostazol; Clinical Protocols; Double-Blind Method; Humans; Predictive Value of Tests; Probucol; Prospective Studies; Republic of Korea; Research Design; Risk Factors; Stroke; Tetrazoles; Time Factors; Treatment Outcome

Danhong injection (DHI) has been widely prescribed to patients with acute ischemic stroke (AIS). However, due to methodological deficiencies, previous research has not yet provided rigorous evidence to support the use of DHI in the treatment of AIS. Therefore, we designed this multicenter, randomized, controlled, and double-blind trial to evaluate the efficacy and safety of DHI for AIS.. It is a randomized, multicenter, double-blind, placebo-controlled, adaptive clinical trial. A total of 864 eligible patients will be randomized into either the DHI or placebo group in a 2:1 ratio. All patients will be given the standard medical care as recommended by guidelines. Participants will undergo a 2-week treatment regimen and 76-day follow-up period. The primary outcome is the proportion of patients with a favorable outcome, defined as a score of 0-1 on the modified Rankin scale at day 90. Secondary outcomes include a change in the total score of the Chinese medicine symptom scales of "Xueyu Zheng" (blood stasis syndrome), the proportion of patients with a Barthel Index score of ≥90, the proportion of patients with an improvement in NIHSS score of ≥4 or NIHSS score of 0-1, quality of life measured by the EQ-5D scale, etc. Safety outcomes such as global disability (mRS ≥3) at day 90 will also be assessed. The changes in mRNA and microRNA profiles in 96 patients selected from certain centers will also be assessed. As this is an adaptive design, two interim analyses are prospectively planned, which will be carried out after one-third and two-thirds of patients have completed the trial, respectively. Based on the results of the interim analyses, the Data Monitoring Committee (DMC) will decide how to modify the study.. This trial will provide high-quality evidence for DHI in treatment of AIS.. Clinical Trials.gov NCT01677208 (Date of registration 22 December 2012).

Topics: Adolescent; Adult; Aged; Brain Ischemia; Cardiovascular Agents; China; Clinical Protocols; Disability Evaluation; Double-Blind Method; Drugs, Chinese Herbal; Female; Gene Expression Profiling; Genetic Markers; Humans; Injections; Male; MicroRNAs; Middle Aged; Quality of Life; Research Design; RNA, Messenger; Stroke; Surveys and Questionnaires; Time Factors; Treatment Outcome; Young Adult

The aim of this study was to determine the impact of mean platelet volume (MPV) on the strategy for treatment of atrial fibrillation (AF) with respect to stroke prevention. MPV was analyzed in 265 patients with AF who were undergoing treatment using rhythm or rate control. The primary endpoint was ischemic stroke or a transient ischemic attack (TIA) event. Kaplan-Meier analysis revealed a significantly higher stroke rate in the rate control group compared to the rhythm control group. A significantly higher stroke rate was observed in the higher tertile MPV group (≥7.9 fL) compared to the lower tertile MPV group (<7.3 fL). When the MPV cut-off level was set to 7.85 fL using the receiver operating characteristic curve, the sensitivity was 80.0% and the specificity was 70.4% for differentiating between the group with stroke and the group without stroke. In the Cox proportional hazard analysis, after adjusting for sex, treatment strategy for AF, high MPV level, antithrombotic treatment, and high CHADS2 score, higher MPV, rate control strategy for treatment of AF, and high CHADS2 score were found to be independent predictors of stroke risk. In addition, patients with AF who were treated using rate control had high stroke risk with an MPV over 7.85 fL and high CHADS2 score. The results of this study demonstrate that the MPV and the rate control strategy for treatment of AF were predictive markers for stroke; its predictive power for stroke was independent of female sex and high CHADS2 score in patients with AF.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Brain Ischemia; Cardiovascular Agents; Female; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Male; Mean Platelet Volume; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; ROC Curve; Sensitivity and Specificity; Stroke; Treatment Outcome

Mildronate, an inhibitor of carnitine-dependent metabolism, is considered to be an anti-ischemic drug. This study is designed to evaluate the efficacy and safety of mildronate injection in treating acute ischemic stroke.. We performed a randomized, double-blind, multicenter clinical study of mildronate injection for treating acute cerebral infarction. 113 patients in the experimental group received mildronate injection, and 114 patients in the active-control group received cinepazide injection. In addition, both groups were given aspirin as a basic treatment. Modified Rankin Scale (mRS) score was performed at 2 weeks and 3 months after treatment. National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) score were performed at 2 weeks after treatment, and then vital signs and adverse events were evaluated.. A total of 227 patients were randomized to treatment (n = 113, mildronate; n = 114, active-control). After 3 months, there was no significant difference for the primary endpoint between groups categorized in terms of mRS scores of 0-1 and 0-2 (p = 0.52 and p = 0.07, respectively). There were also no significant differences for the secondary endpoint between groups categorized in terms of NIHSS scores of >5 and >8 (p = 0.98 and p = 0.97, respectively) or BI scores of >75 and >95 (p = 0.49 and p = 0.47, respectively) at 15 days. The incidence of serious adverse events was similar between the two groups.. Mildronate injection is as effective and safe as cinepazide injection in treating acute cerebral infarction.

Topics: Aged; Brain Ischemia; Cardiovascular Agents; Double-Blind Method; Female; Humans; Male; Methylhydrazines; Middle Aged; Stroke; Treatment Outcome

Levetiracetam (LEV) monotherapy was investigated in 35 patients (pts) (16M/19F, 71.9+/-7.3 years of age) with late-onset post-stroke seizures (i.e. seizures occurring at least 2 weeks after an ischemic stroke) in a prospective open-label study. Overall, 27 pts (77.1%) achieved a condition of seizure freedom (defined as 1 year without seizures): 19 (54.3%) at a daily LEV dose of 1000mg, 7 (20.0%) at 1500mg, 1 (2.8%) at 2000mg. Four pts (11.4%) discontinued the drug because of intolerable side effects (drowsiness associated to gait disturbance in 1 pt, and aggressive behaviour in the remaining 3 pts); 3 pts were unresponsive at a dose of 3000mg, and 1 pt was lost at follow-up. These observations suggest that LEV exhibits safety and efficacy profiles which make it an optimal candidate as a first-choice drug against post-stroke seizures.

Topics: Aged; Aged, 80 and over; Aggression; Anticonvulsants; Brain Ischemia; Cardiovascular Agents; Drug Interactions; Epilepsy; Female; Fibrinolytic Agents; Gait Ataxia; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Sleep Stages

The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke. We sought confirmation of efficacy in a second, larger trial.. We enrolled 3306 patients with acute ischemic stroke in a randomized, double-blind trial to receive a 72-hour infusion of intravenous NXY-059 or placebo within 6 hours after the onset of stroke symptoms. Our primary end point was the distribution of disability scores on the modified Rankin scale at 90 days. We examined scores on neurologic and activities-of-daily-living scales as secondary end points. We also tested the hypothesis that NXY-059 would reduce alteplase-related intracranial hemorrhages.. The efficacy analysis was based on 3195 patients. Prognostic factors were well balanced between the treatment groups. Mortality was equal in the two groups, and adverse-event rates were similar. The distribution of scores on the modified Rankin scale did not differ between the group treated with NXY-059 (1588 patients) and the placebo group (1607 patients; P=0.33 by the Cochran-Mantel-Haenszel test; odds ratio for limiting disability, 0.94; 95% confidence interval [CI], 0.83 to 1.06). Analysis of categorized scores on the modified Rankin scale confirmed the lack of benefit: the odds ratio for trichotomization into modified Rankin scale scores of 0 to 1 versus 2 to 3 versus 4 to 6 was 0.92 (95% CI, 0.80 to 1.06). There was no evidence of efficacy for any of the secondary end points. Among patients treated with alteplase, there was no difference between the NXY-059 group and the placebo group in the frequency of symptomatic or asymptomatic hemorrhage.. NXY-059 is ineffective for the treatment of acute ischemic stroke within 6 hours after the onset of symptoms. (ClinicalTrials.gov number, NCT00061022 [ClinicalTrials.gov].)

Topics: Acute Disease; Aged; Benzenesulfonates; Brain Ischemia; Cardiovascular Agents; Double-Blind Method; Female; Humans; Infusions, Intravenous; Male; Odds Ratio; Stroke; Time Factors; Treatment Failure

We aimed to assess the safety and efficacy of lubeluzole in patients with a clinical diagnosis of acute (< 6 hours) ischemic stroke in the carotid artery territory.. A randomized, double-blind, placebo-controlled multicenter trial was conducted in 232 patients. Because treatment was administered within 6 hours and a CT scan was not mandatory before the start of treatment, 39 patients with either an intracerebral hemorrhage or ischemic stroke in the vertebrobasilar circulation were excluded from the primary efficacy analysis as prespecified in the protocol. Of the 193 patients with acute ischemic stroke in the carotid artery territory (target population), 61 received placebo, 66 lubeluzole 7.5 mg over 1 hour followed by 10 mg/d for 5 days, and 66 lubeluzole 15 mg over 1 hour followed by 20 mg/d for 5 days.. The trial, initially aimed at a patient inclusion of 270, was terminated prematurely according to the advice of the Safety Committee because of an imbalance in mortality between the treatment groups. Mortality rates at the final follow-up of 28 days for placebo, lubeluzole 10 mg/d, and lubeluzole 20 mg/d were, respectively, 18%, 6%, and 35% in the target population, results that were confirmed in the intent-to-treat population. Multivariate logistic regression analysis showed that the lower mortality in the lubeluzole 10 mg/d group was significantly in favor of the 10 mg/d treatment (P = .019). The higher mortality rate in the 20 mg/d group could be explained, at least in part, by an imbalance at randomization that led to a higher number of patients in that group with severe ischemic stroke. A total of 26 of 66 patients (39%) who received lubeluzole 10 mg/d had a score on the Barthel Index of > 70 at day 28, indicating no or mild disability, compared with 21 of 61 (34%) in the placebo group and 19 of 66 (29%) in the lubeluzole 20 mg/d group (P = NS).. In patients with acute ischemic stroke, the dosage regimen of 7.5 mg over 1 hour followed by 10 mg/d of intravenous lubeluzole is safe and statistically significantly reduced mortality. Further clinical trials in a larger number of patients are ongoing to confirm efficacy.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Brain Ischemia; Cardiovascular Agents; Carotid Artery Diseases; Cerebrovascular Disorders; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Injections, Intravenous; Logistic Models; Male; Middle Aged; Multivariate Analysis; Piperidines; Placebos; Safety; Thiazoles

Stroke is one of the leading causes of death and disability globally, while intravenous thrombolysis with recombinant tissue plasminogen activator remains the only Food and Drug Administration (FDA)-approved therapy for ischemic stroke. The attempts to develop new treatments for acute ischemic stroke meet costly and spectacularly disappointing results, which requires both long time and high costs, whereas repurposing of safe existing drugs to new indications provides a cost-effective and not time-consuming alternative. Vascular protection is a promising strategy for improving stroke outcome, as vascular function is critical to both cardiovascular diseases (CVD) and ischemic cerebrovascular disease (ICD). Vascular function related biological processes and pathways maybe the critical associations between CVD and ICD. In this study, a multi-database, in silico target identification, gene function enrichment, and network pharmacology analysis integration approach was proposed and applied to investigate the FDA-approved CVD drugs repurposing for ICD. A list of 119 candidate drugs can be obtained for further investigation of their potential in ICD treatment. As a pleiotropic drug with multi-target, carvedilol was set an example to investigate its promising potential for ICD therapy. Our results indicated that the mode of action of carvedilol for ICD treatment may tightly associated with vascular function regulation and the mechanism is multi-target and multi-signaling pathway related. The disease-disease association network-assisted prediction needs further investigations. In summary, the proposed methods herein may provide a promising alternative to inferring novel disease indications for known drugs.

Topics: Brain Ischemia; Cardiovascular Agents; Cerebrovascular Disorders; Databases, Factual; Drug Repositioning; Gene Regulatory Networks; Humans

Ginkgolide terpenoid lactones, including ginkgolides and bilobalide, are two crucial bioactive constituents of extract of Ginkgo biloba (EGb) which was used in the treatment of cardiovascular and cerebrovascular diseases. The aims of this study were to investigate the antioxidant effects and mechanism of ginkgolides (ginkgolide A (GA), ginkgolide B (GB), ginkgolide K (GK)) and bilobalide (BB) against oxidative stress induced by transient focal cerebral ischemia. In vitro, SH-SY5Y cells were exposed to oxygen-glucose deprivation (OGD) for 4 h followed by reoxygenation with ginkgolides and BB treatments for 6 h, and then cell viability, superoxide dismutase (SOD), and ROS were respectively detected using kit. Western blot was used to confirm the protein levels of hemeoxygenase-1 (HO-1), quinone oxidoreductase l (Nqo1), Akt, phosphorylated Akt (p-Akt), nuclear factor-E2-related factor2 (Nrf2), and phosphorylated Nrf2 (p-Nrf2). GB combined with different concentrations of LY294002 (PI3K inhibitor) were administrated to SH-SY5Y cells for 1 h after OGD, and then p-Akt and p-Nrf2 levels were detected by western blot. In vivo, 2 h of middle cerebral artery occlusion (MCAO) model was established, followed with reperfusion and GB treatments for 24 and 72 h. The infarct volume ratios were confirmed by TTC staining. The protein levels of HO-1, Nqo1, SOD1, Akt, p-Akt, Nrf2, and p-Nrf2 were detected using western blot and immunohistochemistry (IHC). Experimental data in vitro confirm that GA, GB, GK, and BB resulted in significant decrease of ROS and increase of SOD activities and protein levels of HO-1 and Nqo1; however, GB group had a significant advantage in comparison with the GA and GK groups. Moreover, after ginkgolides and BB treatments, p-Akt and p-Nrf2 were significantly upregulated, which could be inhibited by LY294002 in a dose-dependent manner, meanwhile, GB exhibited more effective than GA and GK. In vivo, TTC staining indicated that the infarct volume ratios in MCAO rats were dramatically decreased by GB in a dose-dependent manner. Furthermore, GB significantly upregulated the protein levels of HO-1, Nqo1, SOD, p-Akt, p-Nrf2, and Nrf2. In conclusion, GA, GB, GK, and BB significantly inhibited oxidative stress damage caused by cerebral ischemia reperfusion. Compared with GA, GK, and BB, GB exerts the strongest antioxidant stress effects against ischemic stroke. Moreover, ginkgolides and BB upregulated the levels of antioxidant proteins through mediating th

Topics: Animals; Antioxidants; Brain Ischemia; Cardiovascular Agents; Cell Line, Tumor; Ginkgo biloba; Ginkgolides; Heme Oxygenase-1; Humans; Infarction, Middle Cerebral Artery; Male; NAD(P)H Dehydrogenase (Quinone); Neuroprotective Agents; NF-E2-Related Factor 2; Oxidative Stress; Plant Extracts; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley

Carotid artery web is considered an exceptional cause of recurrent ischemic strokes in the affected arterial territory. The underlying pathology proposed for this entity is an atypical fibromuscular dysplasia. We present the case of a 43-year-old woman with no cardiovascular risk factors who had experienced 2 cryptogenic ischemic strokes in the same arterial territory within an 11-month period. Although all diagnostic tests initially yielded normal results, detailed analysis of the computed tomography angiography images revealed a carotid web; catheter angiography subsequently confirmed the diagnosis. Carotid surgery was performed, since which time the patient has remained completely asymptomatic. The histological finding of intimal hyperplasia is consistent with previously reported cases of carotid artery web. Carotid artery web is an infrequent cause of stroke, and this diagnosis requires a high level of suspicion plus a detailed analysis of vascular imaging studies.

Topics: Adult; Aspirin; Atorvastatin; Biopsy; Brain Ischemia; Cardiovascular Agents; Carotid Artery Diseases; Carotid Artery, Internal; Computed Tomography Angiography; Female; Fibromuscular Dysplasia; Humans; Hyperplasia; Neointima; Recurrence; Risk Factors; Stroke

Rationale Despite several large clinical trials assessing blood pressure lowering in acute stroke, equipoise remains particularly for ischemic stroke. The "Blood pressure in Acute Stroke Collaboration" commenced in the mid-1990s focussing on systematic reviews and meta-analysis of blood pressure lowering in acute stroke. From the start, Blood pressure in Acute Stroke Collaboration planned to assess safety and efficacy of blood pressure lowering in acute stroke using individual patient data. Aims To determine the optimal management of blood pressure in patients with acute stroke, including both intracerebral hemorrhage and ischemic stroke. Secondary aims are to assess which clinical and therapeutic factors may alter the optimal management of high blood pressure in patients with acute stroke and to assess the effect of vasoactive treatments on hemodynamic variables. Methods and design Individual patient data from randomized controlled trials of blood pressure management in participants with ischemic stroke and/or intracerebral hemorrhage enrolled during the ultra-acute (pre-hospital), hyper-acute (<6 h), acute (<48 h), and sub-acute (<168 h) phases of stroke. Study outcomes The primary effect variable will be functional outcome defined by the ordinal distribution of the modified Rankin Scale; analyses will also be carried out in pre-specified subgroups to assess the modifying effects of stroke-related and pre-stroke patient characteristics. Key secondary variables will include clinical, hemodynamic and neuroradiological variables; safety variables will comprise death and serious adverse events. Discussion Study questions will be addressed in stages, according to the protocol, before integrating these into a final overreaching analysis. We invite eligible trials to join the collaboration.

Topics: Blood Pressure; Brain Ischemia; Cardiovascular Agents; Cerebral Hemorrhage; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Stroke; Systematic Reviews as Topic

It is unclear what factors providers take into account to determine the target blood pressure (BP) after mechanical thrombectomy (MT) in patients who had acute ischemic stroke. We aimed to understand practice patterns of post-MT BP management across institutions in the United States.. We surveyed StrokeNet institutions providing MT and post-MT care with an online questionnaire, designed to understand institutional post-MT BP management practices.. Of 131 potential institutions, 58 completed the survey. The majority of institutions target systolic BP (SBP, n = 53, 91%) during the first 24 hours post-MT (n = 32, 55%) using nicardipine as a first-line agent (n = 43, 74%). At most institutions, BP management is determined by a team of physicians in a collaborative fashion (n = 30, 52%) and individualized on a case-by-case basis (n = 39, 67%) after taking the reperfusion status into account (n = 42, 72%). In patients with successful reperfusion, 36% (n = 21) of the institutions target SBP in the range of 120-139 mm Hg, 21% (n = 12) target 140-159 mm Hg, and 28% (n = 16) would accept any value less than or equal to 180 mm Hg. In patients with unsuccessful reperfusion, 43% (n = 25) would accept any SBP value less than or equal to 180 mm Hg and 10% (n = 6) would target SBP less than or equal to 220 mm Hg.. We found that majority of the institutions do not have a standardized protocol for post-MT BP management. There was interinstitutional heterogeneity in the preferred target of SBP post-MT and most institutions target values of SBP lower than 180 mm Hg in post-MT patients. Prospective data and randomized control trial are needed to identify the optimal target BP.

Topics: Blood Pressure; Brain Ischemia; Cardiovascular Agents; Critical Care; Disease Management; Humans; Mechanical Thrombolysis; Nicardipine; Physicians; Stroke; Surveys and Questionnaires

Long-term progression of peripheral arterial disease (PAD) as initial manifestation of atherosclerotic arterial disease is not well described. Cardiovascular (CV) risk was examined in different PAD populations diagnosed in a hospital setting in Sweden.. Data for this retrospective cohort study were retrieved by linking data on morbidity, medication use, and mortality from Swedish national registries. Primary CV outcome was a composite of myocardial infarction, ischemic stroke (IS), and CV death. Kaplan-Meier analysis and Cox proportional hazards modeling was used for describing risk and relative risk.. Of 66,189 patients with an incident PAD diagnosis (2006-2013), 40,136 had primary PAD, 16,786 had PAD + coronary heart disease (CHD), 5803 had PAD + IS, and 3464 had PAD + IS + CHD. One-year cumulative incidence rates of major CV events for the groups were 12%, 21%, 29%, and 34%, respectively. Corresponding numbers for 1-year all-cause death were 16%, 22%, 33%, and 35%. Compared with the primary PAD population, the relative risk increase for CV events was highest in patients with PAD + IS + CHD (hazard ratio [HR], 2.01), followed by PAD + IS (HR, 1.87) and PAD + CHD (HR, 1.42). Despite being younger, the primary PAD population was less intensively treated with secondary preventive drug therapy.. PAD as initial manifestation of atherosclerotic disease diagnosed in a hospital-based setting conferred a high risk: one in eight patients experienced a major CV event and one in six patients died within 1 year. Despite younger age and substantial risk of future major CV events, patients with primary PAD received less intensive secondary preventive drug therapy.

Topics: Age Factors; Aged; Aged, 80 and over; Ambulatory Care; Brain Ischemia; Cardiovascular Agents; Cause of Death; Comorbidity; Disease Progression; Female; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Prevalence; Prognosis; Proportional Hazards Models; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Secondary Prevention; Stroke; Sweden; Time Factors

Individuals who present to the emergency departments of safety-net systems often have poorly controlled risk factors due to lack of primary care. Little is known about potential differences in presenting characteristics, discharge medications, and discharge destinations of patients with acute ischemic stroke (AIS) who present to safety-net settings versus university medical centers (UMCs).. Demographic characteristics, medical history, premorbid medication use, stroke severity, discharge medications, and discharge destination were assessed among consecutive admissions for AIS over a 2-year period at a UMC (n = 385) versus 2 university-affiliated safety-net hospitals (SNHs) (n = 346) in Los Angeles County.. Compared with patients presenting to the UMC, individuals admitted to the SNHs were younger, more frequently male, nonwhite, current smokers, hypertensive, and diabetic; they were less likely to take antithrombotics and statins before admission, and had worse serum lipid and glycemic markers (all P < .05). Patients admitted to the UMC trended toward more cardioembolic strokes and had higher stroke severity scores (P < .0001). At discharge, patients admitted to the SNHs were more likely to receive antihypertensive medications than do patients admitted to the UMC (P < .001), but there were no differences in prescription of antiplatelet medications or statins.. Individuals with AIS admitted to SNHs in Los Angeles County are younger and have poorer vascular risk factor control than their counterparts at a UMC. Discharge treatment does not vary considerably between systems. Early and more vigorous efforts at primary vascular risk reduction among patients seen at SNHs may be warranted to reduce disparities.

Topics: Academic Medical Centers; Age Factors; Aged; Aged, 80 and over; Brain Ischemia; Cardiovascular Agents; Comorbidity; Drug Prescriptions; Emergency Medical Services; Female; Health Status Disparities; Healthcare Disparities; Humans; Life Style; Los Angeles; Male; Middle Aged; Patient Admission; Patient Discharge; Risk Factors; Safety-net Providers; Stroke; Time Factors

Aspirin is known to reduce mortality and recurrent vascular events. However, there are no reports about the dose-response of loading aspirin in treating acute ischemic stroke. The objective of this study was to compare the effectiveness of different loading doses of aspirin in acute ischemic stroke presenting within 48 hours of symptom onset.. This was a retrospective, hospital-based cohort study. Patients were classified as high dose (160-325 mg) or low dose (<160 mg) based on the initial loading dose of aspirin at the emergency department. The primary outcome measure was a favorable modified Rankin Scale (mRS) score of 1 or lower on discharge. Secondary outcomes included in-hospital mortality, stroke progression during admission, and bleeding events. A propensity score with 1:3 matching was used to balance baseline characteristics, and stepwise multiple logistic regression was performed for variable adjustment.. From a total of 7738 available patients, 3802 patients were included. Among them, 750 patients were in the high-dose group. Multiple logistic regression after matching revealed that the high-dose group was significantly associated with a favorable clinical outcome on discharge (odds ratio: 1.49, 95% confidence interval: 1.17-1.89, P <.01), but not mortality or stroke progression. The high-dose group also experienced more minor bleeding events.. A higher loading dose of aspirin (160-325 mg) can be beneficial in treating acute ischemic stroke, although there is an increased risk of minor bleeding.

Topics: Aged; Aged, 80 and over; Aspirin; Brain Ischemia; Cardiovascular Agents; Disability Evaluation; Disease Progression; Female; Hemorrhage; Hospital Mortality; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Predictive Value of Tests; Propensity Score; Registries; Remission Induction; Retrospective Studies; Risk Factors; Stroke; Time Factors; Treatment Outcome

Aspirin is known to reduce stroke risk; however, its role in reducing severity of ischemic syndrome is not clear. We sought to investigate the relationship between antecedent aspirin use and stroke severity in patients presenting with acute ischemic stroke (AIS).. We retrospectively analyzed a prospectively collected database of consecutive AIS patients presenting to our center. Clinical characteristics (including antecedent aspirin use), imaging findings, and laboratory data were assessed in association with presenting stroke severity, as measured by the National Institutes of Health Stroke Scale (NIHSS). Logistic regression models were used to determine univariate and multivariate predictors of baseline NIHSS.. Of the 610 AIS patients with admission brain magnetic resonance imaging available for volumetric analysis of acute infarct size, 241 (39.5%) used aspirin prior to stroke onset. Antecedent aspirin use (P = .0005), history of atrial fibrillation (P < .0001), acute infarct volume (P < .0001), initial systolic blood pressure (P = .041), admission glucose level (P = .0027), and stroke subtype (P < .0001) were associated with presenting stroke severity in univariate analysis. Antecedent aspirin use (P < .0001), history of atrial fibrillation (P < .0002), acute infarct volume (P < .0001), systolic blood pressure (P = .038), and glucose level (P = .0095) remained independent predictors of NIHSS in multivariable analysis.. Antecedent aspirin use was independently associated with milder presenting stroke severity, even after accounting for acute infarct volume. While the underlying biology of this apparent protective relationship requires further study, patients at high risk of stroke may benefit from routine aspirin use.

Topics: Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Biomarkers; Blood Glucose; Blood Pressure; Brain Ischemia; Cardiovascular Agents; Chi-Square Distribution; Databases, Factual; Diffusion Magnetic Resonance Imaging; Disability Evaluation; Female; Humans; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Patient Admission; Predictive Value of Tests; Protective Factors; Retrospective Studies; Risk Factors; Severity of Illness Index; Stroke

We sought to compare the benefit of percutaneous closure to that of medical therapy alone for the secondary prevention of embolism in patients with patent foramen ovale (PFO) and otherwise unexplained ischemic stroke, in a propensity scored study.. Between 2000 and 2012, we selected consecutive first-ever ischemic stroke patients aged 18 to 45 years with PFO and no other cause of brain ischemia, as part of the IPSYS registry (Italian Project on Stroke in Young Adults), who underwent either percutaneous PFO closure or medical therapy for comparative analysis. Primary end point was a composite of ischemic stroke, transient ischemic attack, or peripheral embolism. Secondary end point was brain ischemia. Five hundred and twenty-one patients qualified for the analysis. The primary end point occurred in 15 patients treated with percutaneous PFO closure (7.3%) versus 33 patients medically treated (10.5%; hazard ratio, 0.72; 95% confidence interval, 0.39-1.32; P=0.285). The rates of the secondary end point brain ischemia were also similar in the 2 treatment groups (6.3% in the PFO closure group versus 10.2% in the medically treated group; hazard ratio, 0.64; 95% confidence interval, 0.33-1.21; P=0.168). Closure provided a benefit in patients aged 18 to 36 years (hazard ratio, 0.19; 95% confidence interval, 0.04-0.81; P=0.026) and in those with a substantial right-to-left shunt size (hazard ratio, 0.19; 95% confidence interval, 0.05-0.68; P=0.011).. PFO closure seems as effective as medical therapy for secondary prevention of cryptogenic ischemic stroke. Whether device treatment might be more effective in selected cases, such as in patients younger than 37 years and in those with a substantial right-to-left shunt size, deserves further investigation.

Topics: Adolescent; Adult; Age Factors; Brain Ischemia; Cardiac Catheterization; Cardiovascular Agents; Chi-Square Distribution; Embolism, Paradoxical; Female; Foramen Ovale, Patent; Humans; Intracranial Embolism; Italy; Male; Middle Aged; Propensity Score; Proportional Hazards Models; Registries; Risk Factors; Secondary Prevention; Stroke; Time Factors; Treatment Outcome; Young Adult

Previous cross-sectional surveys in different European countries within the EUROASPIRE programme demonstrated a high prevalence of modifiable risk factors, unhealthy lifestyles and inadequate drug treatment in coronary heart disease patients. Comparable data for ischaemic stroke patients is lacking.. A stroke-specific study module was added to the EUROASPIRE III core survey. This cross-sectional multicentre survey included consecutive patients with first-ever ischaemic stroke from four European countries. Data were obtained from medical records, patient interviews and patient examinations within 6-36 months after the stroke event. Control of modifiable risk factors after stroke was evaluated against contemporary European guidelines.. A total of 881 patients was recruited. Median age was 66 years, 37.5% were female; average time from the stroke event to interview was 550 days. At the time of the interview, 17.6% of stroke patients smoked cigarettes, 35.5% had a body mass index ≥30 kg/m(2), 62.4% showed elevated blood pressure and 75.7% exhibited elevated LDL cholesterol levels. Antiplatelet drugs or oral anticoagulants were used by 87.2%, antihypertensive medication by 84.4% and statins by 56.8% of stroke patients. Among patients using antihypertensive drugs and lipid-lowering medication at the time of the interview, 34.3% and 34.4%, respectively, achieved target blood pressure and total cholesterol values according to current European guidelines.. The EUROASPIRE III stroke-specific module shows that secondary prevention and risk factor control in patients after ischaemic stroke need to be improved in four European centres at the time of the study since about half of patients are not achieving risk factor targets defined in European guidelines.

Topics: Aged; Brain Ischemia; Cardiovascular Agents; Comorbidity; Cross-Sectional Studies; Delivery of Health Care; Europe; Female; Guideline Adherence; Health Care Surveys; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Life Style; Male; Middle Aged; Practice Guidelines as Topic; Prevalence; Recurrence; Risk Assessment; Risk Factors; Risk Reduction Behavior; Secondary Prevention; Smoking; Smoking Cessation; Smoking Prevention; Stroke; Surveys and Questionnaires; Time Factors; Treatment Outcome; Weight Loss

No information exists, to our knowledge, about the possible role of cardiovascular drug administration in the acute phase of ischemic stroke and possible effects on stroke outcome. The aim of our study was to evaluate the relationship between in-hospital treatment with cardiovascular drugs in patients with acute ischemic stroke and some outcome indicators.. 1096 subjects enrolled in the GIFA study, who had a main discharge diagnosis of ischemic stroke represent the final sample. Drugs considered for the analysis were the following: ACE-inhibitors (ACEI), angiotensin II receptor blockers (ARBs), statins, calcium-channel-blockers (CCBs), antiplatelet (APL) drugs, antivitamin-k (VKAs), and heparins. As outcome indicators we choose in-hospital mortality, cognitive function evaluated by Hodkinson Abbreviated Mental Test (HAMT), and functional status evaluated by activity daily living (ADL). Indicators of a good outcome were: no in-hospital mortality, HAMT >6 and 0 ADL impaired. Patients with a good outcome showed a higher rate of in-hospital treatment with ACE-inhibitors, calcium-channel blockers and a lower rate of pre-treatment with heparin.. Our study suggests that if a patient with acute ischemic stroke has higher SBP at admission, higher total cholesterol plasma levels, a lower Charlson index and is treated with ACE-inhibitors, calcium channel blockers and antiplatelet drugs, the short term outcome is better in terms of in-hospital mortality and functional indicators such as cognitive and functional performance at discharge.

Topics: Activities of Daily Living; Aged; Angiotensin-Converting Enzyme Inhibitors; Brain Ischemia; Calcium Channel Blockers; Cardiovascular Agents; Cognition Disorders; Comorbidity; Female; Geriatric Assessment; Humans; Hypercholesterolemia; Hypertension; Italy; Male; Platelet Aggregation Inhibitors; Prognosis; Retrospective Studies; Stroke; Time Factors

Few studies have examined the role of cardiovascular drugs on acute ischaemic stroke prognosis.. To evaluate the relationship between a favourable outcome in patients with acute ischaemic stroke and specific demographic, clinical and laboratory variables and cardiovascular drug pretreatment.. The 1096 patients enrolled in the GIFA study (who had a main discharge diagnosis of ischaemic stroke) represent the final patient sample used in this analysis. Drugs considered in the analysis included angiotensin converting enzyme (ACE)-inhibitors, angiotensin II receptor blockers, statins, calcium channel blockers, anti-platelet drugs, vitamin K antagonists and heparins. The outcomes analyzed included in-hospital mortality, cognitive function evaluated by the Hodkinson Abbreviated Mental Test (HAMT), and functional status evaluated by activities of daily living (ADL). The definition of a good outcome was no in-hospital mortality, a HAMT score of ≥ 6 and no ADL impairment.. Patients with no in-hospital mortality, a HAMT score of >6 and no ADL impairment were more likely to be younger at baseline and have a lower blood glucose level and a systolic blood pressure (SBP) between 120 and 180 mmHg, a higher plasma total cholesterol level, a lower white blood cell count, and a lower Charlson Index (CI) score, a higher rate of pretreatment with ACE-inhibitors, calcium channel blockers and a lower rate of pretreatment with heparin.. Predictors of good outcome, in terms of in-hospital mortality and cognitive and functional performance at discharge, included higher SBP at admission between 120 and 180 mmHg, a SBP plasma total cholesterol levels, a lower CI score, and pretreatment with ACE-inhibitors, calcium channel blockers and anti-platelets.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Cardiovascular Agents; Databases, Factual; Female; Follow-Up Studies; Hospital Mortality; Humans; Italy; Male; Pharmacoepidemiology; Retrospective Studies; Stroke; Treatment Outcome

With the advent of new therapeutic options for acute ischemic stroke, expeditious evaluation of patients with suspected stroke has become imperative. Goals of the initial evaluation are to determine the time of symptom onset, severity of the neurologic deficit, and to exclude intracranial hemorrhage and other mimics of acute ischemic stroke. CT and MRI perfusion studies may demonstrate the presence of an ischemic penumbra and aid in identification of patients who may benefit from thrombolysis. Intravenous recombinant tissue plasminogen activator (IV rtPA) remains the gold standard for acute ischemic stroke treatment, and the therapeutic time window recently has been extended to 4.5 h in certain patients. Catheter-based intra-arterial thrombolysis is being used increasingly as "rescue therapy" after IV rtPA and as primary therapy in select patients who are ineligible for intravenous therapy. Trials investigating the efficacy and safety of intra-arterial therapy are ongoing.

Topics: Brain Ischemia; Cardiovascular Agents; Emergencies; Fibrinolytic Agents; Humans; Stroke; Telemedicine; Tissue Plasminogen Activator

Cerebralcare Granule (CG) is a Chinese herb compound preparation that has been used for treatment of cerebrovascular related diseases. However, the effect of post-treatment with CG on ischemia and reperfusion (I/R) induced cerebral injury is so far unclear.. In present study, cerebral global I/R was induced in Mongolian gerbils by clamping bilateral carotid arteries for 30 min followed by reperfusion for 5 days, and CG (0.4 g/kg or 0.8 g/kg) was administrated 3h after the initiation of reperfusion.. Post-treatment with CG for 5 days attenuated the I/R-induced production of hydrogen peroxide in, leukocyte adhesion to, and albumin leakage from cerebral microvessels, and, meanwhile, protected neuron from death, reduced the number of caspase-3- and Bax-positive cells, and increased Bcl-2-positive cells in hippocampal CA1 region.. The results suggest that CG given after initiation of reperfusion is able to ameliorate cerebral microvascular dysfunction and hippocampal CA1 neuron damage caused by I/R.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Brain Ischemia; CA1 Region, Hippocampal; Capillary Permeability; Cardiovascular Agents; Caspase 3; Cerebral Veins; Cerebrovascular Circulation; Disease Models, Animal; Drugs, Chinese Herbal; Gerbillinae; Hydrogen Peroxide; Leukocyte Rolling; Male; Microcirculation; Neurons; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Reperfusion Injury; Serum Albumin; Venules

The extent and implications of age- and sex-related differences in prophylaxis following ischemic stroke are unknown. We examined differences in the use of medical prophylaxis across age and sex groups in stroke patients after hospital discharge in Denmark and estimated the possible impact on age- and sex-related differences in mortality.. A nationwide population-based follow-up study was conducted involving 28,634 patients hospitalized for ischemic stroke in 2003-2006 who survived 30 days after discharge. The proportion of patients who filled prescriptions for cardiovascular drugs within 0-6 and 12-18 months after discharge was determined. Mortality rates were compared across age and sex groups with and without controlling for use of medical prophylaxis.. Increasing age was associated with lower prophylaxis. Adjusted odds ratios for the use of a combination of a platelet inhibitor, an antihypertensive and a statin were 0.45 [95% confidence interval (CI): 0.38-0.54] and 0.52 (95% CI: 0.43-0.62) for men and women >80 years, respectively, compared with men ≤65 years. No systematic sex-related differences were identified. Continued drug use ranged from 66.1 to 91.9% for different drugs 12-18 months after discharge, with the lowest rate of continued use found among patients >80 years. Controlling for use of medical prophylaxis was associated with lower mortality rate ratios for elderly compared with younger patients.. Continuous efforts are warranted to ensure implementation of evidence-based secondary prophylaxis among elderly patients with ischemic stroke.

Topics: Age Factors; Aged; Aged, 80 and over; Brain Ischemia; Cardiovascular Agents; Denmark; Drug Prescriptions; Evidence-Based Medicine; Female; Follow-Up Studies; Hospitalization; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Patient Discharge; Practice Guidelines as Topic; Proportional Hazards Models; Prospective Studies; Registries; Risk Assessment; Risk Factors; Secondary Prevention; Sex Factors; Stroke; Time Factors; Treatment Outcome

Most studies that have reported on the progression of ipsilateral and/or contralateral internal carotid artery (ICA) stenosis are restricted to a few years.. Based on a single-center carotid endarterectomy (CEA) registry, we sought all patients with CEA for symptomatic high-grade ICA stenosis between 1970 and 2002. 361 CEA patients (mean age 66 years, 73% male) with annual carotid ultrasound and clinical follow-up were identified. Kaplan-Meier analysis was used to estimate the occurrence of (i) progressive ICA stenosis or restenosis of either the operated or contralateral side, and (ii) cerebrovascular events over time of either the operated or contralateral side.. Progressive ICA disease was more likely on the contralateral than on the ipsilateral ICA (hazard ratio 2.71; CI 1.8-4.1, p < 0.001). After 5 years, the probability for progressive ICA disease was 5.2% for the ipsilateral versus 15.8% for the contralateral ICA. After 15 years, the likelihood was 37% for both sides. In the presence of progressive restenosis of the ipsilateral ICA, the 20-year probability of further ischemic cerebrovascular events was 50% compared to 18% in patients without ICA disease progression. For the contralateral ICA, the probability of further ischemic events was 24.5% in patients with ICA disease progression compared to 9.6% without ICA disease progression (15 years).. 15 years after CEA, one third of the patients can be expected to develop progressive ICA disease. While ICA disease progression seems to be more prominent on the contralateral ICA within the first years, this difference fades out after 15 years. One out of 2 patients with ipsilateral ICA disease progression can be expected to have a recurrent cerebral ischemic event within 15 years. It remains to be determined whether consequent application of high-dose statins, optimal blood pressure management and antithrombotic therapy can reduce this rate.

Topics: Adult; Aged; Aged, 80 and over; Brain Ischemia; Cardiovascular Agents; Carotid Stenosis; Comorbidity; Disease Progression; Endarterectomy, Carotid; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Postoperative Complications; Recurrence; Registries; Risk Factors; Switzerland; Time Factors; Ultrasonography, Doppler, Color

There have now been numerous phase III trials of neuroprotection that have failed to live up to the expectations created by preclinical testing in animal models, the most recent of which was the second pivotal trial of the spin trap agent NXY-059. We have reached a stage at which research in this area should stop altogether or radical new approaches adopted. The purpose of this article is to review how we reached this stage and make recommendations for a new approach to neuroprotection research.. The background to neuroprotection research is reviewed and its problems are highlighted based on the research of others and of our own research group. From this, a series of questions are posed that require answers if the field is to progress. A road map for future research is then proposed.. The road map involves the following steps for putative neuroprotectants: (1) better proof of efficacy in animal models; (2) in vivo evidence of efficacy in human tissue using cell cultures or brain slices; (3) in vivo studies of their distribution in the normal and ischemic human brain, particularly focusing on the ischemic penumbra; (4) demonstration of efficacy in novel human models of cerebral ischemia; and (5) phase II and III clinical trails with penumbral selection using imaging techniques.. The accumulated evidence suggests that neuroprotection failure in clinical trial is due to identifiable preclinical and clinical factors. Neuroprotection research should be pursued but with a very different and more rigorous approach.

Topics: Animals; Benzenesulfonates; Brain Ischemia; Cardiovascular Agents; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Disease Models, Animal; Free Radical Scavengers; Humans; Neuroprotective Agents; Stroke

Much effort has been made to study first-ever stroke patients. However, recurrent stroke has not been investigated as extensively. It is unclear which risk factors dominate, and whether adequate secondary prevention has been provided to patients who suffer from recurrent stroke. Also, the different types of recurrent stroke need further evaluation.. The study included patients with recurrent stroke admitted to twenty-three Swedish stroke centers. The type of previous and recurrent stroke was determined, as well as evaluation (when applicable) of recurrent ischemic stroke according to the TOAST classification. Presence of vascular risk factors was registered and compared to the type of stroke. Also assessed was ongoing secondary prevention treatment at recurrent stroke onset.. A total of 889 patients with recurrent stroke (mean age 77) were included in the study. Of these, 805 (91%) had ischemic stroke, 78 (9%) had intracerebral hemorrhage and 6 (<1%) stroke of unknown origin. The most frequent vascular risk factors were hypertension (75%) and hyperlipidemia (56%). Among the 889 patients, 29% had atrial fibrillation. Of the patients in the ischemic group with cardiac embolism, only 21% were on anticoagulation treatment. The majority of the patients (75%) had their most recent previous stroke >12 months before admission.. Few patients had a recurrent stroke shortly after the previous stroke in this study. This indicates that it is meaningful to prevent a second event with an adequate long-term treatment strategy for secondary prevention after first-ever stroke. There also seems to be a clear potential for improving secondary prevention after stroke.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antihypertensive Agents; Atrial Fibrillation; Brain Ischemia; Cardiovascular Agents; Cerebral Hemorrhage; Diabetes Complications; Embolism; Female; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Odds Ratio; Platelet Aggregation Inhibitors; Registries; Risk Assessment; Risk Factors; Secondary Prevention; Smoking; Stroke; Sweden; Time Factors; Treatment Outcome

Topics: Animals; Brain Ischemia; Cardiovascular Agents; Humans; Interleukin 1 Receptor Antagonist Protein; Stroke

We describe a postpartum woman who, after an uneventful pregnancy, developed posterior reversible encephalopathy syndrome after spinal anesthesia, complicated by postdural puncture headache.

Topics: Adult; Anesthesia, Spinal; Brain Edema; Brain Ischemia; Cardiovascular Agents; Cesarean Section; Diffusion Magnetic Resonance Imaging; Female; Humans; Magnesium Sulfate; Magnetic Resonance Angiography; Post-Dural Puncture Headache; Postpartum Period; Pregnancy; Syndrome; Treatment Outcome; Vasospasm, Intracranial

Topics: Acute Disease; Benzenesulfonates; Brain Ischemia; Cardiovascular Agents; Data Interpretation, Statistical; Hemorrhage; Humans; Nitrogen Oxides; Stroke

Topics: Acute Disease; Benzenesulfonates; Brain Ischemia; Cardiovascular Agents; Data Interpretation, Statistical; Humans; Nitrogen Oxides; Stroke

Topics: Acute Disease; Brain Edema; Brain Ischemia; Cardiovascular Agents; Case Management; Combined Modality Therapy; Decompression, Surgical; Fever; Humans; Hyperglycemia; Hypertension; Hypoxia; Intracranial Hypertension; Pneumonia; Thrombolytic Therapy; Urinary Tract Infections; Water-Electrolyte Imbalance

Atherothrombosis is a systemic disease affecting coronary, cerebral, and lower limb arteries, and requiring secondary prevention measures.. Data from three observational studies carried out in 1999-2000 (ECLAT1, APRES, PRISMA) were pooled to describe the prevalence of cardiovascular risk factors and the patterns of drug use in atherothrombotic patients.. General practitioners and cardiologists engaged in a private practice and evenly distributed in France recruited consecutive patients who had a history of at least one atherothrombotic event: myocardial infarction (MI), ischaemic stroke, and/or peripheral arterial disease (PAD).. The sample was composed of 14 544 patients (men: 75.0%, age 75 or older: 31.0%). At least one of the four major risk factors (smoking, hypertension, hypercholesterolaemia, diabetes) was present in 94.3% of the sample. Prevalence of drug use was: 78.8% (antiplatelet agents), 48.5% (statins), 36.7% (beta-blockers), and 33.4% [angiotensin-converting enzyme (ACE) inhibitors]. After adjustment for confounders, statins were taken in a significantly larger extent in patients with a history of isolated MI than in those with a previous ischaemic stroke or PAD, or in patients who suffered from both MI and ischaemic stroke. Isolated MI (as compared with ischaemic stroke and PAD) was significantly and independently associated with a higher probability to take antiplatelet agents, beta-blockers or ACE inhibitors.. At least one conventional risk factor was observed in almost all atherothrombotic patients. Use of preventive drugs was lower in patients with a history of ischaemic stroke or PAD, and should increase, accordingly to the results of recent randomized controlled trials.

Topics: Adult; Aged; Brain Ischemia; Cardiovascular Agents; Diabetes Mellitus, Type 2; Female; France; Humans; Hypercholesterolemia; Hypertension; Life Style; Male; Middle Aged; Myocardial Infarction; Peripheral Vascular Diseases; Prevalence; Risk Factors; Smoking; Stroke

The information on the existence of sex differences in management of stroke patients is scarce. We evaluated whether sex differences may influence clinical presentation, resource use, and outcome of stroke in a European multicenter study.. In a European Concerted Action involving 7 countries, 4499 patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, and 3-month survival, disability (Barthel Index), and handicap (Rankin Scale).. Overall, 2239 patients were males and 2260 females. Compared with males, female patients were significantly older (mean age 74.5+/-12.5 versus 69.2+/-12.1 years), more frequently institutionalized before stroke, and with a worse prestroke Rankin score (all values P<0.001). History of hypertension (P=0.007) and atrial fibrillation (P<0.001) were significantly more frequent in female stroke patients, as were coma (P<0.001), paralysis (P<0.001), aphasia (P=0.001), swallowing problems (P=0.005), and urinary incontinence (P<0.001) in the acute phase. Brain imaging, Doppler examination, echocardiogram, and angiography were significantly less frequently performed in female than male patients (all values P<0.001). The frequency of carotid surgery was also significantly lower in female patients (P<0.001). At the 3-month follow-up, after controlling for all baseline and clinical variables, female sex was a significant predictor of disability (odds ratio [OR], 1.41; 95% CI 1.10 to 1.81) and handicap (OR, 1.46; 95% CI 1.14 to 1.86). No significant gender effect was observed on 3-month survival.. Sex-specific differences existed in a large European study of hospital admissions for acute stroke. Both medical and sociodemographic factors may significantly influence stroke outcome. Knowledge of these determinants may positively impact quality of care.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alcohol Drinking; Atrial Fibrillation; Brain Damage, Chronic; Brain Ischemia; Cardiovascular Agents; Case Management; Comorbidity; Diabetes Mellitus; Diagnostic Imaging; Europe; Female; Follow-Up Studies; Glasgow Coma Scale; Humans; Hypertension; Hypoglycemic Agents; Institutionalization; Length of Stay; Male; Middle Aged; Myocardial Infarction; Patient Discharge; Prognosis; Registries; Risk Factors; Severity of Illness Index; Sex Factors; Smoking; Stroke; Stroke Rehabilitation; Subarachnoid Hemorrhage; Survival Analysis; Treatment Outcome

Changes in hemorheological parameters were studied in patients with ischemic cerebrovascular disease and elderly healthy men who ingested ethanol at 0.5 and 1 g/kg body weight. Following ingestion of 1 g/kg, but not 0.5 g/kg of ethanol, there were significant changes in hemorheologic factors. Whole blood viscosity (WBV, shear rate: 18.8, 37.5, 75, 150, 350 sec(-1)) and blood viscosity corrected for hematocrit (BVC) were increased. WBV and BVC at high shear rate were increased and red blood cell deformability impaired in patients with ischemic cerebrovascular disease, while those factors were not significantly changed in healthy men. It is considered that ethanol ingestion could has bad influences for the microcirculation in patients with ischemic cerebrovascular disease.

Topics: Acetaldehyde; Aged; Alcohol Drinking; Blood Proteins; Blood Viscosity; Brain Ischemia; Cardiovascular Agents; Cerebral Infarction; Diuresis; Dose-Response Relationship, Drug; Erythrocyte Deformability; Ethanol; Hematocrit; Hemodynamics; Hemorheology; Humans; Hyperlipidemias; Hypertension; Male; Microcirculation; Middle Aged

Topics: Acute Disease; Brain Ischemia; Cardiovascular Agents; Cerebrovascular Disorders; Humans; Piperidines; Thiazoles

Although platelets constitute the major component of a thrombus, its role in determining the clinical severity of thrombotic stroke is unknown. Therefore, we investigated the relationship between platelet ionized calcium ([Ca2+i]), a measure of platelet activity and presumably proneness to thrombosis, and clinical stroke severity in 45 consecutively studied acute ischemic stroke patients. Even though there was no correlation between the clinical neurological scores and the levels of baseline and activated platelet [Ca2+i], stroke was less severe in patients who had been taking aspirin at the time of stroke onset. These results raise several important questions: (a) is the extent of platelet activation a reflection of thrombus volume, (b) does the clinical severity of neurological deficit reflect the causative thrombus volume, and (c) whether the beneficial effect of aspirin in stroke prophylaxis is through its inhibition of platelets alone.

Topics: Aged; Aspirin; Blood Platelets; Brain Ischemia; Calcium; Cardiovascular Agents; Collagen; Disease Susceptibility; Drug Interactions; Female; Fibrinolytic Agents; Humans; Hypoglycemic Agents; Ibuprofen; Male; Middle Aged; Platelet Activation; Severity of Illness Index; Thrombin

A study is presented of the clinico-hemodynamic efficacy of mildronate in 38 patients with ischemic stroke. The drug produces a positive inotropic effect on the myocardium, improves the cerebral hemodynamics in patients with stroke and postischemic hypo- and hyperperfusion of the brain tissue. It is concluded that mildronate may be recommended for the complex treatment of ischemic disorders of the cerebral circulation.

Topics: Aged; Brain Ischemia; Cardiovascular Agents; Drug Evaluation; Female; Hemodynamics; Humans; Male; Methylhydrazines; Middle Aged; Remission Induction; Time Factors

Influence of drugs on the changes of extracellular potassium ion concentration in the brain during total cerebral ischaemia was investigated. The aorta of the dogs was clamped twice with an intermittent reperfusion period of 60 min. In control experiments no significant difference was found in the elevation of extracellular potassium ion concentration of the brain during the first and second clampings. In the present study drugs were administered 10 min prior the second aorta occlusion. Verapamil in a dose of 0.125 mg/kg proved to be ineffective. Piridoxilate in a dose of 10 mg/kg and piracetam in a dose of 100 mg/kg delayed to a small extent the potassium outflow. The following drugs enhanced significantly the duration before the steep increase of potassium ion outflow: phenytoin in a dose of 10 mg/kg by 31.8 sec (p less than 0.01), ethyl-butyl-thiobarbital in a dose of 15 mg/kg by 30.2 sec (p less than 0.05), and lidocaine in a dose of 100 mg/kg by 115.8 sec (p less than 0.01). Comparing present results to our earlier data (obtained after 50 sec ischaemia) it can be concluded, that these protective influences become more effective during longer ischaemic period (2-5 min), when lidocaine, phenytoin and ethyl-butyl-thiobarbital were used. Moreover, in spite of the observation seen during shorter ischaemia, even piridoxilate and piracetam exerted some degree of protective effect. No such effect of verapamil could be detected in the present experimental model.

Topics: Animals; Blood Pressure; Brain; Brain Ischemia; Cardiovascular Agents; Dogs; Electroencephalography; Microelectrodes; Potassium; Reperfusion

E2001 (2-(4-(p-fluorobenzoyl)-piperidin-1-yl)-2'-acetonaphthone hydrochloride, CAS 107025-80-9) is a novel anti-ischemic agent, which is reported to protect against delayed neuronal death in the CA1 subfield of the hippocampus. The effect of E2001 on ischemia-induced impairment of the passive avoidance response in gerbils was studied. The passive avoidance response was not disturbed by transient cerebral ischemia of 3 min duration, but was impaired by 5-min ischemia. E2001 at oral doses of 3 and 10 mg/kg significantly improved the impaired passive avoidance response induced by 5-min cerebral ischemia. It is speculated that the improvement by E2001 may be partly due to the inhibition of extracellular glutamate accumulation, and the suppression of lipid peroxides formation during cerebral ischemia.

Topics: Animals; Avoidance Learning; Brain Ischemia; Cardiovascular Agents; Electroshock; Female; Gerbillinae; Lipid Peroxides; Naphthalenes; Piperidines

The protective effect of E-2001 (2-(4-(p-fluorobenzoyl)-piperidin-1-yl)-2'-acetonaphthone hydrochloride) was examined in various ischemic models, and the mechanisms of its action were investigated in vitro and in vivo. 1. Pretreatment with E-2001 ameliorated the degeneration of pyramidal neurons in the hippocampal CA1 sector following transient ischemia in Mongolian gerbils. 2. E-2001 improved stroke symptoms induced by permanent unilateral carotid artery ligation in gerbils. 3. E-2001 prolonged the survival time following permanent bilateral carotid artery ligation in gerbils and mice. E-2001 also prolonged the survival time following intravenous injection of KCN into mice. 4. E-2001 suppressed the high potassium-evoked release of glutamate from rat hippocampal slices. Furthermore, E-2001 prevented the excessive accumulation of extracellular glutamate induced by a brief ischemia in gerbils. 5. E-2001 exerted calcium antagonistic action, i.e., a relaxing effect on high potassium-induced contraction of rat aorta. 6. E-2001 exerted inhibitory action on the lipoperoxide production in vitro and in vivo, and exhibited a radical scavenging effect against O- and N-radicals. These results suggest that E-2001 might be effective as a novel anti-ischemic agent.

Topics: Animals; Brain Ischemia; Cardiovascular Agents; Female; Free Radicals; Gerbillinae; Glutamates; Hippocampus; Ischemia; Lipid Peroxides; Male; Mice; Muscle Contraction; Muscle, Smooth, Vascular; Naphthalenes; Neurons; Piperidines; Potassium; Potassium Cyanide; Rats

Topics: Aged; Antihypertensive Agents; Brain Ischemia; Cardiovascular Agents; Disease; Hypertension; Muscle Relaxants, Central; Secologanin Tryptamine Alkaloids; Sympatholytics