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Sample records for ischemic myocardiopathy trasplante

  1. AUGMENTATION OF THE VIRULENCE OF MURINE COXSACKIE-VIRUS B-3 MYOCARDIOPATHY BY EXERCISE

    PubMed Central

    Gatmaitan, Bienvenido G.; Chason, Jacob L.; Lerner, A. Martin

    1970-01-01

    Coxsackievirus B-3 myocardiopathy was induced in weanling mice by intraperitoneal and intracerebral inoculations of the Nancy strain. Acute mortality was 5.5%. The cardiomyopathy is characterized by an early phase lasting about 9 days with myocardial necrosis, associated inflammation, and healing by fibrosis and calcification involving 25 to 50% of the contractile fibers in each affected mouse. Infectious coxsackievirus may be recovered from the heart during this phase. Continuing myocardial inflammatory lesions follow during the later phase, but infectious virus is no longer present. When mice were forced to swim in a preheated pool (33°C) during both phases of their myocardiopathy, virulence was strikingly augmented. Fully half of the mice died of congestive failure, the majority while swimming. Hearts were dilated, hypertrophied, and grossly necrotic. The myocardium was transformed to a completely necrotic, inflammatory, calcifying mass. At the peak of the infectious phase, myocardial replication of coxsackievirus was increased 530 times in nurslings which had been forced to swim. Myositis in hind limbs was more frequent, and inflammatory lesions in perirenal and pericardial fat were more severe in the mice which were forced to swim. When swimming was begun on the 9th day after infection, the virulence and lethality (13.8%) of infection were moderately increased. PMID:4246139

  2. Augmentation of the virulence of murine coxsackie-virus B-3 myocardiopathy by exercise.

    PubMed

    Gatmaitan, B G; Chason, J L; Lerner, A M

    1970-06-01

    Coxsackievirus B-3 myocardiopathy was induced in weanling mice by intraperitoneal and intracerebral inoculations of the Nancy strain. Acute mortality was 5.5%. The cardiomyopathy is characterized by an early phase lasting about 9 days with myocardial necrosis, associated inflammation, and healing by fibrosis and calcification involving 25 to 50% of the contractile fibers in each affected mouse. Infectious coxsackievirus may be recovered from the heart during this phase. Continuing myocardial inflammatory lesions follow during the later phase, but infectious virus is no longer present. When mice were forced to swim in a preheated pool (33 degrees C) during both phases of their myocardiopathy, virulence was strikingly augmented. Fully half of the mice died of congestive failure, the majority while swimming. Hearts were dilated, hypertrophied, and grossly necrotic. The myocardium was transformed to a completely necrotic, inflammatory, calcifying mass. At the peak of the infectious phase, myocardial replication of coxsackievirus was increased 530 times in nurslings which had been forced to swim. Myositis in hind limbs was more frequent, and inflammatory lesions in perirenal and pericardial fat were more severe in the mice which were forced to swim. When swimming was begun on the 9th day after infection, the virulence and lethality (13.8%) of infection were moderately increased.

  3. [Anaesthetic management of caesarean section in pregnancy with diabetes and hypertrophic myocardiopathy with restrictive diastolic dysfunction].

    PubMed

    Holgado, C M; Coves, S

    2013-02-01

    Haemodynamic changes that occur during pregnancy are maximal between 28 and 34 weeks. In the pregnant woman with several associated diseases, such as hypertensive myocardiopathy and pre-gestational diabetes, these changes can lead to a difficult control of pulmonary hypertension and acute pulmonary oedema. We report the case of a pregnant woman with long term type 1 diabetes mellitus who suffered pre-eclampsia in a previous pregnancy, and since then developed hypertensive cardiomyopathy. She was admitted at 30 week gestation for metabolic and blood pressure control, and developed congestive cardiac failure after the administration of betamethasone for foetal lung maturity. A transthoracic echocardiogram showed a non-dilated hypertrophic left ventricle with good systolic function, restrictive diastolic dysfunction and moderate pulmonary arterial hypertension. When her general condition improved, we performed a caesarean section under regional anaesthesia to prevent the complications of pulmonary and systemic hypertension. We present the anaesthetic management and resolution of complications after oxytocin administration.

  4. Cardiac involvement in acromegaly: specific myocardiopathy or consequence of systemic hypertension?

    PubMed

    López-Velasco, R; Escobar-Morreale, H F; Vega, B; Villa, E; Sancho, J M; Moya-Mur, J L; García-Robles, R

    1997-04-01

    To evaluate the relative contributions of past or present GH hypersecretion and of hypertension to the cardiac abnormalities present in acromegaly, we have studied the serum GH and insulin-like growth factor I concentrations, systolic and diastolic blood pressures, and morphological and functional cardiac indexes as measured by echocardiography-Doppler, in 39 patients with active or cured acromegaly, 16 hypertensive controls, and 17 normotensive controls. Hypertension was present in 42.8% of patients with active acromegaly and in 28.0% of patients in which acromegaly was cured. Hypertension was independently related to an increase in indexes of cardiac morphology (left ventricular mass, left ventricular posterior wall thickness, interventricular septum thickness, relative wall thickness with respect to the diastolic diameter of the left ventricle, and left atrial end-systolic diameter), systolic function (stroke volume, fractional shortening, and end-systolic stress), and diastolic function (isovolumic relaxation time and maximal late diastolic flow velocity) and to a reduction in the early to late maximal diastolic flow velocity ratio. Acromegaly was related to an increase in left ventricular mass, stroke volume, cardiac output, and isovolumic relaxation time, which were independent from the presence of hypertension. End-systolic stress was reduced by acromegaly. In the five patients in which active acromegaly was successfully treated, left ventricular mass and left ventricular posterior wall thickness were reduced 1 yr later. In conclusion, the asymptomatic morphological and functional cardiac abnormalities present in acromegalic patients are independently related to acromegaly and hypertension, pointing to the existence to a specific acromegalic myocardiopathy that might be aggravated by the coexistence of hypertension.

  5. Ischemic Colitis

    PubMed Central

    Montessori, Gino; Liepa, Egils V.

    1970-01-01

    Twenty cases of ischemic colitis are reviewed; 19 were obtained from autopsy files and the diagnosis in one was made from a surgical specimen. The majority of the patients were elderly with generalized arteriosclerosis. In approximately two-thirds of the patients the ischemic colitis was precipitated by preceding trauma, operation or congestive heart failure. Clinically, ischemic colitis is characterized by abdominal pain, distension and bleeding per rectum. Perforation of large bowel may occur. The lesions tend to be localized around the splenic flexure and junction of the descending and sigmoid colon, and in cases following aortic graft surgery the rectum is involved. Microscopically, there is necrosis, hemorrhage and ulceration. In less severe cases the mucosa only is affected. Cases with perforation show necrosis of all layers. It is considered that ischemic colitis is comparatively frequent and should be distinguished from other inflammatory conditions of the colon. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7FIG. 8FIG. 9 PMID:5308923

  6. Ischemic Colitis

    PubMed Central

    FitzGerald, James F.; Hernandez III, Luis O.

    2015-01-01

    Most clinicians associate ischemic colitis with elderly patients who have underlying cardiovascular comorbidities. While the majority of cases probably occur in this population, the disease can present in younger patients as a result of different risk factors, making the diagnosis challenging. While a majority of patients respond to medical management, surgery is required in approximately 20% of the cases and is associated with high morbidity and mortality. PMID:26034405

  7. Prevention of ventricular fibrillation, acute myocardial infarction (myocardial necrosis), heart failure, and mortality by bretylium: is ischemic heart disease primarily adrenergic cardiovascular disease?

    PubMed

    Bacaner, Marvin; Brietenbucher, James; LaBree, John

    2004-01-01

    It is widely, but mistakenly, believed that ischemic heart disease (IsHD) and its complications are the sole and direct result of reduced coronary blood flow by obstructive coronary artery disease (CAD). However, cardiac angina, acute myocardial infarction (AMI), and sudden cardiac death (SCD) occur in 15%-20% of patients with anatomically unobstructed and grossly normal coronaries. Moreover, severe obstructive coronary disease often occurs without associated pathologic myocardiopathy or prior symptoms, ie, unexpected sudden death, silent myocardial infarction, or the insidious appearance of congestive heart failure (CHF). The fact that catecholamines explosively augment oxidative metabolism much more than cardiac work is generally underappreciated. Thus, adrenergic actions alone are likely to be more prone to cause cardiac ischemia than reduced coronary blood flow per se. The autonomic etiology of IsHD raises contradictions to the traditional concept of anatomically obstructive CAD as the lone cause of cardiac ischemia and AMI. Actually, all the signs and symptoms of IsHD reflect autonomic nervous system imbalance, particularly adrenergic hyperactivity, which may by itself cause ischemia as in rest angina. Adrenergic activity causing ischemia signals cardiac pain to pain centers via sympathetic efferent pathways and tend to induce arrhythmogenic and necrotizing ischemic actions on the cardiovascular system. This may result in ischemia induced metabolic myocardiopathy not unlike that caused by anatomic or spasmogenic coronary obstruction. The clinical study and review presented herein suggest that adrenergic hyperactivity alone without CAD can be a primary cause of IsHD. Thus, adrenergic heart disease (AdHD), or actually adrenergic cardiovascular heart disease (ACVHD), appears to be a distinct entity, most commonly but not necessarily occurring in parallel with CAD. CAD certainly contributes to vulnerability as well as the progression of IsHD. This vicious cycle

  8. Ischemic Strokes (Clots)

    MedlinePlus

    ... Infographic Stroke Hero F.A.S.T. Quiz Ischemic Strokes (Clots) Updated:Apr 26,2017 Ischemic stroke accounts ... strokes. Read more about silent strokes . TIA and Stroke: Medical Emergencies When someone has shown symptoms of ...

  9. [Constrictive pericarditis and restrictive myocardiopathy].

    PubMed

    Espínola Zavaleta, N; Maribel Vogel, L; Isaac Tazar, J; Yánac Chávez, P; Romero Cárdenas, A; Vargas Barrón, J

    1999-01-01

    The purpose of this study was to assess the clinical and echocardiographic characteristics of constrictive pericarditis (CP) and restrictive cardiomyopathy (RC) and to compare them with the results obtained with cardiac catheterization. Clinical history, electrocardiogram and X-ray were taken in all patients, and transthoracic and transesophageal echocardiography were performed. Cardiac catheterization with transmyocardial biopsy was performed on only 5 patients. Wall thickness and left ventricular dimensions were normal in all patients with CP. Wall thickness was increased in those with RC. No patients demonstrated alterations in segmental wall movement. The pericardium was thickened and abnormally bright in the 3 patients with CP. In patients with CP the percentage of atrioventricular, semilunar, pulmonary and hepatic flow changes with respiration were more than 10%. In patients with RC this flow variation was less notable. However, the percentage of systolic and diastolic flow velocity increase of hepatic veins during expiration was greater than in CP. We can conclude that M-mode, two dimensional and Doppler echocardiography is extremely useful noninvasive method to differentiate CP and RC with good correlation with cardiac catheterization.

  10. Recurrence of ANCA-associated vasculitis in a patient with kidney trasplant.

    PubMed

    García Cosmes, Pedro; Fraile Gómez, Pilar; Lewczuk, Kamil; Rodríguez González, Marta; Ruiz Ferreras, Elena; Tabernero Fernández, Guadalupe

    2016-01-01

    Renal disease secondary to vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA) can lead to chronic renal disease requiring renal replacement therapy. In these patients, kidney transplantation offers excellent long-term rates of allograft and patient survival; consequently, they can be trasplanted when the clinical disease activity has remitted. However, the risk of disease relapses in the renal allograft remains, although at lower rates due to modern immunosuppressive regimens. We describe the case of a male patient with extracapillary glomerulonephritis type III C-ANCA (+) who developed a recurrence in the renal allograft 8 years after transplantation. Intensive immunosupression with plasmapheresis controlled the disease. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Transient Ischemic Attack

    MedlinePlus

    A transient ischemic attack (TIA) is a stroke lasts only a few minutes. It happens when the blood supply to part of the brain is briefly blocked. Symptoms of a TIA are like other stroke symptoms, but do not ...

  12. Lubiprostone induced ischemic colitis.

    PubMed

    Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

    2013-01-14

    Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding.

  13. Ischemic Colitis Revealing Polyarteritis Nodosa

    PubMed Central

    Hamzaoui, Amira; Litaiem, Noureddine; Smiti Khanfir, M.; Ayadi, Sofiene; Nfoussi, Haifa; Houman, M. H.

    2013-01-01

    Ischemic colitis is one of the most common intestinal ischemic injuries. It results from impaired perfusion of blood to the bowel and is rarely caused by vasculitis. We report a case of ischemic colitis revealing polyarteritis nodosa (PAN) in a 55-year-old man. Histological examination of the resected colon led to the diagnosis of PAN. PMID:24382967

  14. Ischemic Nerve Block.

    ERIC Educational Resources Information Center

    Williams, Ian D.

    This experiment investigated the capability for movement and muscle spindle function at successive stages during the development of ischemic nerve block (INB) by pressure cuff. Two male subjects were observed under six randomly ordered conditions. The duration of index finger oscillation to exhaustion, paced at 1.2Hz., was observed on separate…

  15. Ischemic Nerve Block.

    ERIC Educational Resources Information Center

    Williams, Ian D.

    This experiment investigated the capability for movement and muscle spindle function at successive stages during the development of ischemic nerve block (INB) by pressure cuff. Two male subjects were observed under six randomly ordered conditions. The duration of index finger oscillation to exhaustion, paced at 1.2Hz., was observed on separate…

  16. Ischemic optic neuropathy.

    PubMed

    Hayreh, Sohan Singh

    2009-01-01

    Ischemic optic neuropathy is one of the major causes of blindness or seriously impaired vision, yet there is disagreement as to its pathogenesis, clinical features and especially its management. This is because ischemic optic neuropathy is not one disease but a spectrum of several different types, each with its own etiology, pathogenesis, clinical features and management. They cannot be lumped together. Ischemic optic neuropathy is primarily of two types: anterior (AION) and posterior (PION), involving the optic nerve head (ONH) and the rest of the optic nerve respectively. Furthermore, both AION and PION have different subtypes. AION comprises arteritic (A-AION - due to giant cell arteritis) and, non-arteritic (NA-AION - due to causes other than giant cell arteritis); NA-AION can be further classified into classical NA-AION and incipient NA-AION. PION consists of arteritic (A-PION - due to giant cell arteritis), non-arteritic (NA-PION - due to causes other than giant cell arteritis), and surgical (a complication of several systemic surgical procedures). Thus, ischemic optic neuropathy consists of six distinct types of clinical entities. NA-AION is by far the most common type and one of the most prevalent and visually crippling diseases in the middle-aged and elderly. A-AION, though less common, is an ocular emergency and requires early diagnosis and immediate treatment with systemic high dose corticosteroids to prevent further visual loss, which is entirely preventable. Controversy exists regarding the pathogenesis, clinical features and especially management of the various types of ischemic optic neuropathy because there are multiple misconceptions about its many fundamental aspects. Recently emerging information on the various factors that influence the optic nerve circulation, and also the various systemic and local risk factors which play important roles in the development of various types of ischemic optic neuropathy have given us a better understanding of

  17. Ischemic Amnesia: Causes and Outcome.

    PubMed

    Michel, Patrik; Beaud, Valérie; Eskandari, Ashraf; Maeder, Philippe; Demonet, Jean-François; Eskioglou, Elissavet

    2017-08-01

    We aimed to describe the frequency and characteristics of acute ischemic stroke and transient ischemic attacks presenting predominantly with amnesia (ischemic amnesia) and to identify clinical clues for differentiating them from transient global amnesia (TGA). We retrospectively analyzed and described all patients presenting with diffusion-weighted imaging magnetic resonance imaging-confirmed acute ischemic stroke/transient ischemic attacks with antero- and retrograde amnesia as the main symptom over a 13.5-year period. We also compared their clinical features and stroke mechanisms with 3804 acute ischemic stroke from our ischemic stroke registry. Thirteen ischemic amnesia patients were identified, representing 0.2% of all patients with acute ischemic stroke/transient ischemic attack. In 69% of ischemic amnesia cases, amnesia was transient with a median duration of 5 hours. Ischemia was not considered in 39% of cases. Fifty-four percent of cases were clinically difficult to distinguish from TGA, including 15% who were indistinguishable from TGA. 1.2% of all presumed TGA patients at our center were later found to have ischemic amnesia. Amnesic strokes were more often cardioembolic, multiterritorial, and typically involved the posterior circulation and limbic system. Clinical clues were minor focal neurological signs, higher age, more risk factors, and stroke favoring circumstances. Although all patients were independent at 3 months, 31% had persistent memory problems. Amnesia as the main symptom of acute ischemic cerebral events is rare, mostly transient, and easily mistaken for TGA. Although clinical clues are often present, the threshold for performing diffusion-weighted imaging in acute amnesia should be low. © 2017 American Heart Association, Inc.

  18. DRESS and Ischemic Stroke.

    PubMed

    Cahyanur, Rahmat; Oktavia, Dina; Koesno, Sukamto

    2012-07-01

    DRESS (drug rash eosinophilia and systemic symptoms) is a life threatening condition characterized by skin rash, fever, leucocytosis with eosinophilia or atypical lymphocytosis, lymphadenopathy, and internal organ involvement. This case report would like to describe an interesting case of DRESS coincidence with ischemic stroke. A 38 year old woman had been admitted with skin rash and fever since four days before. Four weeks before admission she received antibiotic and multivitamin for one week. The patient looked ill, with body temperature 38.0°C. Marked physical findings were cervical lymphadenopathy and hepatomegaly. Dermatological examination finding was generalized exanthema. Laboratory evaluation showed leucocytosis, eosinophilia, and increased level of ALT and AST. During hospitalization the patient also suffered from ischemic stroke. Treatments administered in this patient were oxygen, adequate intravenous fluid, parenteral nutrition, methyl prednisolone, cethirizin bid, ranitidin bid, and antibiotic. The antibiotic treatment in this case was performed with graded challenge or test dosing.

  19. Adenosine and Ischemic Preconditioning

    PubMed Central

    Liang, Bruce T.; Swierkosz, Tomasz A.; Herrmann, Howard C.; Kimmel, Stephen; Jacobson, Kenneth A.

    2012-01-01

    Adenosine is released in large amounts during myocardial ischemia and is capable of exerting potent cardioprotective effects in the heart. Although these observations on adenosine have been known for a long time, how adenosine acts to achieve its anti-ischemic effect remains incompletely understood. However, recent advances on the chemistry and pharmacology of adenosine receptor ligands have provided important and novel information on the function of adenosine receptor subtypes in the cardiovascular system. The development of model systems for the cardiac actions of adenosine has yielded important insights into its mechanism of action and have begun to elucidate the sequence of signalling events from receptor activation to the actual exertion of its cardioprotective effect. The present review will focus on the adenosine receptors that mediate the potent anti-ischemic effect of adenosine, new ligands at the receptors, potential molecular signalling mechanisms downstream of the receptor, mediators for cardioprotection, and possible clinical applications in cardiovascular disorders. PMID:10607860

  20. Acute ischemic stroke update.

    PubMed

    Baldwin, Kathleen; Orr, Sean; Briand, Mary; Piazza, Carolyn; Veydt, Annita; McCoy, Stacey

    2010-05-01

    Stroke is the third most common cause of death in the United States and is the number one cause of long-term disability. Legislative mandates, largely the result of the American Heart Association, American Stroke Association, and Brain Attack Coalition working cooperatively, have resulted in nationwide standardization of care for patients who experience a stroke. Transport to a skilled facility that can provide optimal care, including immediate treatment to halt or reverse the damage caused by stroke, must occur swiftly. Admission to a certified stroke center is recommended for improving outcomes. Most strokes are ischemic in nature. Acute ischemic stroke is a heterogeneous group of vascular diseases, which makes targeted treatment challenging. To provide a thorough review of the literature since the 2007 acute ischemic stroke guidelines were developed, we performed a search of the MEDLINE database (January 1, 2004-July 1, 2009) for relevant English-language studies. Results (through July 1, 2009) from clinical trials included in the Internet Stroke Center registry were also accessed. Results from several pivotal studies have contributed to our knowledge of stroke. Additional data support the efficacy and safety of intravenous alteplase, the standard of care for acute ischemic stroke since 1995. Due to these study results, the American Stroke Association changed its recommendation to extend the time window for administration of intravenous alteplase from within 3 hours to 4.5 hours of symptom onset; this recommendation enables many more patients to receive the drug. Other findings included clinically useful biomarkers, the role of inflammation and infection, an expanded role for placement of intracranial stents, a reduced role for urgent carotid endarterectomy, alternative treatments for large-vessel disease, identification of nontraditional risk factors, including risk factors for women, and newly published pediatric stroke guidelines. In addition, new devices for

  1. [Ischemic hepatitis. Case report].

    PubMed

    Squella, Freddy; Zapata, Rodrigo

    2003-06-01

    Ischemic hepatitis or shock liver is defined as an extensive hepatocellular necrosis associated with a decrease in hepatic perfusion due to systemic hypotension. Serum aminotransferase levels (ALAT and ASAT) increase rapidly after the ischemic episode and peak within 1 to 3 days to at least 20 times the upper normal limit. After recovery, aminotransferases return to near normal levels in 7-10 days of the initial insult. Histological it is characterized by centrolobular necrosis without inflammation. We report a 47 years old woman with a rheumatic mitral valve disease, atrial fibrillation on anticoagulation and congestive heart failure. She was admitted due to a rapid auricular arrhythmia and secondary severe hypotension. She developed rapidly progressive jaundice (bilirubin up to 8.9 mg/dl) and her aminotransferases (ALAT and ASAT) increased rapidly to levels near 100 times the upper normal limit. Other causes of liver disease were excluded. With hemodynamic support and after heart rate control she improved rapidly within the following 10 days with normalization of liver function tests and complete clinical recovery.

  2. Ischemic stroke and depression.

    PubMed

    Desmond, David W; Remien, Robert H; Moroney, Joan T; Stern, Yaakov; Sano, Mary; Williams, Janet B W

    2003-03-01

    Previous studies of depression after stroke have reported widely variable findings, possibly due to differences between studies in patient characteristics and methods for the assessment of depression, small sample sizes, and the failure to examine stroke-free reference groups to determine the base rate of depression in the general population. In an effort to address certain of those methodologic issues and further investigate the frequency and clinical determinants of depression after stroke, we administered the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D) and neurological, neuropsychological, and functional assessments to 421 patients (age = 71.5 +/- 8.0 years) 3 months after ischemic stroke and 249 stroke-free control subjects (age = 70.8 +/- 6.7 years). We required a SIGH-D total score > 11 for the identification of depression. We found that depression was less frequent (47/421 patients, or 11.2%, and 13/249 control subjects, or 5.2%), less severe, and less persistent in our stroke cohort than previously reported, possibly due to the underrepresentation of patients with a premorbid history of affective illness. Depression was associated with more severe stroke, particularly in vascular territories that supply limbic structures; dementia; and female sex. SIGH-D item analyses suggested that a reliance on nonsomatic rather than somatic symptoms would result in the most accurate diagnoses of depression after ischemic stroke.

  3. Ischemic mitral valve prolapse

    PubMed Central

    Cristiano, Spadaccio; Nenna, Antonio; Chello, Massimo

    2016-01-01

    Ischemic mitral prolapse (IMP) is a pathologic entity encountered in about one-third among the patients undergoing surgery for ischemic mitral regurgitation (IMR). IMP is generally the result of a papillary muscle injury consequent to myocardial, but the recent literature is progressively unveiling a more complex pathogenesis. The mechanisms underlying its development regards the impairment of one or more components of the mitral apparatus, which comprises the annulus, the chordae tendineae, the papillary muscle and the left ventricular wall. IMP is not only a disorder of valvular function, but also entails coexistent aspects of a geometric disturbance of the mitral valve configuration and of the left ventricular function and dimension and a correct understanding of all these aspects is crucial to guide and tailor the correct therapeutic strategy to be adopted. Localization of prolapse, anatomic features of the prolapsed leaflets and the subvalvular apparatus should be carefully evaluated as also constituting the major determinants defining patient’s outcomes. This review will summarize our current understanding of the pathophysiology and clinical evidence on IMP with a particular focus on the surgical treatment. PMID:28149574

  4. Imaging acute ischemic stroke.

    PubMed

    González, R Gilberto; Schwamm, Lee H

    2016-01-01

    Acute ischemic stroke is common and often treatable, but treatment requires reliable information on the state of the brain that may be provided by modern neuroimaging. Critical information includes: the presence of hemorrhage; the site of arterial occlusion; the size of the early infarct "core"; and the size of underperfused, potentially threatened brain parenchyma, commonly referred to as the "penumbra." In this chapter we review the major determinants of outcomes in ischemic stroke patients, and the clinical value of various advanced computed tomography and magnetic resonance imaging methods that may provide key physiologic information in these patients. The focus is on major strokes due to occlusions of large arteries of the anterior circulation, the most common cause of a severe stroke syndrome. The current evidence-based approach to imaging the acute stroke patient at the Massachusetts General Hospital is presented, which is applicable for all stroke types. We conclude with new information on time and stroke evolution that imaging has revealed, and how it may open the possibilities of treating many more patients. © 2016 Elsevier B.V. All rights reserved.

  5. [Cerebrolysin for acute ischemic stroke].

    PubMed

    iganshina, L E; Abakumova, T R

    2013-01-01

    The review discusses existing evidence of benefits and risks of cerebrolysin--a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue with proposed neuroprotective and neurotrophic properties, for acute ischemic stroke. The review presents results of systematic search and analysis of randomised clinical trials comparing cerebrolysin with placebo in patients with acute ischemic stroke. Only one trial was selected as meeting quality criteria. No difference in death and adverse events between cerebrolysin and placebo was established. The authors conclude about insufficiency of evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischemic stroke.

  6. Remote Ischemic Conditioning

    PubMed Central

    Heusch, Gerd; Bøtker, Hans Erik; Przyklenk, Karin; Redington, Andrew; Yellon, Derek

    2014-01-01

    In remote ischemic conditioning (RIC) brief, reversible episodes of ischemia with reperfusion in one vascular bed, tissue or organ confer a global protective phenotype and render remote tissues and organs resistant to ischemia/reperfusion injury. The peripheral stimulus can be chemical, mechanical or electrical and involves activation of peripheral sensory nerves. The signal transfer to the heart or other organs is through neuronal and humoral communications. Protection can be transferred, even across species, with plasma-derived dialysate and involves nitric oxide, stromal derived factor-1α, microRNA-144, but also other, not yet identified factors. Intracardiac signal transduction involves: adenosine, bradykinin, cytokines, and chemokines, which activate specific receptors; intracellular kinases; and mitochondrial function. RIC by repeated brief inflation/deflation of a blood pressure cuff protects against endothelial dysfunction and myocardial injury in percutaneous coronary interventions, coronary artery bypass grafting and reperfused acute myocardial infarction. RIC is safe and effective, noninvasive, easily feasible and inexpensive. PMID:25593060

  7. Preterm Hypoxic–Ischemic Encephalopathy

    PubMed Central

    Gopagondanahalli, Krishna Revanna; Li, Jingang; Fahey, Michael C.; Hunt, Rod W.; Jenkin, Graham; Miller, Suzanne L.; Malhotra, Atul

    2016-01-01

    Hypoxic–ischemic encephalopathy (HIE) is a recognizable and defined clinical syndrome in term infants that results from a severe or prolonged hypoxic–ischemic episode before or during birth. However, in the preterm infant, defining hypoxic–ischemic injury (HII), its clinical course, monitoring, and outcomes remains complex. Few studies examine preterm HIE, and these are heterogeneous, with variable inclusion criteria and outcomes reported. We examine the available evidence that implies that the incidence of hypoxic–ischemic insult in preterm infants is probably higher than recognized and follows a more complex clinical course, with higher rates of adverse neurological outcomes, compared to term infants. This review aims to elucidate the causes and consequences of preterm hypoxia–ischemia, the subsequent clinical encephalopathy syndrome, diagnostic tools, and outcomes. Finally, we suggest a uniform definition for preterm HIE that may help in identifying infants most at risk of adverse outcomes and amenable to neuroprotective therapies. PMID:27812521

  8. Cryoglobulins in Acute Ischemic Stroke

    NASA Astrophysics Data System (ADS)

    Manukyan, L. A.; Ayvazyan, V. A.; Boyajyan, A. S.

    Cryoglobulins (Cgs) are pathogenic immune complexes, non specific markers of the inflammatory and autoimmune responses. In this study we for the first time, revealed Cgs in the blood of ischemic stroke patients and analyze their composition.

  9. Subacute management of ischemic stroke.

    PubMed

    Bernheisel, Christopher R; Schlaudecker, Jeffrey D; Leopold, Katelyn

    2011-12-15

    Ischemic stroke is the third leading cause of death in the United States and a common reason for hospitalization. The subacute period after a stroke refers to the time when the decision to not employ thrombolytics is made up until two weeks after the stroke occurred. Family physicians are often involved in the subacute management of ischemic stroke. All patients with an ischemic stroke should be admitted to the hospital in the subacute period for cardiac and neurologic monitoring. Imaging studies, including magnetic resonance angiography, carotid artery ultrasonography, and/or echocardiography, may be indicated to determine the cause of the stroke. Evaluation for aspiration risk, including a swallowing assessment, should be performed, and nutritional, physical, occupational, and speech therapy should be initiated. Significant causes of morbidity and mortality following ischemic stroke include venous thromboembolism, pressure sores, infection, and delirium, and measures should be taken to prevent these complications. For secondary prevention of future strokes, antiplatelet therapy with aspirin should be initiated within 24 hours of ischemic stroke in all patients without contraindications, and one of several antiplatelet regimens should be continued long-term. Statin therapy should also be given in most situations. Although permissive hypertension is initially warranted, antihypertensive therapy should begin within 24 hours. Diabetes mellitus should be controlled and patients counseled about lifestyle modifications to reduce stroke risk. Rehabilitative therapy following hospitalization improves outcomes and should be considered.

  10. Pathogenic mechanisms following ischemic stroke.

    PubMed

    Khoshnam, Seyed Esmaeil; Winlow, William; Farzaneh, Maryam; Farbood, Yaghoob; Moghaddam, Hadi Fathi

    2017-07-01

    Stroke is the second most common cause of death and the leading cause of disability worldwide. Brain injury following stroke results from a complex series of pathophysiological events including excitotoxicity, oxidative and nitrative stress, inflammation, and apoptosis. Moreover, there is a mechanistic link between brain ischemia, innate and adaptive immune cells, intracranial atherosclerosis, and also the gut microbiota in modifying the cerebral responses to ischemic insult. There are very few treatments for stroke injuries, partly owing to an incomplete understanding of the diverse cellular and molecular changes that occur following ischemic stroke and that are responsible for neuronal death. Experimental discoveries have begun to define the cellular and molecular mechanisms involved in stroke injury, leading to the development of numerous agents that target various injury pathways. In the present article, we review the underlying pathophysiology of ischemic stroke and reveal the intertwined pathways that are promising therapeutic targets.

  11. [Antioxidant therapy in ischemic stroke].

    PubMed

    Suslina, Z A; Federova, T N; Maksimova, M Iu; Riasina, T V; Stvolinskiĭ, S L; Khrapova, E V; Boldyrev, A A

    2000-01-01

    The paper presents the results of investigation of emoxipin, an antioxidant synthetic drug, for treatment of patients with ischemic disorders of cerebral circulation. The drug produced a beneficial clinical effect in patients with lacunar and cardioembolic strokes of moderate severity. Therapy with emoxipin increased endogenic antioxidant activity and improved a clinical status of the patients. The protective effect of carnosine was demonstrated in experimental acute hypobaric hypoxia and cerebral ischemia in rats. The results obtained permit to recommend an inclusion of both emoxipin and carnosine in a combined treatment of ischemic disorders of cerebral circulation.

  12. HYPERTENSIVE-ISCHEMIC LEG ULCERS

    PubMed Central

    Farber, Eugene M.; Schmidt, Otto E. L.

    1950-01-01

    Ischemic ulcers of the leg having characteristics different from those of ordinary leg ulcers have been observed in a small number of hypertensive patients, mostly women, during the past few years. Such ulcers are usually located above the ankle. They begin with a small area of purplish discoloration at the site of slight trauma, and progress to acutely tender ulceration. In studies of tissue removed from the margin and the base of an ulcer of this kind, obliterative arteriolar sclerotic changes, ischemic-appearing connective tissue and inflammatory changes were noted. Two additional cases are reported. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:15398887

  13. [Pregnancy and acute ischemic stroke].

    PubMed

    Bereczki, Dániel

    2016-05-15

    Pregnancy-related ischemic strokes play an important role in both maternal and fetal morbidity and mortality. Changes in hemostaseology and hemodynamics as well as risk factors related to or independent from pregnancy contribute to the increased stroke-risk during gestation and the puerperium. Potential teratogenic effects make diagnostics, acute therapy and prevention challenging. Because randomized, controlled trials are not available, a multicenter registry of patients with gestational stroke would be desirable. Until definite guidelines emerge, management of acute ischemic stroke during pregnancy remains individual, involving experts and weighing the risks and benefits.

  14. Genetic susceptibility to ischemic stroke

    PubMed Central

    Meschia, James F.; Worrall, Bradford B.; Rich, Stephen S.

    2014-01-01

    Clinicians who treat patients with stroke need to be aware of several single-gene disorders that have ischemic stroke as a major feature, including sickle cell disease, Fabry disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and retinal vasculopathy with cerebral leukodystrophy. The reported genome-wide association studies of ischemic stroke and several related phenotypes (for example, ischemic white matter disease) have shown that no single common genetic variant imparts major risk. Larger studies with samples numbering in the thousands are ongoing to identify common variants with smaller effects on risk. Pharmacogenomic studies have uncovered genetic determinants of response to warfarin, statins and clopidogrel. Despite increasing knowledge of stroke genetics, incorporating this new knowledge into clinical practice remains a challenge. The goals of this article are to review common single-gene disorders relevant to ischemic stroke, summarize the status of candidate gene and genome-wide studies aimed at discovering genetic stroke risk factors, and to briefly discuss pharmacogenomics related to stroke treatment. PMID:21629240

  15. Arterial ischemic stroke in HIV

    PubMed Central

    Bryer, Alan; Lucas, Sebastian; Stanley, Alan; Allain, Theresa J.; Joekes, Elizabeth; Emsley, Hedley; Turnbull, Ian; Downey, Colin; Toh, Cheng-Hock; Brown, Kevin; Brown, David; Ison, Catherine; Smith, Colin; Corbett, Elizabeth L.; Nath, Avindra; Heyderman, Robert S.; Connor, Myles D.; Solomon, Tom

    2016-01-01

    HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke. PMID:27386505

  16. Acute Ischemic Stroke Therapy Overview.

    PubMed

    Catanese, Luciana; Tarsia, Joseph; Fisher, Marc

    2017-02-03

    The treatment of acute ischemic stroke has undergone dramatic changes recently subsequent to the demonstrated efficacy of intra-arterial (IA) device-based therapy in multiple trials. The selection of patients for both intravenous and IA therapy is based on timely imaging with either computed tomography or magnetic resonance imaging, and if IA therapy is considered noninvasive, angiography with one of these modalities is necessary to document a large-vessel occlusion amenable for intervention. More advanced computed tomography and magnetic resonance imaging studies are available that can be used to identify a small ischemic core and ischemic penumbra, and this information will contribute increasingly in treatment decisions as the therapeutic time window is lengthened. Intravenous thrombolysis with tissue-type plasminogen activator remains the mainstay of acute stroke therapy within the initial 4.5 hours after stroke onset, despite the lack of Food and Drug Administration approval in the 3- to 4.5-hour time window. In patients with proximal, large-vessel occlusions, IA device-based treatment should be initiated in patients with small/moderate-sized ischemic cores who can be treated within 6 hours of stroke onset. The organization and implementation of regional stroke care systems will be needed to treat as many eligible patients as expeditiously as possible. Novel treatment paradigms can be envisioned combining neuroprotection with IA device treatment to potentially increase the number of patients who can be treated despite long transport times and to ameliorate the consequences of reperfusion injury. Acute stroke treatment has entered a golden age, and many additional advances can be anticipated. © 2017 American Heart Association, Inc.

  17. Renalase protects against ischemic AKI.

    PubMed

    Lee, H Thomas; Kim, Joo Yun; Kim, Mihwa; Wang, Peili; Tang, Lieqi; Baroni, Sara; D'Agati, Vivette D; Desir, Gary V

    2013-02-01

    Elevated levels of plasma catecholamines accompany ischemic AKI, possibly contributing the inflammatory response. Renalase, an amine oxidase secreted by the proximal tubule, degrades circulating catecholamines and reduces myocardial necrosis, suggesting that it may protect against renal ischemia reperfusion injury. Here, mice subjected to renal ischemia reperfusion injury had significantly lower levels of renalase in the plasma and kidney compared with sham-operated mice. Consistent with this, plasma NE levels increased significantly after renal ischemia reperfusion injury. Furthermore, renal tubular inflammation, necrosis, and apoptosis were more severe and plasma catecholamine levels were higher in renalase-deficient mice subjected to renal ischemia reperfusion compared with wild-type mice. Administration of recombinant human renalase reduced plasma catecholamine levels and ameliorated ischemic AKI in wild-type mice. Taken together, these data suggest that renalase protects against ischemic AKI by reducing renal tubular necrosis, apoptosis, and inflammation, and that plasma renalase might be a biomarker for AKI. Recombinant renalase therapy may have potential for the prevention and treatment of AKI.

  18. Treatment of Acute Ischemic Stroke.

    PubMed

    Rabinstein, Alejandro A

    2017-02-01

    This article provides an update on the state of the art of the emergency treatment of acute ischemic stroke with particular emphasis on the alternatives for reperfusion therapy. The results of several randomized controlled trials consistently and conclusively demonstrating that previously functional patients with disabling strokes from a proximal intracranial artery occlusion benefit from prompt recanalization with mechanical thrombectomy using a retrievable stent have changed the landscape of acute stroke therapy. Mechanical thrombectomy within 6 hours of symptom onset should now be considered the preferred treatment for these patients along with IV thrombolysis with recombinant tissue plasminogen activator (rtPA) within the first 4.5 hours for all patients who do not have contraindications for systemic thrombolysis. Patients who are ineligible for IV rtPA can also benefit from mechanical thrombectomy. Collateral status and time to reperfusion are the main determinants of outcome. Timely successful reperfusion is the most effective treatment for patients with acute ischemic stroke. Systems of care should be optimized to maximize the number of patients with acute ischemic stroke able to receive reperfusion therapy.

  19. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.

    PubMed

    Kernan, Walter N; Viscoli, Catherine M; Furie, Karen L; Young, Lawrence H; Inzucchi, Silvio E; Gorman, Mark; Guarino, Peter D; Lovejoy, Anne M; Peduzzi, Peter N; Conwit, Robin; Brass, Lawrence M; Schwartz, Gregory G; Adams, Harold P; Berger, Leo; Carolei, Antonio; Clark, Wayne; Coull, Bruce; Ford, Gary A; Kleindorfer, Dawn; O'Leary, John R; Parsons, Mark W; Ringleb, Peter; Sen, Souvik; Spence, J David; Tanne, David; Wang, David; Winder, Toni R

    2016-04-07

    Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003). In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by

  20. Treatment of Acute Ischemic Stroke.

    PubMed

    Siket, Matthew S

    2016-11-01

    Although stroke declined from the third to fifth most common cause of death in the United States, the annual incidence and overall prevalence continue to increase. Since the available US Food and Drug Administration-approved treatment options are time dependent, improving early stroke care may have more of a public health impact than any other phase of care. Timely and efficient stroke treatment should be a priority for emergency department and prehospital providers. This article discusses currently available and emerging treatment options in acute ischemic stroke focusing on the preservation of salvageable brain tissue, minimizing complications, and secondary prevention. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Neuroprotective Effects of Peptides during Ischemic Preconditioning.

    PubMed

    Zarubina, I V; Shabanov, P D

    2016-02-01

    Experiments on rats showed that neurospecific protein preparations reduce the severity of neurological deficit, restore the structure of individual behavior of the animals with different hypoxia tolerance, and exert antioxidant action during chronic ischemic damage to the brain unfolding during the early and late phases of ischemic preconditioning.

  2. Hyperspectral imaging of ischemic wounds

    NASA Astrophysics Data System (ADS)

    Gnyawali, Surya C.; Elgharably, Haytham; Melvin, James; Huang, Kun; Bergdall, Valerie; Allen, David W.; Hwang, Jeeseong; Litorja, Maritoni; Shirley, Eric; Sen, Chandan K.; Xu, Ronald

    2012-03-01

    Optical imaging has the potential to achieve high spatial resolution and high functional sensitivity in wound assessment. However, clinical acceptance of many optical imaging devices is hampered by poor reproducibility, low accuracy, and lack of biological interpretation. We developed an in vivo model of ischemic flap for non-contact assessment of wound tissue functional parameters and spectral characteristics. The model was created by elevating the bipedicle skin flaps of a domestic pig from the underlying vascular bed and inhibiting graft bed reperfusion by a silastic sheet. Hyperspectral imaging was carried out on the ischemic flap model and compared with transcutaneous oxygen tension and perfusion measurements at different positions of the wound. Hyperspectral images have also been captured continuously during a post-occlusive reactive hyperemia (PORH) procedure. Tissue spectral characteristics obtained by hyperspectral imaging correlated well with cutaneous tissue oxygen tension, blood perfusion, and microscopic changes of tissue morphology. Our experiments not only demonstrated the technical feasibility for quantitative assessment of chronic wound but also provided a potential digital phantom platform for quantitative characterization and calibration of medical optical devices.

  3. Erythropoietin: Powerful Protection of Ischemic and Post-Ischemic Brain

    PubMed Central

    Nguyen, Anh Q.; Cherry, Brandon H.; Scott, Gary F.; Ryou, Myoung-Gwi; Mallet, Robert T.

    2015-01-01

    Ischemic brain injury inflicted by stroke and cardiac arrest ranks among the leading causes of death and long-term disability in the United States. The brain consumes large amounts of metabolic substrates and oxygen to sustain its energy requirements. Consequently, the brain is exquisitely sensitive to interruptions in its blood supply, and suffers irreversible damage after 10–15 minutes of severe ischemia. Effective treatments to protect the brain from stroke and cardiac arrest have proven elusive, due to the complexities of the injury cascades ignited by ischemia and reperfusion. Although recombinant tissue plasminogen activator and therapeutic hypothermia have proven efficacious for stroke and cardiac arrest, respectively, these treatments are constrained by narrow therapeutic windows, potentially detrimental side effects and the limited availability of hypothermia equipment. Mounting evidence demonstrates the cytokine hormone erythropoietin (EPO) to be a powerful neuroprotective agent and a potential adjuvant to established therapies. Classically, EPO originating primarily in the kidneys promotes erythrocyte production by suppressing apoptosis of proerythroid progenitors in bone marrow. However, the brain is capable of producing EPO, and EPO’s membrane receptors and signaling components also are expressed in neurons and astrocytes. EPO activates signaling cascades that increase the brain’s resistance to ischemia-reperfusion stress by stabilizing mitochondrial membranes, limiting formation of reactive oxygen and nitrogen intermediates, and suppressing pro-inflammatory cytokine production and neutrophil infiltration. Collectively, these mechanisms preserve functional brain tissue and, thus, improve neurocognitive recovery from brain ischemia. This article reviews the mechanisms mediating EPO-induced brain protection, critiques the clinical utility of exogenous EPO to preserve brain threatened by ischemic stroke and cardiac arrest, and discusses the

  4. Nascent proteomes of ischemic-injured and ischemic-tolerant neuronal cells

    PubMed Central

    Zhou, An; Simon, Roger P.; David, Larry

    2011-01-01

    In a recent study on ischemic rodent brains, we quantitatively characterised and compared brain proteomes under ischemic-preconditioned or injured or tolerant conditions. We discovered an enriched presence of repressive transcriptional regulator proteins with essential roles as epigenetic regulators in ischemic-tolerant brains (Stapels et al., 2010). We further showed their robust, dynamic and differential changes under different ischemic conditions in brains and in cultured neuronal cells. In the present work, using neuronal cell cultures, we aimed to characterise the nascent proteome, the proteome that presents early when the cells receive an ischemic insult. These would be the proteomic changes of newly synthesised proteins. Identification of effectors of this phase of response to ischemia bears the best promise of identifying therapeutic targets for treating acute stroke when patients present to hospital. We compared these nascent proteomes across different ischemic conditions using bioinformatic tools. PMID:21330693

  5. Nonarteritic anterior ischemic optic neuropathy.

    PubMed

    Atkins, Edward J

    2011-02-01

    Currently there is no generally accepted, well-proven treatment for nonarteritic anterior ischemic optic neuropathy (NAION). Most proposed treatments are empirical and include antithrombotics, vasodynamic agents, treatments aimed at reducing optic disc edema, and various neuroprotective strategies. Most potential treatments have been inadequately studied, prematurely embraced, or prematurely discarded. Evidence for antithrombotic agents is lacking, and small vessel arterial occlusion has never been demonstrated in NAION. Antiplatelet agents have not been studied in acute NAION, but they are often prescribed for acute treatment because of their proven role in stroke prevention. Because NAION is an ischemic disorder occurring more often after the age of 50 in patients with vascular risk factors, I recommend aggressive risk-factor management and antiplatelet therapy. The evidence that aspirin can help to prevent NAION in the fellow eye is divided. I recommend aspirin for secondary prevention, mostly for its proven role in stroke prevention. NAION occurs in patients with physiologically crowded optic nerves and small cup-to-disc ratios. Disc edema may contribute to a "compartment syndrome," which compresses the fine capillary blood supply of the optic nerve head, resulting in ischemia and axonal damage. There is some limited and debatable evidence that oral steroids may shorten the duration of disc edema and improve visual outcome in NAION. I discuss this evidence with patients who present acutely with NAION, and although I consider prescribing oral steroids on a case-by-case basis, I will not routinely recommend oral steroids until a properly randomized clinical trial is performed. Some neuroprotective strategies have been studied, but none have proven to be helpful. Although some (eg, brimonidine) are probably not harmful, I do not recommend these treatments. Early referral to low vision services may help to improve functional visual outcome.

  6. Ischemic Stroke After Wasp Sting.

    PubMed

    Kulhari, Ashish; Rogers, Ashley; Wang, Han; Kumaraswamy, Vishakhadatta Mathur; Xiong, Wei; DeGeorgia, Michael

    2016-10-01

    Despite the common occurrence of hymenopteran stings worldwide, primary neurologic manifestations including stroke are rare. We report a case of a healthy male who developed a right middle cerebral artery (MCA) territory ischemic stroke after getting stung by a wasp. A 44-year-old man with hypertension presented to the hospital with sudden-onset left hemiparesis, left facial weakness, and dysarthria after being stung by a wasp. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) scans of the brain revealed a right MCA territory infarct and a lack of flow in the distal right internal carotid artery and MCA. He was treated with intravenous tissue plasminogen activator. A computed tomography angiography scan of the brain performed 24 hours later revealed multiple regions of vasoconstriction in the territory of the bilateral MCA. Evaluations for causes of stroke, including echocardiography and telemetry, were not revealing. Immunologic testing showed significantly elevated levels of serum wasp immunoglobulin E. Therapy with aspirin and atorvastatin was started. At discharge, the patient had a mild left facial droop but normal strength in his left arm and leg. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians encounter large numbers of hymenopteran sting cases each year. These patients typically present with local reactions, such as itching, pain, and erythema. Systemic manifestations, such as anaphylaxis causing severe hypotension and bronchospasm, are less common but deadly. Neurologic complications, such as ischemic stroke, are extremely rare. This manuscript highlights the pathophysiology and management of stroke after a hymenopteran sting. There are no guidelines for the management of stroke after a hymenopteran sting, and therefore we intend to provide some guidance to physicians for treating stroke after a hymenopteran sting. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. [Antiphospholipid antibodies and ischemic heart disease].

    PubMed

    Jørgensen, P; Hansen, P R

    1991-08-05

    A case is presented with severe ischemic heart disease and lupus anticoagulant in a 24 year old otherwise healthy male. Anticoagulation was initiated and coronary by-pass grafting was performed. Coronary biopsy showed no signs of arteritis.

  8. Histopathologic studies of ischemic optic neuropathy.

    PubMed Central

    Knox, D L; Kerrison, J B; Green, W R

    2000-01-01

    PURPOSE: To define the histopathologic features of eyes in which a pathologic diagnosis of ischemic optic neuropathy had been made in the years 1951 through 1998. METHODS: The following data were documented: age of patient, race, sex, source of tissue, cause of death, clinical history, interval from loss of vision to death, enucleation, exenteration, and biopsy. The histopathologic criteria for diagnosis of ischemic optic neuropathy were the presence of localized ischemic edema, cavernous degeneration, or an area of atrophy located superior or inferior in the optic nerve. Cases with history of abrupt loss of vision were combined with reports from the literature to construct a time table of histopathologic features and associated conditions. RESULTS: Ischemic optic neuropathy was present in 193 eyes. There were 88 females and 65 males. The average age was 71.6 years. Ischemic edema without (early) and with (later) gitter macrophages was present in 26 (13.5%). Cavernous degeneration was present in 69 nerves (36%). Mucopolysaccharide (MPS) was present in 37 cavernous lesions 1 month or longer after loss of vision. Cavernous lesions were seen in 3 eyes in which peripapillary retinal nerve fiber layer hemorrhage had been observed prior to death. Atrophic lesions, the most common pattern, were observed in 133 optic nerves (66.8%). More than 1 ischemic lesion was seen in 38 optic nerves (19.7%). Bilateral ischemic lesions were seen in 50 (35.2%) of 142 paired eyes. CONCLUSIONS: Ischemic optic nerve lesions are initially acellular and later show macrophage infiltration. Cavernous lesions with MPS are present 4 weeks or longer after vision loss. The location of MPS posteriorly and along the internal margin suggests that MPS is produced at the edges of lesions. Progressive vision loss in ischemic optic neuropathy may be secondary to compression of intact nerve from ischemic edema and cavernous swelling, or a second ischemic lesion. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5

  9. Case report: MRI of decubital ischemic fasciitis

    PubMed Central

    Ulus, Ozden Sila; Karaarslan, Ercan; Saglican, Yesim; Yakupoglu, Abdullah

    2011-01-01

    The MRI findings in a case of decubital ischemic fasciitis located posterolateral to the right greater trochanter, in a 72-year-old woman, are presented. Decubital ischemic fasciitis is an uncommon entity encountered mostly in debilitated, elderly patients, in the deep subcutaneous tissue, at pressure points or bony prominences. It can simulate soft-tissue sarcomas. Recognition of this lesion radiologically is important to prevent unnecessary interventions. PMID:21799593

  10. [Stunned myocardium after acute ischemic stroke].

    PubMed

    Varela, Daniel; Díaz, Fernanda; Hlavnicka, Alejandro; Wainsztein, Néstor; Leiguarda, Ramón

    2006-01-01

    The so-called stunned myocardium, defined as transitory myocardial contractile dysfunction, has been clearly demonstrated in diverse clinical situations. However, stunned myocardium related to ischemic stroke has been poorly identified. We describe two patients with diagnosis of acute ischemic stroke who developed eletrocardiographic changes, cardiac enzyme increasing levels and myocardial dysfunction secondary to abnormal cardiac wall motion. At the same time the patients developed acute lung injury with rapid resolution, perhaps as a consequence of neurocardiogenic components.

  11. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

    Yan, Lin; Kudej, Raymond K; Vatner, Dorothy E; Vatner, Stephen F

    2015-03-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation.

  12. Ischemic brain injury in cerebral amyloid angiopathy

    PubMed Central

    van Veluw, Susanne J; Greenberg, Steven M

    2016-01-01

    Cerebral amyloid angiopathy (CAA) is a common form of cerebral small vessel disease and an important risk factor for intracerebral hemorrhage and cognitive impairment. While the majority of research has focused on the hemorrhagic manifestation of CAA, its ischemic manifestations appear to have substantial clinical relevance as well. Findings from imaging and pathologic studies indicate that ischemic lesions are common in CAA, including white-matter hyperintensities, microinfarcts, and microstructural tissue abnormalities as detected with diffusion tensor imaging. Furthermore, imaging markers of ischemic disease show a robust association with cognition, independent of age, hemorrhagic lesions, and traditional vascular risk factors. Widespread ischemic tissue injury may affect cognition by disrupting white-matter connectivity, thereby hampering communication between brain regions. Challenges are to identify imaging markers that are able to capture widespread microvascular lesion burden in vivo and to further unravel the etiology of ischemic tissue injury by linking structural magnetic resonance imaging (MRI) abnormalities to their underlying pathophysiology and histopathology. A better understanding of the underlying mechanisms of ischemic brain injury in CAA will be a key step toward new interventions to improve long-term cognitive outcomes for patients with CAA. PMID:25944592

  13. Myocardial ischemic protection in natural mammalian hibernation

    PubMed Central

    Yan, Lin; Kudej, Raymond K.; Vatner, Dorothy E.

    2015-01-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  14. [Ocular ischemic syndrome--a case report].

    PubMed

    Zemba, M; Avram, Corina Ioana; Ochinciuc, Uliana; Stamate, Alina Cristina; Camburu, Raluca Lăcrămioara

    2013-01-01

    Ocular ischemic syndrome, also known as hypoperfusion/ hypotensive retinopathy or as ischemic oculopathy is a rare ocular disease determined by chronic arterial hypoperfusion through central retinal artery, posterior and anterior ciliary arteries. It is bilateral in 20% of the cases. Most often it appears due to severe occlusion of the carotid arteries (ICA, MCA>ECA), described in 1963 by Kearns and Hollenhorst. Occasionally it can be determined by the obstruction of ophtalmic artery or some arterities (Takayasu, giant cell arteritis). The risk factors are: age between 50-80 years, males (M:F = 2:1), arterial hypertension, diabetes, coronary diseases (5% of the cases develop ocular ischemic syndrome), vascular stroke, hemodialysis. The case we present is of an 63 years old man known with primary arterial hypertension, hypercholesterolemia, diabetes type 2 non insulin dependent and diagnosticated with ischemic cerebral stroke and bilateral obstruction of internal carotid arteries in march 2010, who is presenting for visual impairment in both eyes. The imaging investigations show important carotid occlusion and at the ophthalmologic evaluation there are ocular hypertension and rubeosis iridis at the right eye, optic atrophy at both eyes (complete in the right eye and partial in the left eye), with superior altitudinal visual field defect in left eye. The following diagnosis was established: Chronic ocular ischemic syndrome in both eyes with Neovascular glaucoma at the right eye, Anterior ischemic optic neuropathy at the left eye and laser panphotocoagulation at the right eye was started.

  15. Thrombolytic therapy for acute ischemic stroke after recent transient ischemic attack.

    PubMed

    Alonso de Leciñana, María; Fuentes, Blanca; Masjuan, Jaime; Simal, Patricia; Díaz-Otero, Fernando; Reig, Gemma; Díez-Tejedor, Exuperio; Gil-Nuñez, Antonio; Vivancos, Jose; Egido, Jose-Antonio

    2012-04-01

    Safety and efficacy of intravenous thrombolysis in stroke patients with recent transient ischemic attack are hotly debated. Patients suffering transient ischemic attack may present with diffusion-weighted imaging lesions, and although normal computed tomography would not preclude thrombolysis, the concern is that they may be at higher risk for hemorrhage post-thrombolysis treatment. Prior ipsilateral transient ischemic attack might provide protection due to ischemic preconditioning. We assessed post-thrombolysis outcomes in stroke patients who had prior transient ischemic attack. Multicentered prospective study of consecutive acute stroke patients treated with intravenous tissue plasminogen activator (tPA). Ipsilateral transient ischemic attack, baseline characteristics, risk factors, etiology, and time-lapse to treatment were recorded. National Institutes of Health Stroke Scale at seven-days and modified Rankin Scale at three-months, symptomatic intracranial hemorrhage, and mortality were compared in patients with and without transient ischemic attack. There were 877 patients included, 60 (6·84%) had previous ipsilateral transient ischemic attack within one-month prior to the current stroke (65% in the previous 24 h). Transient ischemic attack patients were more frequently men (70% vs. 53%; P = 0·011), younger (63 vs. 71 years of age; P = 0·011), smokers (37% vs. 25%; P = 0·043), and with large vessel disease (40% vs. 25%; P = 0·011). Severity of stroke at onset was similar to those with and without prior transient ischemic attack (median National Institutes of Health Stroke Scale score 12 vs. 14 P = 0·134). Those with previous transient ischemic attack were treated earlier (117 ± 52 vs. 144 ± 38 mins; P < 0·005). After adjustment for confounding variables, regression analysis showed that previous transient ischemic attack was not associated with differences in stroke outcome such as independence (modified Rankin Scale 0

  16. Radionuclide imaging in ischemic stroke.

    PubMed

    Heiss, Wolf-Dieter

    2014-11-01

    Ischemic stroke is caused by interruption or significant impairment of blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphologic damage. The changes in regional cerebral blood flow and regional metabolism can be assessed by radionuclide imaging, especially SPECT and PET. SPECT and PET have broadened our understanding of flow and metabolic thresholds critical for maintenance of brain function and morphology: PET was essential in the transfer of the concept of the penumbra to clinical stroke and thereby had a great impact on developing treatment strategies. Receptor ligands can be applied as early markers of irreversible neuronal damage and can predict the size of the final infarcts, which is important for decisions on invasive therapy in large ("malignant") infarction. With SPECT and PET, the reserve capacity of the blood supply can be tested in obstructive arteriosclerosis, which is essential for planning interventions. The effect of a stroke on surrounding and contralateral primarily unaffected tissue can be investigated, helping to understand symptoms caused by disturbance in functional networks. Activation studies are useful to demonstrate alternative pathways to compensate for lesions and to test the effect of rehabilitative therapy. Radioisotope studies help to detect neuroinflammation and its effect on extension of tissue damage. Despite the limitations of broad clinical application of radionuclide imaging, this technology has a great impact on research in cerebrovascular diseases and still has various applications in the management of stroke. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  17. Study of retinal vessel oxygen saturation in ischemic and non-ischemic branch retinal vein occlusion

    PubMed Central

    Lin, Lei-Lei; Dong, Yan-Min; Zong, Yao; Zheng, Qi-Shan; Fu, Yue; Yuan, Yong-Guang; Huang, Xia; Qian, Garrett; Gao, Qian-Ying

    2016-01-01

    AIM To explore how oxygen saturation in retinal blood vessels is altered in ischemic and non-ischemic branch retinal vein occlusion (BRVO). METHODS Fifty BRVO eyes were divided into ischemic (n=26) and non-ischemic (n=24) groups, based on fundus fluorescein angiography. Healthy individuals (n=52 and n=48, respectively) were also recruited as controls for the two groups. The mean oxygen saturations of the occluded vessels and central vessels were measured by oximetry in the BRVO and control groups. RESULTS In the ischemic BRVO group, the occluded arterioles oxygen saturation (SaO2-A, 106.0%±14.3%), instead of the occluded venule oxygen saturation (SaO2-V, 60.8%±9.4%), showed increases when compared with those in the same quadrant vessels (SaO2-A, 86.1%±16.5%) in the contralateral eyes (P<0.05). The oxygen saturations of the central vessels showed similar trends with those of the occluded vessels. In the non-ischemic BRVO group, the occluded and central SaO2-V and SaO2-A showed no significant changes. In both the ischemic and non-ischemic BRVOs, the central SaO2-A was significantly increased when compared to healthy individuals. CONCLUSION Obvious changes in the occluded and central SaO2-A were found in the ischemic BRVO group, indicating that disorders of oxygen metabolism in the arterioles may participate in the pathogenesis of ischemic BRVO. PMID:26949618

  18. Acute antithrombotic treatment of ischemic stroke.

    PubMed

    Alderazi, Yazan J; Grotta, James C

    2014-05-01

    Antithrombotic medication is a cornerstone of acute ischemic stroke treatment and secondary prevention. The efficacy of thrombolysis with alteplase in acute stroke has been demonstrated in several clinical trials. This safe and costeffective therapy has transformed the practice of stroke care and has led to subsequent trials of other antithrombotic medications for treatment of ischemic stroke in the acute phase. These antithrombotics include thrombolytic, antiplatelet and anticoagulant agents. While, no other medication has yet demonstrated adequate efficacy, our current and evolving understanding of infarct expansion, ischemic penumbra, collateral circulation and the blood brain barrier is allowing testing of antithrombotic medications tailored to individual patient pathophysiology in clinical trials. This understanding accompanies developments in neuroimaging and organization of stroke care that allow for wide-spread recruitment in these trials. Alteplase remains the mainstay treatment of arterial acute ischemic stroke; however, anticoagulation is the standard therapy for cerebral venous sinus thrombosis. Antithrombotic use in acute stroke, arterial and venous, has demonstrated efficacy but leaves many questions unanswered. This patient population is a fertile ground for novel research, especially as it relates to; combination antithrombotic therapy, combination of pharmacological and mechanical thrombolysis, and the transition to secondary prevention. Here we review the current antithrombotics in the acute phase of ischemic stroke highlighting the evidence-base and areas of uncertainty.

  19. Critical care in acute ischemic stroke.

    PubMed

    McDermott, M; Jacobs, T; Morgenstern, L

    2017-01-01

    Most ischemic strokes are managed on the ward or on designated stroke units. A significant proportion of patients with ischemic stroke require more specialized care. Several studies have shown improved outcomes for patients with acute ischemic stroke when neurocritical care services are available. Features of acute ischemic stroke patients requiring intensive care unit-level care include airway or respiratory compromise; large cerebral or cerebellar hemisphere infarction with swelling; infarction with symptomatic hemorrhagic transformation; infarction complicated by seizures; and a large proportion of patients require close management of blood pressure after thrombolytics. In this chapter, we discuss aspects of acute ischemic stroke care that are of particular relevance to a neurointensivist, covering neuropathology, neurodiagnostics and imaging, blood pressure management, glycemic control, temperature management, and the selection and timing of antithrombotics. We also focus on the care of patients who have received intravenous thrombolysis or mechanical thrombectomy. Complex clinical decision making in decompressive hemicraniectomy for hemispheric infarction and urgent management of basilar artery thrombosis are specifically addressed. © 2017 Elsevier B.V. All rights reserved.

  20. Genetic Predisposition to Ischemic Stroke

    PubMed Central

    Kamatani, Yoichiro; Takahashi, Atsushi; Hata, Jun; Furukawa, Ryohei; Shiwa, Yuh; Yamaji, Taiki; Hara, Megumi; Tanno, Kozo; Ohmomo, Hideki; Ono, Kanako; Takashima, Naoyuki; Matsuda, Koichi; Wakai, Kenji; Sawada, Norie; Iwasaki, Motoki; Yamagishi, Kazumasa; Ago, Tetsuro; Ninomiya, Toshiharu; Fukushima, Akimune; Hozawa, Atsushi; Minegishi, Naoko; Satoh, Mamoru; Endo, Ryujin; Sasaki, Makoto; Sakata, Kiyomi; Kobayashi, Seiichiro; Ogasawara, Kuniaki; Nakamura, Motoyuki; Hitomi, Jiro; Kita, Yoshikuni; Tanaka, Keitaro; Iso, Hiroyasu; Kitazono, Takanari; Kubo, Michiaki; Tanaka, Hideo; Tsugane, Shoichiro; Kiyohara, Yutaka; Yamamoto, Masayuki; Sobue, Kenji; Shimizu, Atsushi

    2017-01-01

    Background and Purpose— The prediction of genetic predispositions to ischemic stroke (IS) may allow the identification of individuals at elevated risk and thereby prevent IS in clinical practice. Previously developed weighted multilocus genetic risk scores showed limited predictive ability for IS. Here, we investigated the predictive ability of a newer method, polygenic risk score (polyGRS), based on the idea that a few strong signals, as well as several weaker signals, can be collectively informative to determine IS risk. Methods— We genotyped 13 214 Japanese individuals with IS and 26 470 controls (derivation samples) and generated both multilocus genetic risk scores and polyGRS, using the same derivation data set. The predictive abilities of each scoring system were then assessed using 2 independent sets of Japanese samples (KyushuU and JPJM data sets). Results— In both validation data sets, polyGRS was shown to be significantly associated with IS, but weighted multilocus genetic risk scores was not. Comparing the highest with the lowest polyGRS quintile, the odds ratios for IS were 1.75 (95% confidence interval, 1.33–2.31) and 1.99 (95% confidence interval, 1.19–3.33) in the KyushuU and JPJM samples, respectively. Using the KyushuU samples, the addition of polyGRS to a nongenetic risk model resulted in a significant improvement of the predictive ability (net reclassification improvement=0.151; P<0.001). Conclusions— The polyGRS was shown to be superior to weighted multilocus genetic risk scores as an IS prediction model. Thus, together with the nongenetic risk factors, polyGRS will provide valuable information for individual risk assessment and management of modifiable risk factors. PMID:28034966

  1. Copeptin and risk stratification in patients with ischemic stroke and transient ischemic attack: the CoRisk study.

    PubMed

    De Marchis, Gian Marco; Katan, Mira; Weck, Anja; Brekenfeld, Caspar; Mattle, Heinrich P; Buhl, Daniela; Müller, Beat; Christ-Crain, Mirjam; Arnold, Marcel

    2013-04-01

    Copeptin independently predicts functional outcome and mortality at 90 days and one-year after ischemic stroke. In patients with transient ischemic attack, elevated copeptin values indicate an increased risk of further cerebrovascular events. The Copeptin Risk Stratification (CoRisk) study aims to validate the predictive value of copeptin in patients with ischemic stroke and transient ischemic attack. In patients with ischemic stroke, the CoRisk study aims to further explore the effect of treatment (i.e. thrombolysis) on the predictive value of copeptin. Prospective observational multicenter study analyzing three groups of patients, i.e. patients with ischemic stroke treated with and without thrombolysis and patients with transient ischemic attack. Primary end-point: In patients with ischemic stroke, the primary end-point includes disability (modified Rankin scale from 3 to 5) and mortality (modified Rankin scale 6) at three-months after stroke. In patients with transient ischemic attack, the primary end-point is a recurrent ischemic cerebrovascular event (i.e. ischemic stroke or recurrent transient ischemic attack). Secondary end-point: In patients with ischemic stroke, the secondary end-points include in-house complications (i.e. symptomatic intracerebral hemorrhage, malignant edema, aspiration pneumonia or seizures during hospitalization, and in-house mortality). © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

  2. Dual antiplatelet therapy after noncardioembolic ischemic stroke or transient ischemic attack: pros and cons.

    PubMed

    Hong, Keun-Sik

    2014-07-01

    Dual antiplatelet therapy simultaneously blocks different platelet activation pathways and might thus be more potent at inhibiting platelet activation and more effective at reducing major ischemic vascular events compared to antiplatelet monotherapy. Aspirin plus clopidogrel dual therapy is now the standard therapy for patients with acute coronary syndrome and for those undergoing percutaneous coronary intervention. However, dual antiplatelet therapy carries an increased risk of bleeding. Patients with ischemic stroke or transient ischemic attack (TIA) are generally older and likely to have a fragile cerebrovascular bed, which further increases the risk of systemic major bleeding events and intracranial hemorrhage. Clinical trials and meta-analyses suggest that in comparison to antiplatelet monotherapy, dual antiplatelet therapy initiated early after noncardioembolic ischemic stroke or TIA further reduces the rate of recurrent stroke and major vascular events without significantly increasing the rate of major bleeding events. In contrast, studies of long-term therapy in patients with noncardioembolic ischemic stroke or TIA have yielded inconsistent data regarding the benefit of dual antiplatelet therapy over monotherapy. However, the harm associated with major bleeding events, including intracranial hemorrhage, which is generally more disabling and more fatal than ischemic stroke, is likely to increase with dual antiplatelet therapy. Physicians should carefully assess the benefits and risks of dual antiplatelet therapy versus antiplatelet monotherapy when managing patients with ischemic stroke or TIA.

  3. [Secondary prevention of ischemic stroke in children].

    PubMed

    Zykov, V P; Komarova, I B

    2012-01-01

    Pediatric arterial ischemic stroke (IS) is an important cause of lifelong disability. Arteriopathies due to trauma and infection are an important underlying cause of childhood arterial ischemic stroke. The secondary prevention of IS should be conducted taking into account the main pathogenetic mechanisms and vascular risk factors. For secondary stroke prevention, the majority of children are treated with either anticoagulation or antiplatelet therapies. This review focuses on the recent international clinical recommendations in secondary stroke prevention based on the results of randomized multicenter clinical studies published by the USA. cardiology association. Experience of anticoagulation or antiplatelet therapies for secondary stroke prevention is insufficient in Russia. Taking into account the available international recommendations is expedient for creation and practical application of the Russian standards for secondary arterial ischemic stroke prevention.

  4. Mitral valve repair for ischemic mitral regurgitation.

    PubMed

    Mohebali, Jahan; Chen, Frederick Y

    2015-05-01

    Mitral valve repair for ischemic mitral valve regurgitation remains controversial. In moderate mitral regurgitation (MR), controversy exists whether revascularization alone will be adequate to restore native valve geometry or whether intervention on the valve (repair) should be performed concomitantly. When MR is severe, the need for valve intervention is not disputed. Rather, the controversy is whether repair versus replacement should be undertaken. In contrast to degenerative or myxomatous disease that directly affects leaflet integrity and morphology, ischemic FMR results from a distortion and dilation of native ventricular geometry that normally supports normal leaflet coaptation. To address this, the first and most crucial step in successful valve repair is placement of an undersized, complete remodeling annuloplasty ring to restore the annulus to its native geometry. The following article outlines the steps for repair of ischemic mitral regurgitation.

  5. Resilience in Patients with Ischemic Heart Disease

    PubMed Central

    de Lemos, Conceição Maria Martins; Moraes, David William; Pellanda, Lucia Campos

    2016-01-01

    Background Resilience is a psychosocial factor associated with clinical outcomes in chronic diseases. The relationship between this protective factor and certain diseases, such heart diseases, is still under-explored. Objective The present study sought to investigate the frequency of resilience in individuals with ischemic heart disease. Method This was a cross-sectional study with 133 patients of both genders, aged between 35 and 65 years, treated at Rio Grande do Sul Cardiology Institute - Cardiology University Foundation, with a diagnosis of ischemic heart disease during the study period. Sixty-seven patients had a history of acute myocardial infarction. The individuals were interviewed and evaluated by the Wagnild & Young resilience scale and a sociodemographic questionnaire. Results Eighty-one percent of patients were classified as resilient according to the scale. Conclusion In the sample studied, resilience was identified in high proportion among patients with ischemic heart disease. PMID:26815312

  6. Spectroscopic monitoring of kidney tissue ischemic injury

    NASA Astrophysics Data System (ADS)

    Fitzgerald, Jason T.; Michalopoulou, Andromachi P.; Troppmann, Christoph; Demos, Stavros G.

    2004-07-01

    Noninvasive evaluation of tissue viability of donor kidneys used for transplantation is an issue that current technology is not able to address. In this work, we explore optical spectroscopy for its potential to assess the degree of ischemic damage in kidney tissue. We hypothesized that ischemic damage to kidney tissue will give rise to changes in its optical properties which in turn may be used to asses the degree of tissue injury. The experimental results demonstrate that the autofluorescence intensity of the injured kidney is decreasing as a function of time exposed to ischemic injury. Changes were also observed in the NIR light scattering intensities most probably arising from changes due to injury and death of the tissue.

  7. Spectroscopic Monitoring of Kidney Tissue Ischemic Injury

    SciTech Connect

    Demos, S G; Fitzgerald, J T; Michalopoulou, A P; Troppmann, C

    2004-03-11

    Noninvasive evaluation of tissue viability of donor kidneys used for transplantation is an issue that current technology is not able to address. In this work, we explore optical spectroscopy for its potential to assess the degree of ischemic damage in kidney tissue. We hypothesized that ischemic damage to kidney tissue will give rise to changes in its optical properties which in turn may be used to asses the degree of tissue injury. The experimental results demonstrate that the autofluorescence intensity of the injured kidney is decreasing as a function of time exposed to ischemic injury. Changes were also observed in the NIR light scattering intensities most probably arising from changes due to injury and death of the tissue.

  8. Cardiac magnetic resonance determinants of functional mitral regurgitation in ischemic and non ischemic left ventricular dysfunction.

    PubMed

    Fernández-Golfín, Covadonga; De Agustin, Alberto; Manzano, M Carmen; Bustos, Ana; Sánchez, Tibisay; Pérez de Isla, Leopoldo; Fuentes, Manuel; Macaya, Carlos; Zamorano, José

    2011-04-01

    Functional mitral regurgitation (FMR) is frequent in left ventricular (LV) dilatation/dysfunction. Echocardiographic predictors of FMR are known. However, cardiac magnetic resonance (CMR) predictors of FMR have not been fully addressed. The aim of the study was to evaluate CMR mitral valve (MV) parameters associated with FMR in ischemic and non ischemic LV dysfunction. 80 patients with LV ejection fraction below 45% and/or left ventricular dilatation of ischemic and non ischemic etiology were included. Cine-MR images (steady state free-precession) were acquired in a short-axis and 4 chambers views where MV evaluation was performed. Delayed enhancement was performed as well. Significant FMR was established as more than mild MR according to the echocardiographic report. Mean age was 59 years, males 79%. FMR was detected in 20 patients (25%) Significant differences were noted in LV functional parameters and in most MV parameters according to the presence of significant FMR. However, differences were noted between ischemic and non ischemic groups. In the first, differences in most MV parameters remained significant while in the non ischemic, only systolic and diastolic interpapillary muscle distance (1.60 vs. 2.19 cm, P = 0.001; 2. 51 vs. 3.04, P = 0.008) were predictors of FMR. FMR is associated with a more severe LV dilatation/dysfunction in the overall population. CMR MV parameters are associated with the presence of significant FMR and are different between ischemic and non ischemic patients. CMR evaluation of these patients may help in risk stratification as well as in surgical candidate selection.

  9. Drug Delivery to the Ischemic Brain

    PubMed Central

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

  10. [Transient ischemic attack: past, present, and future].

    PubMed

    Sato, Shoichiro; Minematsu, Kazuo

    2013-07-01

    Transient ischemic attack (TIA) is a brief episode of reversible neurological deficits caused by focal and temporary central nervous system ischemia. TIA is associated with a high risk of recurrent ischemic stroke, but immediate evaluation and intervention for TIA lowers this risk of recurrent ischemic stroke. A new clinical concept termed acute cerebrovascular syndrome (ACVS) that includes TIA and acute ischemic stroke has been proposed. With the development of new neuroimaging modalities such as diffusion-weighted image (DWI), the definition of TIA used in the United States has shifted from time-based (less than 24 h) to tissue-based (without acute infarction). High ABCD2 score, carotid artery stenosis, and DWI lesions suggest that patients are at a high risk for early recurrence of ischemic stroke. Recently, it was reported that not only DWI or magnetic resonance angiography(MRA), but also fluid-attenuated inversion recovery (FLAIR) images are useful for evaluating TIA. In Japan, the definition of TIA has not been revised since 1990. To review the definition of TIA and establish a TIA management system that is suitable to domestic healthcare environment, the Japan TIA research group (PI, Kazuo Minematsu) was formed in 2009. The group conducted a nation-wide survey and a retrospective registration study to clarify the current status of clinical practice of TIA. In the group's opinion, TIA is defined as the presence of focal neurological symptoms ascribable to a vascular etiology lasting less than 24 h, irrespective of imaging findings, as classically defined. However, if acute ischemic lesions are found on DWI, it is diagnosed as "TIA with DWI lesions." The group also made recommendations for hospitalization policies and outpatient management.

  11. Bacterial pneumonia following acute ischemic stroke.

    PubMed

    Chen, Li-Fu; Chang, Cheng-Yu; Hsu, Li-Cho; Tsai, Ping-Huang; Chang, Shu-Ju; Chang, Shih-Chieh; Yuan, Mei-Kang; Lai, Yi-Chun; Liu, Yu-Chang; Wang, Wei-Shu

    2013-02-01

    The most common serious complication following acute ischemic stroke is pneumonia, which may increase mortality and worsen clinical outcomes. The purpose of this study was to investigate the predictors of 30-day mortality in patients with pneumonia following acute ischemic stroke. From June 2006 to May 2011, we retrospectively included 51 patients with pneumonia following acute ischemic stroke. We analyzed the clinical features, microbiologic data, and outcomes. Predictors of 30-day mortality were investigated by univariate and multivariate analysis. The acute ischemic strokes were caused by large-artery atherosclerosis in 37 (72.5%) of the 51 patients. We found that the most common pathogen responsible for poststroke pneumonia was Klebsiella pneumoniae, followed by Pseudomonas aeruginosa and Escherichia coli. Ultimately, 12 patients died of progressive sepsis due to pneumonia after the acute ischemic stroke. The 30-day mortality rate was 23.5%. In the univariate analysis, patients who died within 30 days had higher National Institutes of Health Stroke Scale scores, higher CURB-65 scores, elevated instability of hemodynamic status, and lower Glasgow Coma Scale (GCS) scores. In Cox regression analysis, a GCS score of <9 on the day of pneumonia onset was only significant indicator for 30-day mortality (hazard ratio, 6.72; 95% confidence interval, 2.12-21.30, p = 0.001). Pneumonia after acute ischemic stroke is a severe complication. Once stroke-related pneumonia develops, neurologic assessment, CURB-65 score, and shock can be used to predict the ultimate prognosis. Copyright © 2012. Published by Elsevier B.V.

  12. Ischemic Gastropathic Ulcer Mimics Gastric Cancer

    PubMed Central

    Daher, Saleh; Lahav, Ziv; Rmeileh, Ayman Abu; Mizrahi, Meir

    2016-01-01

    Gastric ulcer due to mesenteric ischemia is a rare clinical finding. As a result, few reports of ischemic gastric ulcers have been reported in the literature. The diagnosis of ischemic gastropathy is seldom considered in patients presenting with abdominal pain and gastric ulcers. In this case report, we describe a patient with increasing abdominal pain, weight loss, and gastric ulcers, who underwent extensive medical evaluation and whose symptoms were resistant to medical interventions. Finally he was diagnosed with chronic mesenteric ischemia, and his clinical and endoscopic abnormalities resolved after surgical revascularization of both the superior mesenteric artery and the celiac trunk. PMID:27579191

  13. Ischemic Gastropathic Ulcer Mimics Gastric Cancer.

    PubMed

    Daher, Saleh; Lahav, Ziv; Rmeileh, Ayman Abu; Mizrahi, Meir; Khoury, Tawfik

    2016-01-01

    Gastric ulcer due to mesenteric ischemia is a rare clinical finding. As a result, few reports of ischemic gastric ulcers have been reported in the literature. The diagnosis of ischemic gastropathy is seldom considered in patients presenting with abdominal pain and gastric ulcers. In this case report, we describe a patient with increasing abdominal pain, weight loss, and gastric ulcers, who underwent extensive medical evaluation and whose symptoms were resistant to medical interventions. Finally he was diagnosed with chronic mesenteric ischemia, and his clinical and endoscopic abnormalities resolved after surgical revascularization of both the superior mesenteric artery and the celiac trunk.

  14. Anterior ischemic optic neuropathy following dengue fever

    PubMed Central

    Ramakrishnan, Reshma; Shrivastava, Saurabh; Deshpande, Shrikant; Patkar, Priyanka

    2016-01-01

    Dengue fever is caused by a flavivirus. This infection is endemic in the tropics and warm temperate regions of the world. Ocular manifestations of dengue fever include subconjunctival, vitreous, and retinal haemorrhages; posterior uveitis; optic neuritis; and maculopathies, haemorrhage, and oedema. However anterior ischemic optic neuropathy is a rare presentation. Optic nerve ischemia most frequently occurs at the optic nerve head, where structural crowding of nerve fibers and reduction of the vascular supply may combine to impair perfusion to a critical degree and produce optic disc oedema. Here we present a case of anterior ischemic optic neurapathy associated with dengue fever. PMID:27843231

  15. Anterior ischemic optic neuropathy following dengue fever.

    PubMed

    Ramakrishnan, Reshma; Shrivastava, Saurabh; Deshpande, Shrikant; Patkar, Priyanka

    2016-01-01

    Dengue fever is caused by a flavivirus. This infection is endemic in the tropics and warm temperate regions of the world. Ocular manifestations of dengue fever include subconjunctival, vitreous, and retinal haemorrhages; posterior uveitis; optic neuritis; and maculopathies, haemorrhage, and oedema. However anterior ischemic optic neuropathy is a rare presentation. Optic nerve ischemia most frequently occurs at the optic nerve head, where structural crowding of nerve fibers and reduction of the vascular supply may combine to impair perfusion to a critical degree and produce optic disc oedema. Here we present a case of anterior ischemic optic neurapathy associated with dengue fever.

  16. Flow Augmentation in Acute Ischemic Stroke.

    PubMed

    Yadollahikhales, Golnaz; Borhani-Haghighi, Afshin; Torabi-Nami, Mohammad; Edgell, Randall; Cruz-Flores, Salvador

    2016-01-01

    There is an urgent need for additional therapeutic options for acute ischemic stroke considering the major pitfalls of the options available. Herein, we briefly review the role of cerebral blood flow, collaterals, vasoreactivity, and reperfusion injury in acute ischemic stroke. Then, we reviewed pharmacological and interventional measures such as volume expansion and induced hypertension, intra-aortic balloon counterpulsation, partial aortic occlusion, extracranial-intracranial carotid bypass surgery, sphenopalatine ganglion stimulation, and transcranial laser therapy with regard to their effects on flow augmentation and neuroprotection. © The Author(s) 2014.

  17. [A case of myocardiopathy with hypothiaminemia exacerbated by imiparmine].

    PubMed

    Gaudeau, S; Derrida, J P; Tillement, J P; Vernant, P

    1976-10-01

    The authors report a case of a lady of 45 years of age who presented with a cardiomyopathy with hypothiaminaemia which had been made considerably worse by treatment with imipramine. Once treatment with the antidepressant was stopped, her condition returned to its previous status. The very high plasma imipramine level recorded in his case is undoubtedly the reason for the cardiac toxicity. The mechanism and role of hypothiaminaemia have not far been explained logically.

  18. [Chronologic study of signs of myocardiopathy in progressive muscular dystrophy].

    PubMed

    Barona Zamora, P; Narbona García, J; Alvarez Gómez, M J; Fidalgo Andrés, M L; Sáenz de Buruaga, J; Villa Elizaga, I

    1993-02-01

    In order to analyze the evolution of cardiomyopathy in progressive muscular dystrophies, thirty-three patients (17 with Duchenne type, 11 with Becker type and 5 with the autosomal recessive type dystrophy) were studied retrospectively. Cardiac and systemic follow-up every 3-6 months was made in 29 patients. The electrocardiogram was the first test that became altered, followed by the echocardiogram and thoracic radiograph and finally heart failure manifestations. There was a direct correlation between age and the appearance of abnormal cardiac tests. Electrocardiographic alterations, in patients who were less than 12.5 years of age, were significantly more frequent in the group with Duchenne dystrophy that in the no-Duchenne group. In regards to the appearance of the echocardiographic and radiographic abnormalities, there were no significant differences between the two groups. However, we have noticed a trend towards a more frequent and earlier presentation of these abnormalities in the Duchenne's muscular dystrophy than in the no-Duchenne group.

  19. Rehabilitation Outcomes: Ischemic versus Hemorrhagic Strokes

    PubMed Central

    Perna, Robert; Temple, Jessica

    2015-01-01

    Background. Ischemic and hemorrhagic strokes have different pathophysiologies and possibly different long-term cerebral and functional implications. Hemorrhagic strokes expose the brain to irritating effects of blood and ischemic strokes reflect localized or diffuse cerebral vascular pathology. Methods. Participants were individuals who suffered either an ischemic (n = 172) or hemorrhagic stroke (n = 112) within the past six months and were involved in a postacute neurorehabilitation program. Participants completed three months of postacute neurorehabilitation and the Mayo Portland Adaptability Inventory-4 (MPAI-4) at admission and discharge. Admission MPAI-4 scores and level of functioning were comparable. Results. Group ANOVA comparisons show no significant group differences at admission or discharge or difference in change scores. Both groups showed considerably reduced levels of productivity/employment after discharge as compared to preinjury levels. Conclusions. Though the pathophysiology of these types of strokes is different, both ultimately result in ischemic injuries, possibly accounting for lack of findings of differences between groups. In the present study, participants in both groups experienced similar functional levels across all three MPAI-4 domains both at admission and discharge. Limitations of this study include a highly educated sample and few outcome measures. PMID:26246694

  20. Unruptured cerebral aneurysms presenting with ischemic events.

    PubMed

    McLaughlin, Nancy; Bojanowski, Michel W

    2008-11-01

    Patients harboring an unruptured cerebral aneurysm may present with ischemic events. The goal of this study is to assess the clinical and radiological characteristics and the outcome following treatment of these patients. The study population included 463 patients with unruptured cerebral aneurysms treated between January 2000 and November 2006. Patients with aneurysms manifesting with ischemic events were included. Outcome was assessed 12 months following aneurysm treatment using the modified Rankin scale. Eleven patients were included in this series. An acute ischemic lesion in the symptomatic territory was demonstrated in six patients. The aneurysms were located on the internal carotid artery (n=4), middle cerebral artery (n=4), superior cerebellar artery (n=2) and basilar artery (n=1). They measured 10 mm or less (n=7); 11-20 mm (n=2); more than 21 mm (n=2). Five aneurysms were partially thrombosed on imaging. Five patients were referred for coiling. Of these, one patient had an unsuccessful coiling attempt, one had a residual neck, and three presented an aneurysm recurrence. Six patients were treated surgically. Symptomatic thromboembolism occurred after surgery in three patients. Complete aneurysm exclusion was documented in five of six operated patients. Nine of the ten treated patients had a favorable outcome. Even though aneurysms presenting with ischemic events are often small and located on the anterior circulation, in this series the risk of thromboembolic events following aneurysm treatment is noteworthy. This information is relevant given the possible benign natural history in terms of stroke and risk of bleeding for some of these aneurysms.

  1. Colonic ischemic necrosis following therapeutic embolization.

    PubMed

    Shenoy, S S; Satchidanand, S; Wesp, E H

    1981-01-01

    Transcatheter embolization of the middle colic artery for diverticular bleeding was followed by ischemic necrosis in the transverse colon at the site of previous anastomosis and stricture formation. This is a potential complication of intra-arterial embolization for colonic bleeding.

  2. Luxury perfusion following anterior ischemic optic neuropathy.

    PubMed

    Friedland, S; Winterkorn, J M; Burde, R M

    1996-09-01

    We present five patients who developed luxury perfusion following anterior ischemic optic neuropathy in whom fluorescein angiography was misinterpreted as "capillary hemangioma" or neovascularization of the disc. In each case, the segment of disc hyperemia corresponded to a spared region of visual field. Luxury perfusion represents a reparative autoregulatory reaction to ischemia.

  3. Does compensatory hyperparathyroidism predispose to ischemic stroke?

    PubMed

    Sato, Y; Kaji, M; Metoki, N; Satoh, K; Iwamoto, J

    2003-02-25

    Parathyroid hormone (PTH) is vasoactive, and the endothelium is one of the target tissues of this hormone. Hyperparathyroidism is frequently associated with hypertension. To determine if hyperparathyroidism, which develops particularly in elderly women as a compensatory mechanism to osteoporosis, may be a risk factor for ischemic stroke. Serum PTH levels and bone mineral density (BMD) in 107 elderly patients with ischemic stroke (>or=65 years old) were assessed on the day of onset. The control group consisted of 107 healthy volunteers matched for age and sex. BMD was significantly lower and serum PTH higher in female stroke patients than in control subjects; there was a negative correlation between these two measurements. One-third of the female stroke patients had a serum PTH level higher than the mean + 2 SD of the control subjects (high PTH group), and the interval between menopause and the stroke was significantly longer in the high PTH group than in the normal PTH group. Multiple logistic analyses revealed hypertension and ischemic heart disease were more prevalent in the high PTH group. BMD and PTH were normal in male stroke patients. High serum PTH level may be associated with high incidence of ischemic stroke in women, possibly through the increased incidence of hypertension.

  4. Coffee and acute ischemic stroke onset

    PubMed Central

    Mostofsky, E.; Schlaug, G.; Mukamal, K.J.; Rosamond, W.D.

    2010-01-01

    Objective: Prior research suggests an acutely elevated risk of myocardial infarction and sudden cardiac death in the hour after coffee intake. However, the risk of ischemic stroke associated with transient exposure to coffee remains unclear. We hypothesized that caffeine intake is associated with a transiently increased risk of ischemic stroke. Methods: In this multicenter case-crossover study, we interviewed 390 subjects (209 men, 181 women) between January 2001 and November 2006 a median of 3 days after acute ischemic stroke. Each subject's coffee consumption in the hour before stroke symptoms was compared with his or her usual frequency of consumption in the prior year. Results: Of the 390 subjects, 304 (78%) drank coffee in the prior year, 232 within 24 hours and 35 within 1 hour of stroke onset. The relative risk (RR) of stroke in the hour after consuming coffee was 2.0 (95% confidence interval [CI], 1.4–2.8; p < 0.001). There was no apparent increase in risk in the hour following consumption of caffeinated tea (RR = 0.9, 95% CI 0.4–2.0; p = 0.85) or cola (RR = 1.0, 95% CI 0.4–2.4; p = 0.95). The association between ischemic stroke in the hour after coffee consumption was only apparent among those consuming ≤1 cup per day but not for patients who consumed coffee more regularly (p for trend = 0.002). Relative risks remained similar when the sample was restricted to those who were not simultaneously exposed to other potential triggers and the results remained significant after stratifying by time of day. Conclusion: Coffee consumption transiently increases the risk of ischemic stroke onset, particularly among infrequent drinkers. PMID:20881275

  5. Remote Ischemic Conditioning and Renal Protection.

    PubMed

    Giannopoulos, Georgios; Vrachatis, Dimitrios A; Panagopoulou, Vasiliki; Vavuranakis, Manolis; Cleman, Michael W; Deftereos, Spyridon

    2017-07-01

    Over the course of the last 2 decades, the concept of remote ischemic conditioning (RIC) has attracted considerable research interest, because RIC, in most of its embodiments offers an inexpensive way of protecting tissues against ischemic damage inflicted by a number of medical conditions or procedures. Acute kidney injury (AKI) is a common side effect in the context of various medical procedures, and RIC has been suggested as a means of reducing its incidence. Outcomes regarding kidney function have been reported in numerous studies that evaluated the effects of RIC in a variety of settings (eg, cardiac surgery, interventions requiring intravenous administration of contrast media). Although several individual studies have implied a beneficial effect of RIC in preserving kidney function, 3 recently published randomized controlled trials evaluating more than 1000 patients each (Effect of Remote Ischemic Preconditioning in the Cardiac Surgery, Remote Ischaemic Preconditioning for Heart Surgery, and ERICCA) were negative. However, AKI or any other index of renal function was not a stand-alone primary end point in any of these trials. On the other hand, a range of meta-analyses (each including thousands of participants) have reported mixed results, with the most recent among them showing benefit from RIC, pinpointing at the same time a number of shortcomings in published studies, adversely affecting the quality of available data. The present review provides a critical appraisal of the current state of this field of research. It is the opinion of the authors of this review that there is a clear need for a common clinical trial framework for ischemic conditioning studies. If the current babel of definitions, procedures, outcomes, and goals persists, it is most likely that soon ischemic conditioning will be "yesterday's news" with no definitive conclusions having been reached in terms of its real clinical utility.

  6. Impact of early statin therapy in patients with ischemic stroke or transient ischemic attack.

    PubMed

    Chen, P-S; Cheng, C-L; Kao Yang, Y-H; Yeh, P-S; Li, Y-H

    2014-01-01

    Statin therapy has demonstrated benefits in ischemic stroke patients. However, little is known about whether the timing of statin initiation affects clinical outcomes. The possible association of statin use and cerebral hemorrhage is also a concern for early statin therapy after stroke. The objective of this study was to evaluate the efficacy and safety of the initiation timing of statins in acute ischemic stroke. A cohort study was performed using 5-year National Health Insurance Research Database in Taiwan. Patients without prior statin therapy admitted for their new ischemic stroke or transient ischemic attack (TIA) were enrolled. Patients were recognized as inhospital use group (2019 patients, statin initiation during hospitalization), intermediate use group (2266 patients, statin initiation within 1 year after discharge) or late use group (2958 patients, statin initiation 1 year later after discharge). The study endpoint was the composite outcome of ischemic stroke, TIA, hemorrhagic stroke, or acute coronary event. As compared with inhospital use, patients with late use had a 49% increased risk (adjusted HR: 1.49, 95% CI: 1.26-1.76) of composite endpoint. In contrast, patients with intermediate use had similar risk of endpoint as those with inhospital use. The risk of cerebral hemorrhage was similar in patients receiving inhospital, intermediate, or late statin treatment. In acute ischemic stroke, patients receiving late statin treatment carried a poorer clinical outcome than those with earlier statin initiation. Inhospital statin use after an acute ischemic stroke did not increase the risk of cerebral hemorrhage. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Stem cell transplantation for ischemic stroke.

    PubMed

    Boncoraglio, Giorgio Battista; Bersano, Anna; Candelise, Livia; Reynolds, Brent A; Parati, Eugenio A

    2010-09-08

    Studies in animal models of ischemic stroke have shown that stem cells transplanted into the brain can lead to functional improvement. However, to date, evidence for the benefits of stem cell transplantation in ischemic stroke patients is lacking. To assess the efficacy and safety of stem cell transplantation compared with conventional treatments in patients with ischemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched February 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (1966 to August 2008), EMBASE (1980 to August 2008), Science Citation Index (1900 to August 2008), and BIOSIS (1926 to August 2008). We handsearched potentially relevant conference proceedings, screened reference lists, and searched ongoing trials and research registers (last searched November 2008). We also contacted individuals active in the field and stem cell manufacturers (last contacted December 2008). We included randomized controlled trials (RCTs) recruiting patients with ischemic stroke, in any phase of the disease, and an ischemic lesion confirmed by computerized tomography or magnetic resonance imaging scan. We included all types of stem cell transplantation regardless of cell source (autograft, allograft, or xenograft; embryonic, fetal, or adult; from brain or other tissues), route of cell administration (systemic or local), and dosage. The primary outcome was efficacy (assessed as combined functional outcome or disability and dependency) at longer follow-up (minimum six months). Secondary outcomes included post-procedure safety outcomes (death, worsening of neurological deficit, infections and neoplastic transformation). Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional information. We identified three very small RCTs. Two are still awaiting classification because only subgroups of patients could be included in this meta

  8. Protection of retinal function by sulforaphane following retinal ischemic injury.

    PubMed

    Ambrecht, Lindsay A; Perlman, Jay I; McDonnell, James F; Zhai, Yougang; Qiao, Liang; Bu, Ping

    2015-09-01

    Sulforaphane, a precursor of glucosinolate in cruciferous vegetables such as broccoli and cauliflower, has been shown to protect brain ischemic injury. In this study, we examined the effect of systemic administration of sulforaphane on retinal ischemic reperfusion injury. Intraocular pressure was elevated in two groups of C57BL/6 mice (n = 8 per group) for 45 min to induce retinal ischemic reperfusion injury. Following retinal ischemic reperfusion injury, vehicle (1% DMSO saline) or sulforaphane (25 mg/kg/day) was administered intraperitoneally daily for 5 days. Scotopic electroretinography (ERG) was used to quantify retinal function prior to and one-week after retinal ischemic insult. Retinal morphology was examined one week after ischemic insult. Following ischemic reperfusion injury, ERG a- and b-wave amplitudes were significantly reduced in the control mice. Sulforaphane treatment significantly attenuated ischemic-induced loss of retinal function as compared to vehicle treated mice. In vehicle treated mice, ischemic reperfusion injury produced marked thinning of the inner retinal layers, but the thinning of the inner retinal layers appeared significantly less with sulforaphane treatment. Thus, sulforaphane may be beneficial in the treatment of retinal disorders with ischemic reperfusion injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Pathways for ischemic cytoprotection: Role of sirtuins in caloric restriction, resveratrol, and ischemic preconditioning

    PubMed Central

    Morris, Kahlilia C; Lin, Hung Wen; Thompson, John W; Perez-Pinzon, Miguel A

    2011-01-01

    Caloric restriction (CR), resveratrol, and ischemic preconditioning (IPC) have been shown to promote protection against ischemic injury in the heart and brain, as well as in other tissues. The activity of sirtuins, which are enzymes that modulate diverse biologic processes, seems to be vital in the ability of these therapeutic modalities to prevent against cellular dysfunction and death. The protective mechanisms of the yeast Sir2 and the mammalian homolog sirtuin 1 have been extensively studied, but the involvement of other sirtuins in ischemic protection is not yet clear. We examine the roles of mammalian sirtuins in modulating protective pathways against oxidative stress, energy depletion, excitotoxicity, inflammation, DNA damage, and apoptosis. Although many of these sirtuins have not been directly implicated in ischemic protection, they may have unique roles in enhancing function and preventing against stress-mediated cellular damage and death. This review will include in-depth analyses of the roles of CR, resveratrol, and IPC in activating sirtuins and in mediating protection against ischemic damage in the heart and brain. PMID:21224864

  10. Cannabis, ischemic stroke, and transient ischemic attack: a case-control study.

    PubMed

    Barber, Peter Alan; Pridmore, Heidi M; Krishnamurthy, Venkatesh; Roberts, Sally; Spriggs, David A; Carter, Kristie N; Anderson, Neil E

    2013-08-01

    There is a temporal relationship between cannabis use and stroke in case series and population-based studies. Consecutive stroke patients, aged 18 to 55 years, who had urine screens for cannabis were compared with a cohort of control patients admitted to hospital without cardiovascular or neurological diagnoses. One hundred sixty of 218 (73%) ischemic stroke/transient ischemic attack patients had urine drug screens (100 men; mean [SD] age, 44.8 [8.7] years). Twenty-five (15.6%) patients had positive cannabis drug screens. These patients were more likely to be men (84% versus 59%; χ2: P=0.016) and tobacco smokers (88% versus 28%; χ2: P<0.001). Control urine samples were obtained from 160 patients matched for age, sex, and ethnicity. Thirteen (8.1%) control participants tested positive for cannabis. In a logistic regression analysis adjusted for age, sex, and ethnicity, cannabis use was associated with increased risk of ischemic stroke/transient ischemic attack (odds ratio, 2.30; 95% confidence interval, 1.08-5.08). However after adjusting for tobacco use, an association independent of tobacco could not be confirmed (odds ratio, 1.59; 95% confidence interval, 0.71-3.70). This study provides evidence of an association between a cannabis lifestyle that includes tobacco and ischemic stroke. Further research is required to clarify whether there is an association between cannabis and stroke independent of tobacco. http://www.anzctr.org.au. Unique identifier: ACTRN12610000198022.

  11. Isolated naratriptan-associated ischemic colitis

    PubMed Central

    Nissan, George; Chaudhry, Priyanka; Rangasamy, Priya; Mudrovich, Steven

    2016-01-01

    We report a 41-year-old woman who developed histology- and colonoscopy-proven ischemic colitis with the use of naratriptan not exceeding the maximum 2 doses a day and 3 days per week and without a known medical or cardiovascular history. By exclusion of other causes of colonic ischemia, naratriptan was considered the sole causal agent. Discontinuation of naratriptan resulted in a complete clinical recovery. To date, our patient is the youngest known patient to develop ischemic colitis on isolated naratriptan in the setting of no known medical risk factors or predisposing medical condition. Even though triptans are commonly used for the abortive treatment of migraine headaches, such a reported side effect is rare; however, careful assessment and individual patient-based treatment is advised. PMID:27695179

  12. Aspirin resistant patients with recent ischemic stroke.

    PubMed

    Castilla-Guerra, L; Navas-Alcántara, M S; Fernández-Moreno, M C

    2014-04-01

    Some patients with a recent ischemic stroke who are being treated with aspirin as an antiaggregant suffer a new ischemic stroke. These patients (15-25%) have been called unresponsive to aspirin or aspirin resistant. The aspirin-resistant patients have a four-time greater risk of suffering a stroke. Furthermore, these strokes are generally more severe, with increased infarct volume and greater risk of recurrence. There is currently no ideal laboratory test to detect the resistance to the antiaggregant effect of aspirin. The study of resistance to aspirin would only be indicated in selected cases. In these patients, one should first rule out any "pseudo-resistance" to aspirin (lack of compliance, concomitant treatments that interfere with the action of the aspirin). Copyright © 2013 Elsevier España, S.L. All rights reserved.

  13. Ventricular tachycardia in ischemic heart disease substrates

    PubMed Central

    Ajijola, Olujimi A.; Tung, Roderick; Shivkumar, Kalyanam

    2014-01-01

    Advances in the treatment of myocardial infarction (MI) have improved survival after ischemic cardiac injury. Post-infarct structural and functional remodeling results in electrophysiologic substrates at risk for monomorphic ventricular tachycardia (MMVT). Characterization of this substrate using a variety of clinical and investigative tools has improved our understanding of MMVT circuits, and has accelerated the development of device and catheter-based therapies aimed at identification and elimination of this arrhythmia. This review will discuss the central role of the ischemic heart disease substrate in the development MMVT. Electrophysiologic characterization of the post-infarct myocardium using bipolar electrogram amplitudes to delineate scar border zones will be reviewed. Functional electrogram determinants of reentrant circuits such as isolated late potentials will be discussed. Strategies for catheter ablation of reentrant ventricular tachycardia, including structural and functional targets will also be examined, as will the role of the epicardial mapping and ablation in the management of recurrent MMVT. PMID:24568826

  14. Cost and Outcome in Pediatric Ischemic Stroke.

    PubMed

    Hamilton, William; Huang, Haijuan; Seiber, Eric; Lo, Warren

    2015-10-01

    The cost of childhood stroke receives little notice. The authors examined potential drivers of cost and outcome to test whether (1) neonatal strokes cost less than childhood strokes, (2) associated diseases influence cost, (3) arterial ischemic stroke is more costly than sinovenous thrombosis, and (4) cost correlates with outcome. The authors reviewed records of 111 children who sustained arterial ischemic stroke or sinovenous thrombosis between 2005 and 2010 to identify costs for the following year. They assessed outcomes in 46 with the Recovery and Recurrence Questionnaire and the Pediatric Quality of Life Inventory. Neonatal strokes cost less than childhood stroke. Strokes associated with congenital heart disease or vasculopathy cost the most, while perinatal or idiopathic strokes cost the least. Higher costs are correlated with worse impairment and poorer quality of life. Stroke etiology significantly influences the cost of pediatric stroke. Future cost-benefit studies must consider etiology when estimating the incremental costs associated with stroke.

  15. Modern medical management of acute ischemic stroke.

    PubMed

    Goldstein, Larry B

    2014-01-01

    The modern management of patients with ischemic stroke begins by having a system in place that organizes the provision of preventive, acute treatment, and rehabilitative services. In the acute setting, initial evaluation is aimed at rapidly establishing a diagnosis by excluding stroke mimics, distinguishing between ischemic and hemorrhagic strokes, and determining if the patient is a candidate for treatment with intravenous tissue plasminogen activator (IV-tPA, alteplase). In some centers, select patients who do not qualify for administration of IV-tPA may be considered for endovascular intervention. General measures include the use of platelet antiaggregants, treatment of fever, blood pressure management, and continuation of statins if the patient has already been taking them. Post-acute evaluation and management is aimed at secondary prevention and optimizing recovery, including recognition and treatment of post-stroke depression.

  16. Molecular chaperones and hypoxic-ischemic encephalopathy.

    PubMed

    Hua, Cong; Ju, Wei-Na; Jin, Hang; Sun, Xin; Zhao, Gang

    2017-01-01

    Hypoxic-ischemic encephalopathy (HIE) is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway. Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century. Hypothermia, xenon gas treatment, the use of melatonin and erythropoietin, and hypoxic-ischemic preconditioning have proven effective in HIE patients. Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes. A large number of molecular chaperones are induced after brain ischemia and hypoxia, among which the heat shock proteins are the most important. Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects. Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations, assisting in the proper folding of newly synthesized polypeptides, regulating the degradation of misfolded proteins, inhibiting the aggregation of proteins, and by controlling the refolding of misfolded proteins. In addition, heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways, including the intrinsic pathway, the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway. Molecular chaperones play a key role in neuroprotection in HIE. In this review, we

  17. Molecular chaperones and hypoxic-ischemic encephalopathy

    PubMed Central

    Hua, Cong; Ju, Wei-na; Jin, Hang; Sun, Xin; Zhao, Gang

    2017-01-01

    Hypoxic-ischemic encephalopathy (HIE) is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway. Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century. Hypothermia, xenon gas treatment, the use of melatonin and erythropoietin, and hypoxic-ischemic preconditioning have proven effective in HIE patients. Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes. A large number of molecular chaperones are induced after brain ischemia and hypoxia, among which the heat shock proteins are the most important. Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects. Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations, assisting in the proper folding of newly synthesized polypeptides, regulating the degradation of misfolded proteins, inhibiting the aggregation of proteins, and by controlling the refolding of misfolded proteins. In addition, heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways, including the intrinsic pathway, the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway. Molecular chaperones play a key role in neuroprotection in HIE. In this review, we

  18. Hypoxic Ischemic Encephalopathy in the Term Infant

    PubMed Central

    Fatemi, Ali; Wilson, Mary Ann; Johnston, Michael V.

    2010-01-01

    Synopsis Hypoxia-ischemia in the perinatal period is an important cause of cerebral palsy and associated disabilities in children. There has been significant research progress in hypoxic-ischemic encephalopathy over the last two decades and many new molecular mechanisms have been identified. Despite all these advances, therapeutic interventions are still limited. In this review paper, we discuss a number of molecular pathways involved in hypoxia-ischemia, and potential therapeutic targets. PMID:19944838

  19. Stem cell therapy for ischemic heart diseases.

    PubMed

    Yu, Hong; Lu, Kai; Zhu, Jinyun; Wang, Jian'an

    2017-01-01

    Ischemic heart diseases, especially the myocardial infarction, is a major hazard problem to human health. Despite substantial advances in control of risk factors and therapies with drugs and interventions including bypass surgery and stent placement, the ischemic heart diseases usually result in heart failure (HF), which could aggravate social burden and increase the mortality rate. The current therapeutic methods to treat HF stay at delaying the disease progression without repair and regeneration of the damaged myocardium. While heart transplantation is the only effective therapy for end-stage patients, limited supply of donor heart makes it impossible to meet the substantial demand from patients with HF. Stem cell-based transplantation is one of the most promising treatment for the damaged myocardial tissue. Key recent published literatures and ClinicalTrials.gov. Stem cell-based therapy is a promising strategy for the damaged myocardial tissue. Different kinds of stem cells have their advantages for treatment of Ischemic heart diseases. The efficacy and potency of cell therapies vary significantly from trial to trial; some clinical trials did not show benefit. Diverged effects of cell therapy could be affected by cell types, sources, delivery methods, dose and their mechanisms by which delivered cells exert their effects. Understanding the origin of the regenerated cardiomyocytes, exploring the therapeutic effects of stem cell-derived exosomes and using the cell reprogram technology to improve the efficacy of cell therapy for cardiovascular diseases. Recently, stem cell-derived exosomes emerge as a critical player in paracrine mechanism of stem cell-based therapy. It is promising to exploit exosomes-based cell-free therapy for ischemic heart diseases in the future.

  20. Hydrophilic Polymer-associated Ischemic Enterocolitis.

    PubMed

    Chavez, Jesus A; Chen, Wei; Frankel, Wendy L; Arnold, Christina A

    2017-02-01

    Hydrophilic polymer coating of medical devices serves to lubricate the device and prevent device-related complications. The coating can be mechanically disrupted and result in downstream injury via presumed thromboembolism. This process has been reported in the brain, heart, lung, and skin, and has been replicated through animal studies and in vitro histologic processing of the polymer coating. We report the first description of hydrophilic polymer-associated ischemic enterocolitis in a series of 7 specimens (small bowel=2, colon=4, aortic thrombus=1) from 3 patients. We report a 4% incidence among all patients with an ischemic bowel resection between April 29, 2014 and August 8, 2016. All patients developed bowel ischemia within 1 day of aortic repair, and all bowel resection specimens showed polymers, mainly in the submucosal vessels in areas of extensive ischemia. The polymers appeared as basophilic, intravascular, serpiginous structures. In a patient who developed acute paralysis after the aortic repair, identical polymers were identified in the aortic thrombus and the ischemic bowel segment. We demonstrate that the polymers display an altered morphology over time and with various graft types, and that the degrading polymers are associated with a foreign body giant cell reaction. Special stains can aid in diagnosis, with the polymers turquoise on a colloidal iron stain, pink on von Kossa and mucicarmine stains, and pale blue on trichrome. Clinical follow-up was available up to 115 weeks: 1 patient died, and 2 are alive and well. In summary, we report a new diagnostic entity to be considered in the differential diagnosis of iatrogenic ischemic injuries in the gastrointestinal tract. Awareness of this entity is important to elucidate the cause of ischemia and to prevent misdiagnosis of the polymers and their associated giant cell reaction as a parasitic infection, granulomatous vasculitis, sarcoidosis, and idiopathic inflammatory bowel disease.

  1. Ischemic Colitis in an Endurance Runner

    PubMed Central

    Grames, Chase; Berry-Cabán, Cristóbal S.

    2012-01-01

    A 20-year-old female running the Marine Corps Marathon developed diarrhea at mile 12. After finishing the race she noted that she was covered in bloody stool. A local emergency department suspected ischemic colitis. After discharge, her primary care physician instructed her to discontinue the use of all nonsteroidal anti-inflammatory drugs. Her symptoms resolved and she returned to running without any complications. This paper describes the pathophysiology, diagnostic approach, and management options. PMID:23091744

  2. Promoting thrombolysis in acute ischemic stroke.

    PubMed

    Dirks, Maaike; Niessen, Louis W; van Wijngaarden, Jeroen D H; Koudstaal, Peter J; Franke, Cees L; van Oostenbrugge, Robert J; Huijsman, Robbert; Lingsma, Hester F; Minkman, Mirella M N; Dippel, Diederik W J

    2011-05-01

    Thrombolysis with intravenous recombinant tissue plasminogen activator is an effective treatment for acute ischemic stroke, but the number of treatable patients is limited. The PRomoting ACute Thrombolysis in Ischemic StrokE (PRACTISE) trial evaluated the effectiveness of a multidimensional implementation strategy for thrombolysis with intravenous recombinant tissue plasminogen activator in acute ischemic stroke. The PRACTISE trial was a national multicenter cluster-randomized controlled trial with randomization after pairwise matching. Twelve hospitals, both urban and community, academic and nonacademic, in the Netherlands participated. All patients admitted with stroke within 24 hours from onset of symptoms were registered. The intervention included 5 implementation meetings based on the Breakthrough Series model. The primary outcome was treatment with thrombolysis. Secondary outcomes were admission within 4 hours after onset of symptoms, death or disability at 3 months, and quality of life. Overall 5515 patients were included in the study' 308 patients (12.2%) in the control centers and 393 patients (13.1%) in the intervention centers were treated with thrombolysis (adjusted OR, 1.25; 95% CI, 0.93 to 1.68). Among the 1657 patients with ischemic stroke admitted within 4 hours from onset, 391 (44.5%) of 880 in the intervention centers were treated with thrombolysis and 305 (39.3%) of 777 in the control centers; the adjusted OR for treatment with thrombolysis was 1.58 (95% CI, 1.11 to 2.27). An intensive implementation strategy increases the proportion of patients with acute stroke treated with thrombolysis in real-life settings. An apparently pivotal factor in the improvement of the treatment rate is better application of contraindications for thrombolysis.

  3. White matter injury in ischemic stroke.

    PubMed

    Wang, Yuan; Liu, Gang; Hong, Dandan; Chen, Fenghua; Ji, Xunming; Cao, Guodong

    2016-06-01

    Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions.

  4. Neurovascular Regulation in the Ischemic Brain

    PubMed Central

    Jackman, Katherine

    2015-01-01

    Abstract Significance: The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. Recent Advances and Critical Issues: The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active responses such as cerebral autoregulation, which acts to maintain constant cerebral blood flow in response to changing blood pressure, and functional hyperemia, which couples blood supply with synaptic activity, allow the brain to maintain adequate cerebral perfusion in the face of varying supply or demand. In the presence of stroke risk factors, such as hypertension and diabetes, these protective processes are impaired and the susceptibility of the brain to ischemic injury is increased. One potential mechanism for the increased injury is that collateral flow arising from the normally perfused brain and supplying blood flow to the ischemic region is suppressed, resulting in more severe ischemia. Future Directions: Approaches to support collateral flow may ameliorate the outcome of focal cerebral ischemia by rescuing cerebral perfusion in potentially viable regions of the ischemic territory. Antioxid. Redox Signal. 22, 149–160. PMID:24328757

  5. Applicability of biomarkers in ischemic stroke.

    PubMed

    Castellanos, Mar; Serena, Joaquín

    2007-01-01

    Cerebral ischemia results in the activation of a cascade of molecular events as a result of which several substances with the potential characteristics of biomarkers are released into the peripheral blood. Although still in the research phase, the analysis of these biomarkers in the serum has proved to be useful for stroke diagnosis, as well as for the prediction of the evolution of the ischemic lesion and the clinical prognosis. In fact, the feasibility and applicability of a panel of biomarkers for the diagnosis of stroke has recently been tested. Biomarkers of excitotoxicity, inflammation and oxidative stress have been demonstrated as being useful in the prediction of ischemic lesion enlargement and secondary neurological deterioration. On the other hand, biomarkers of endothelial damage have been shown to be especially helpful in the prediction of hemorrhagic transformation of the ischemic lesion, both spontaneously and after the administration of thrombolytic therapy, as well as in the prediction of brain edema with the secondary development of malignant middle-cerebral-artery infarction. Moreover, coagulation and fibrinolytic-cascade markers have been reported as being correlated with the recanalization rate after the administration of thrombolysis, and they might therefore be useful in estimating the effectiveness of thrombolytic therapy. However, for these biomarkers to become applicable to routine clinical practice, faster tests to perform the analyses are required and further studies must be undertaken to validate and generalize the results.

  6. [Ischemic stroke in the young adult].

    PubMed

    Calvet, D

    2016-01-01

    Ischemic stroke is not rare in young adults since one in ten stroke patients are less than 50 years old. This incidence increased over the past last years, mainly due to the rise in the prevalence of traditional vascular risk factors in this sub-group of age but also of illegal drug use. Even though both survival and functional outcome of young stroke patients are better than those observed in older patients, socio-economic and quality of life consequences make this disease a main objective in terms of primary and secondary prevention. Identifying the cause of ischemic stroke in young adults is of major importance to prevent stroke recurrence. However, given the wide variety of potential underlying causes, the etiologic work-up of stroke in young adults requires a different approach from that in the elderly. In this context, a sequential diagnostic work-up is needed in order to optimize the yield of diagnostic tests, to reduce their cost and risks for the patient. Arterial dissection is the most frequent cause of stroke in young adults but other less frequent causes are numerous. Despite a comprehensive work-up, about one third of cases remains unexplained leading to the diagnosis of cryptogenic ischemic stroke.

  7. Blood Pressure in Acute Ischemic Stroke

    PubMed Central

    McManus, Michael

    2016-01-01

    Hypertension is present in up to 84% of patients presenting with acute stroke, and a smaller proportion of patients have blood pressures that are below typical values in the context of cerebral ischemia. Outcomes are generally worse in those who present with either low or severely elevated blood pressure. Several studies have provided valuable information about malignant trends in blood pressure during the transition from the acute to the subacute phase of stroke. It is not uncommon for practitioners in clinical practice to identify what appear to be pressure-dependent neurologic deficits. Despite physiologic and clinical data suggesting the importance of blood pressure modulation to support cerebral blood flow to ischemic tissue, randomized controlled trials have not yielded robust evidence for this in acute ischemic stroke. We highlight previous studies involving acute-stroke patients that have defined trends in blood pressure and that have evaluated the safety and efficacy of blood-pressure modulation in acute ischemic stroke. This overview reports the current status of this topic from the perspective of a stroke neurologist and provides a framework for future research. PMID:26833984

  8. Endovascular treatment of acute ischemic stroke.

    PubMed

    Leslie-Mazwi, Thabele; Rabinov, James; Hirsch, Joshua A

    2016-01-01

    Endovascular thrombectomy is an effective treatment for major acute ischemic stroke syndromes caused by major anterior circulation artery occlusions (commonly referred to as large vessel occlusion) and is superior to intravenous thrombolysis and medical management. Treatment should occur as quickly as is reasonably possible. All patients with moderate to severe symptoms (National Institutes of Health stroke scale >8) and a treatable occlusion should be considered. The use of neuroimaging is critical to exclude hemorrhage and large ischemic cores. Very shortly after stroke onset (<3 hours) computed tomography (CT) and CT angiography provide sufficient information to proceed; diffusion magnetic resonance imaging (MRI) is less reliable during this early stage. After 3 hours from onset diffusion MRI is the most reliable method to define ischemic core size and should be used in centers that can offer it rapidly. Recanalization is highly effective with a stentriever or using a direct aspiration technique, with the patient awake or under conscious sedation rather than general anesthesia, if it may be performed safely. After thrombectomy the patient should be admitted to an intensive care setting and inpatient rehabilitation undertaken as soon as feasible. Patient outcomes should be assessed at 3 months, preferably using the modified Rankin score. © 2016 Elsevier B.V. All rights reserved.

  9. Cardioprotection by remote ischemic conditioning: Mechanisms and clinical evidences

    PubMed Central

    Aimo, Alberto; Borrelli, Chiara; Giannoni, Alberto; Pastormerlo, Luigi Emilio; Barison, Andrea; Mirizzi, Gianluca; Emdin, Michele; Passino, Claudio

    2015-01-01

    In remote ischemic conditioning (RIC), several cycles of ischemia and reperfusion render distant organ and tissues more resistant to the ischemia-reperfusion injury. The intermittent ischemia can be applied before the ischemic insult in the target site (remote ischemic preconditioning), during the ischemic insult (remote ischemic perconditioning) or at the onset of reperfusion (remote ischemic postconditioning). The mechanisms of RIC have not been completely defined yet; however, these mechanisms must be represented by the release of humoral mediators and/or the activation of a neural reflex. RIC has been discovered in the heart, and has been arising great enthusiasm in the cardiovascular field. Its efficacy has been evaluated in many clinical trials, which provided controversial results. Our incomplete comprehension of the mechanisms underlying the RIC could be impairing the design of clinical trials and the interpretation of their results. In the present review we summarize current knowledge about RIC pathophysiology and the data about its cardioprotective efficacy. PMID:26516416

  10. Arterial Spin Label Imaging of Acute Ischemic Stroke and Transient Ischemic Attack

    PubMed Central

    Zaharchuk, Greg

    2011-01-01

    Since acute ischemic stroke and transient ischemic attack (TIA) are fundamentally disruptions of brain hemodynamics, neuroimaging of brain perfusion might be expected to be of clinical utility. Recently, a noncontrast method of measuring CBF using arterial spin labeling (ASL) has become feasible in the clinical setting. It has advantages when compared to dynamic susceptibility contrast (DSC) bolus contrast perfusion-weighted imaging (PWI) that include lack of exposure to gadolinium-based contrast materials, improved quantitation, and decreased sensitivity to susceptibility artifacts and motion. Drawbacks of ASL include reduced signal-to-noise (SNR) and high sensitivity to arterial transit delays. While deleterious for quantitative perfusion measurements, the sensitivity of ASL to late arriving blood can be beneficial to visualize collateral flow. This chapter will discuss ASL imaging findings in patients presenting with acute ischemic stroke and TIA, focusing on typical appearances, common artifacts, and comparisons with bolus contrast PWI. PMID:21640300

  11. New Treatments for Nonarteritic Anterior Ischemic Optic Neuropathy.

    PubMed

    Foroozan, Rod

    2017-02-01

    Despite increasing knowledge about the risk factors and clinical findings of nonarteritic anterior ischemic optic neuropathy (NAION), the treatment of this optic neuropathy has remained limited and without clear evidence-based benefit. Historical treatments of NAION are reviewed, beginning with the Ischemic Optic Neuropathy Decompression Trial. More recent treatments are placed within the historical context and illustrate the need for evidence-based therapy for ischemic optic neuropathy. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Evolving therapeutic targets in ischemic stroke: a concise review.

    PubMed

    Sugunan, Sinoy; Joseph, Diya Binoy; Rajanikant, G K

    2013-04-01

    Ischemic stroke is the leading cause of mortality and morbidity worldwide for which the assemblage of therapeutic interventions has remained outstandingly limited. Several new insights into the causes of neuronal death during ischemic event have led to the identification of some important novel targets for intervention. This article highlights some of the promising protein targets, which are in the validation process and have the potential to get translated into viable neurotherapeutics against ischemic stroke.

  13. Fractal analysis of the ischemic transition region in chronic ischemic heart disease using magnetic resonance imaging.

    PubMed

    Michallek, Florian; Dewey, Marc

    2017-04-01

    To introduce a novel hypothesis and method to characterise pathomechanisms underlying myocardial ischemia in chronic ischemic heart disease by local fractal analysis (FA) of the ischemic myocardial transition region in perfusion imaging. Vascular mechanisms to compensate ischemia are regulated at various vascular scales with their superimposed perfusion pattern being hypothetically self-similar. Dedicated FA software ("FraktalWandler") has been developed. Fractal dimensions during first-pass (FDfirst-pass) and recirculation (FDrecirculation) are hypothesised to indicate the predominating pathomechanism and ischemic severity, respectively. Twenty-six patients with evidence of myocardial ischemia in 108 ischemic myocardial segments on magnetic resonance imaging (MRI) were analysed. The 40th and 60th percentiles of FDfirst-pass were used for pathomechanical classification, assigning lesions with FDfirst-pass ≤ 2.335 to predominating coronary microvascular dysfunction (CMD) and ≥2.387 to predominating coronary artery disease (CAD). Optimal classification point in ROC analysis was FDfirst-pass = 2.358. FDrecirculation correlated moderately with per cent diameter stenosis in invasive coronary angiography in lesions classified CAD (r = 0.472, p = 0.001) but not CMD (r = 0.082, p = 0.600). The ischemic transition region may provide information on pathomechanical composition and severity of myocardial ischemia. FA of this region is feasible and may improve diagnosis compared to traditional noninvasive myocardial perfusion analysis. • A novel hypothesis and method is introduced to pathophysiologically characterise myocardial ischemia. • The ischemic transition region appears a meaningful diagnostic target in perfusion imaging. • Fractal analysis may characterise pathomechanical composition and severity of myocardial ischemia.

  14. Thromboelastography in patients with acute ischemic stroke.

    PubMed

    Elliott, Andrea; Wetzel, Jeremy; Roper, Tiffany; Pivalizza, Evan; McCarthy, James; Wallace, Cristina; Hess, Mary Jane; Peng, Hui; Rahbar, Mohammad H; Sangha, Navdeep; Grotta, James C

    2015-02-01

    Thromboelastography measures the dynamics of coagulation. There are limited data about thromboelastography in acute ischemic stroke other than a single study from 1974 suggesting that acute ischemic stroke patients are hypercoagulable. There have been no studies of thromboelastography in the thrombolytic era despite its potential usefulness as a measure of clot lysis. This study was designed to provide initial thromboelastography data in stroke patients before and after tissue plasminogen activator therapy and to provide the necessary preliminary data for further study of thromboelastography's ability to identify clot subtype and predict response to tissue plasminogen activator therapy. All acute ischemic stroke patients presenting between 11/2009 and 2/2011 eligible for tissue plasminogen activator therapy were screened and 56 enrolled. Blood was drawn before (52 patients) and 10 mins after tissue plasminogen activator bolus (30 patients). Demographics, vitals, labs, 24 h National Institutes of Health Stroke Scale, and computed tomography scan results were collected. Patients were compared with normal controls. Acute ischemic stroke patients had shorter R (4.8 ± 1.5 vs. 6.0 ± 1.7 min, P = 0.0004), greater α Angle (65.0 ± 7.6 vs. 61.5 ± 5.9°, P = 0.01), and shorter K (1.7 ± 0.7 vs. 2.1 ± 0.7 min, P = 0.002) indicating faster clotting. Additionally, a subset formed clots with stronger platelet-fibrin matrices. Treatment with tissue plasminogen activator resulted in reduction in all indices of clot strength (LY30 = 0 (0-0.4) vs. 94.4 (15.2-95.3) P < 0.0001); however, there was considerable variability in response. Thromboelastography demonstrates that many acute ischemic stroke patients are hypercoaguable. Thromboelastography values reflect variable clot subtype and response to tissue plasminogen activator. Further study based on these data will determine if thromboelastography is useful for measuring the dynamic aspects of clot formation and monitoring lytic

  15. The Influence of Diabetes Mellitus in Myocardial Ischemic Preconditioning.

    PubMed

    Rezende, Paulo Cury; Rahmi, Rosa Maria; Hueb, Whady

    Ischemic preconditioning (IP) is a powerful mechanism of protection discovered in the heart in which ischemia paradoxically protects the myocardium against other ischemic insults. Many factors such as diseases and medications may influence IP expression. Although diabetes poses higher cardiovascular risk, the physiopathology underlying this condition is uncertain. Moreover, although diabetes is believed to alter intracellular pathways related to myocardial protective mechanisms, it is still controversial whether diabetes may interfere with ischemic preconditioning and whether this might influence clinical outcomes. This review article looks at published reports with animal models and humans that tried to evaluate the possible influence of diabetes in myocardial ischemic preconditioning.

  16. Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

    PubMed Central

    Duanmu, Wang-sheng; Cao, Liu; Chen, Jing-yu; Ge, Hong-fei; Hu, Rong; Feng, Hua

    2016-01-01

    Ischemic postconditioning renders brain tissue tolerant to brain ischemia, thereby alleviating ischemic brain injury. However, the exact mechanism of action is still unclear. In this study, a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method. After 2 hours of ischemia, the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds. This procedure was repeated six times. Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia, and up-regulate acid-sensing ion channel 2a expression at the mRNA and protein level. These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia, which promotes neuronal tolerance to ischemic brain injury. PMID:27212927

  17. Migration of neural stem cells to ischemic brain regions in ischemic stroke in rats.

    PubMed

    Dai, Jiong; Li, Shan-Quan; Qiu, Yong-Ming; Xiong, Wen-Hao; Yin, Yu-Hua; Jia, Feng; Jiang, Ji-Yao

    2013-09-27

    An established rat model of ischemic stroke, produced by temporary middle cerebral artery occlusion and reperfusion (MCAO/R), was used in the evaluation of organ migration of intra-arterial (IA) transplantation of neural stem cells (NSCs). Immediately after transplantation, ischemic rats (n=8) transplanted with either NSCs (MCAO/R+NSC group) or NSC growth medium (MCAO/R+medium group) exhibited neurological dysfunction but rats in a sham+NSCs group (n=5) did not. During the post-operative period, neurological function improved to a similar extent in both MCAO/R groups. At 10 and 14 days post-transplantation, neurological function in the MCAO/R+NSC group was superior to that in the MCAO/R+medium group (p<0.001). Hematoxylin-eosin staining showed neuronal degeneration and necrosis in ischemic rats. Immunofluorescence staining revealed that NSCs had migrated to the frontal and parietal lobes, caudate, and putamen. Some cells had begun differentiating into neurons and astrocytes. Rat NSCs can migrate into the ischemic region, survive, and differentiate into astrocytes and neurons, and thereby potentially improve neurologic function after cerebral ischemia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Ischemic preconditioning. Experimental facts and clinical perspective.

    PubMed

    Post, H; Heusch, G

    2002-12-01

    Brief periods of non-lethal ischemia and reperfusion render the myocardium more resistant to subsequent ischemia. This adaption occurs in a biphasic pattern: the first being active immediately and lasting for 2-3 hrs (early preconditioning), the second starting at 24 hrs until 72 hrs after the initial ischemia (delayed preconditioning) and requiring genomic activation with de novo protein synthesis. Early preconditioning is more potent than delayed preconditioning in reducing infarct size; delayed preconditioning also attenuates myocardial stunning. Early preconditioning depends on the ischemia-induced release of adenosine and opioids and, to a lesser degree, also bradykinin and prostaglandins. These molecules activate G-protein coupled receptors, initiate the activation of KATP channels and generation of oxygen radicals, and stimulate a series of protein kinases with essential roles for protein kinase C, tyrosine kinases and members of the MAP kinase family. Delayed preconditioning is triggered by a similar sequence of events, but in addition essentially depends on eNOS-derived NO. Both early and pharmacological preconditioning can be pharmacologically mimicked by exogenous adenosine, opioids, NO and activators of protein kinase C. Newly synthetized proteins associated with delayed preconditioning comprise iNOS, COX-2, manganese superoxide dismutase and possibly heat shock proteins. The final mechanism of protection by preconditioning is yet unknown; energy metabolism, KATP channels, the sodium-proton exchanger, stabilisation of the cytoskeleton and volume regulation will be discussed. For ethical reasons, evidence for ischemic preconditioning in humans is hard to provide. Clinical findings that parallel experimental ischemic preconditioning are reduced ST-segment elevation and pain during repetitive PTCA or exercise tests, a better prognosis of patients in whom myocardial infarction was preceded by angina, and reduced serum markers of myocardial necrosis after

  19. Gene Variants Associated With Ischemic Stroke

    PubMed Central

    Luke, May M.; O’Meara, Ellen S.; Rowland, Charles M.; Shiffman, Dov; Bare, Lance A.; Arellano, Andre R.; Longstreth, W.T.; Lumley, Thomas; Rice, Kenneth; Tracy, Russell P.; Devlin, James J.; Psaty, Bruce M.

    2010-01-01

    Background and Purpose The purpose of this study was to determine whether 74 single nucleotide polymorphisms (SNPs), which had been associated with coronary heart disease, are associated with incident ischemic stroke. Methods Based on antecedent studies of coronary heart disease, we prespecified the risk allele for each of the 74 SNPs. We used Cox proportional hazards models that adjusted for traditional risk factors to estimate the associations of these SNPs with incident ischemic stroke during 14 years of follow-up in a population-based study of older adults: the Cardiovascular Health Study (CHS). Results In white CHS participants, the prespecified risk alleles of 7 of the 74 SNPs (in HPS1, ITGAE, ABCG2, MYH15, FSTL4, CALM1, and BAT2) were nominally associated with increased risk of stroke (one-sided P<0.05, false discovery rate=0.42). In black participants, the prespecified risk alleles of 5 SNPs (in KRT4, LY6G5B, EDG1, DMXL2, and ABCG2) were nominally associated with stroke (one-sided P<0.05, false discovery rate=0.55). The Val12Met SNP in ABCG2 was associated with stroke in both white (hazard ratio, 1.46; 90% CI, 1.05 to 2.03) and black (hazard ratio, 3.59; 90% CI, 1.11 to 11.6) participants of CHS. Kaplan-Meier estimates of the 10-year cumulative incidence of stroke were greater among Val allele homozygotes than among Met allele carriers in both white (10% versus 6%) and black (12% versus 3%) participants of CHS. Conclusions The Val12Met SNP in ABCG2 (encoding a transporter of sterols and xenobiotics) was associated with incident ischemic stroke in white and black participants of CHS. PMID:19023099

  20. Myocardial Ischemic Memory Imaging With Molecular Echocardiography

    PubMed Central

    Villanueva, Flordeliza S.; Lu, Erxiong; Bowry, Shivani; Kilic, Sevgi; Tom, Eric; Wang, Jianjun; Gretton, Joan; Pacella, John J.; Wagner, William R.

    2014-01-01

    Background Diagnosing acute coronary syndrome in patients presenting with chest discomfort is a challenge. Because acute myocardial ischemia/reperfusion is associated with endothelial upregulation of leukocyte adhesion molecules, which persist even after ischemia has resolved, we hypothesized that microbubbles designed to adhere to endothelial selectins would permit echocardiographic identification of recently ischemic myocardium. Methods and Results Lipid microbubbles (diameter, 3.3±1.7 μm) were synthesized. The selectin ligand sialyl Lewisx was conjugated to the microbubble surface (MBsLex). Control bubbles (MBCTL) bore surface Lewisx or sialyl Lewisc. Intravital microscopy of mouse cremaster muscle was performed after intravenous injection of MBsLex (n=11) or MBCTL (n=9) with or without prior intrascrotal tumor necrosis factor–α. There was greater adhesion of MBsLex to inflamed versus noninflamed endothelium (P=0.0081). Rats (n=12) underwent 15 minutes of anterior descending coronary artery occlusion. After 30 minutes and 1 hour of reperfusion, high-mechanical-index nonlinear echocardiographic imaging was performed in which single frames were acquired at 3.5 and 4 minutes after intravenous injection of MBsLex or MBCTL. Video intensity at 4 minutes was subtracted from that at 3.5 minutes to derive target-specific acoustic signal. MBsLex caused greater opacification in postischemic versus nonischemic myocardium at both time points (P≤0.002). Immunostaining confirmed endothelial P-selectin expression in the ischemic bed. Conclusions Echocardiographic identification of recently ischemic myocardium is possible using ultrasound contrast agents targeted to selectins. This may offer a new approach to the more timely and precise diagnosis of acute coronary syndrome in patients presenting with chest pain of uncertain cardiac origin. PMID:17210843

  1. Antithrombotic and Thrombolytic Therapy for Ischemic Stroke

    PubMed Central

    Lansberg, Maarten G.; O’Donnell, Martin J.; Khatri, Pooja; Lang, Eddy S.; Nguyen-Huynh, Mai N.; Schwartz, Neil E.; Sonnenberg, Frank A.; Schulman, Sam; Vandvik, Per Olav; Spencer, Frederick A.; Alonso-Coello, Pablo; Guyatt, Gordon H.

    2012-01-01

    Objectives: This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA). Methods: We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence. Results: In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B). Conclusions: These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes. PMID:22315273

  2. Ischemic Neuropathy Associated with Livedoid Vasculitis

    PubMed Central

    Kim, Jee-Eun; Park, Su-Yeon; Sinn, Dong In; Kim, Sung-Min; Hong, Yoon-Ho; Park, Kyung Seok; Lee, Kwang-Woo

    2011-01-01

    Background Livedoid vasculitis is a chronic dermatological problem with an unclear etiology. Clinical findings are petechiae with painful ulcers in both lower extremities, which heal to become hyperpigmented and porcelain-white satellite lesions. There are only a few reported cases of livedoid vasculitis presenting in combination with peripheral neuropathy. Case Report We report the first case of a Korean patient presenting with mononeuritis multiplex combined with livedoid vasculitis, which was confirmed by electrophysiological and pathological studies. Conclusions Our report supports the possible vaso-occlusive etiology of livedoid vasculitis in multifocal ischemic neuropathy. PMID:22259622

  3. Cardiogenic embolism producing crescendo transient ischemic attacks.

    PubMed

    Geraghty, Patrick J; Oak, Jack; Choi, Eric T

    2005-09-01

    Lateralizing, repetitive transient ischemic attacks are characteristic of symptomatic carotid bifurcation atherosclerotic plaques. We report a case in which a cardiogenic embolus, after lodging at the left carotid bifurcation, produced crescendo episodes of expressive aphasia and mild right upper extremity weakness. Complete neurological recovery was achieved following emergent carotid embolectomy and endarterectomy. This case demonstrates that the laminar nature of internal carotid blood flow may result in the localization of embolic events to a single region of the cerebral vasculature, regardless of the source lesion in the carotid artery. The role of endoluminal techniques in the diagnosis and management of such lesions is discussed.

  4. [Pulmonary function in chronic ischemic cardiopathy].

    PubMed

    Martínez Guerra, M L; Gómez González, A; Fernández Bonetti, P; Martínez Ríos, M A

    1983-01-01

    Twenty patients with heart disease were prospectively studied. Seven of them had an old myocardial infarction and thirteen, ischemic symptoms without infarction. Pulmonary function was studied focusing on small airway disease and gas exchange abnormalities. Our results showed that a mild degree of abnormality exists as reflected by bronchial obstruction with origin in small airways, V/Q disturbed and hypoxemia. In 88% these seem to be related to left ventricular disfunction. Twenty four hours after pulmonary function test all patients underwent left heart catheterization with coronarography and ventriculography.

  5. Fyn in Neurodevelopment and Ischemic Brain Injury

    PubMed Central

    Knox, Renatta; Jiang, Xiangning

    2016-01-01

    The Src Family kinases (SFKs) are nonreceptor protein tyrosine kinases that are implicated in many normal and pathological processes in the nervous system. The SFKs Fyn, Src, Yes, Lyn and Lck are expressed in the brain. This review will focus on Fyn, as Fyn mutant mice have striking phenotypes in the brain and Fyn has been shown to be involved in ischemic brain injury in adult rodents, and with our work, in neonatal animals. An understanding of Fyn’s role in neurodevelopment and disease will allow researchers to target pathological pathways while preserving protective ones. PMID:25720756

  6. Ischemic cardiac complications following G-CSF.

    PubMed

    Eckman, Peter M; Bertog, Stefan C; Wilson, Robert F; Henry, Timothy D

    2010-07-01

    Granulocyte-colony stimulating factor (G-CSF) is commonly used in bone marrow transplant donors to increase the number of circulating progenitor cells. G-CSF has also been studied following myocardial infarction, but concern has been raised about the risks of G-CSF administration in patients with coronary artery disease. We present two cases of ischemic cardiac complications that are likely to be related to administration of G-CSF and provide a contemporary overview of the literature on the cardiovascular risks of G-CSF.

  7. Oxidative stress--assassin behind the ischemic stroke.

    PubMed

    Pradeep, Hanumanthappa; Diya, Joseph B; Shashikumar, Shivaiah; Rajanikant, Golgodu K

    2012-01-01

    Ischemic stroke is the second leading cause of death and disability worldwide and is associated with significant clinical and socioeconomic implications, emphasizing the need for effective therapies. Several neuroprotective strategies have failed in clinical trials because of poor knowledge of the molecular processes flanked with ischemic stroke. Therefore, uncovering the molecular processes involved in ischemic brain injury is of critical importance. Therapeutic strategies for ischemic stroke remain ineffective, though rapid advances occur in understanding the pathophysiology of the disease. The oxidative stress is one such high-potential phenomenon, the precise role of which needs to be understood during ischemic events. Nevertheless, the studies carried out in preclinical models of ischemic stroke have pointed to the major role of oxidative stress in exacerbating the ischemic injury. Oxidative stress leading to cell death requires generation of free radicals through multiple mechanisms, such as respiratory inhibition, Ca(2+) imbalance, excitotoxicity, reperfusion injury and inflammation. Free radicals are highly reactive to all the molecular targets: lipids, proteins and nucleic acids, modifying their chemical structure and generating oxidation-derived products. This review discusses molecular aspects of oxidative stress in ischemic stroke and catastrophes that set up as an aftermath of the trauma.

  8. Changes of resting cerebral activities in subacute ischemic stroke patients

    PubMed Central

    Wu, Ping; Zeng, Fang; Li, Yong-xin; Yu, Bai-li; Qiu, Li-hua; Qin, Wei; Li, Ji; Zhou, Yu-mei; Liang, Fan-rong

    2015-01-01

    This study aimed to detect the difference in resting cerebral activities between ischemic stroke patients and healthy participants, define the abnormal site, and provide new evidence for pathological mechanisms, clinical diagnosis, prognosis prediction and efficacy evaluation of ischemic stroke. At present, the majority of functional magnetic resonance imaging studies focus on the motor dysfunction and the acute stage of ischemic stroke. This study recruited 15 right-handed ischemic stroke patients at subacute stage (15 days to 11.5 weeks) and 15 age-matched healthy participants. A resting-state functional magnetic resonance imaging scan was performed on each subject to detect cerebral activity. Regional homogeneity analysis was used to investigate the difference in cerebral activities between ischemic stroke patients and healthy participants. The results showed that the ischemic stroke patients had lower regional homogeneity in anterior cingulate and left cerebrum and higher regional homogeneity in cerebellum, left precuneus and left frontal lobe, compared with healthy participants. The experimental findings demonstrate that the areas in which regional homogeneity was different between ischemic stroke patients and healthy participants are in the cerebellum, left precuneus, left triangle inferior frontal gyrus, left inferior temporal gyrus and anterior cingulate. These locations, related to the motor, sensory and emotion areas, are likely potential targets for the neural regeneration of subacute ischemic stroke patients. PMID:26109950

  9. Remote cardiac ischemic conditioning: underlying mechanisms and clinical applications.

    PubMed

    Gaspar, António; Leite-Moreira, Adelino F

    2012-01-01

    Despite a significant improvement in the care of acute coronary disease, mortality and morbidity remain important. One explanation for this lies in the fact that the very coronary reperfusion may paradoxically result in additional myocardial injury, through the so-called ischemia-reperfusion injury, partially mitigating the beneficial effects of myocardial reperfusion. Over the past two decades, numerous pharmacological interventions (such as the use of antioxidants, anti-inflammatory, magnesium, glucose/insulin/potassium, rapid normalization of pH) were studied in order to prevent ischemia-reperfusion injury. Despite the promising results obtained in animal experiments, attempts to transpose these results to humans, and consequently to clinical practice, have been disappointing. On the other hand, cardiac ischemic conditioning is an intervention that has produced positive results. Ischemic conditioning refers to the protection induced by short periods of ischemia followed by reperfusion, prior to a major ischemic event. Ischemic stimulus can be applied before (pre-conditioning), during (per-conditioning) or after (post-conditioning) the major ischemic event. An important finding regarding cardiac ischemic conditioning, was that protection could be induced remotely, introducing the concept of remote ischemic conditioning. In this paper, we proposed to review the mechanisms underlying remote ischemic cardiac conditioning and the possible clinical applications, considering more specifically pre and per-conditioning.

  10. Plasma biomarkers in the diagnosis of acute ischemic stroke.

    PubMed

    Kim, Myeong Hee; Kang, So Young; Kim, Myung Chun; Lee, Woo In

    2010-01-01

    Rapid diagnosis and timely treatment improves the outcome in patients with ischemic stroke, but a rapid and sensitive blood test for ischemic stroke does not exist. This study tested whether a panel of biomarkers might be useful in the diagnosis of acute ischemic stroke. Consecutive patients with suspected stroke presenting to the emergency department of a university hospital in Korea were enrolled. Plasma specimens were assayed for brain natriuretic peptide, D-dimer, matrix metalloproteinase-9, S100β, and a proprietary composite multimarker index (MMX). There were 139 patients in this study, 89 of whom were diagnosed with acute ischemic stroke, 11 with acute cerebral hemorrhage, and 39 with other brain disorders. The MMX value was significantly higher in the patients with acute ischemic stroke in comparison to 57 healthy controls (p <0.001), but there was no significant difference between the MMX value in patients with acute ischemic stroke vs those with acute cerebral hemorrhage (p = 0.884). The discriminatory capacity of MMX was modest, with an area under the receiver-operating-characteristic curve of 0.714 for acute stroke. Ischemic stroke was not diagnosed by any of the biochemical markers individually. Although the data suggest that MMX may be helpful to diagnose an acute stroke, it does not discriminate between acute ischemic stroke and acute hemorrhagic stroke.

  11. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells

    PubMed Central

    Jin, Rong; Yang, Guojun; Li, Guohong

    2010-01-01

    Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Experimentally and clinically, the brain responds to ischemic injury with an acute and prolonged inflammatory process, characterized by rapid activation of resident cells (mainly microglia), production of proinflammatory mediators, and infiltration of various types of inflammatory cells (including neutrophils, different subtypes of T cells, monocyte/macrophages, and other cells) into the ischemic brain tissue. These cellular events collaboratively contribute to ischemic brain injury. Despite intense investigation, there are still numerous controversies concerning the time course of the recruitment of inflammatory cells in the brain and their pathogenic roles in ischemic brain injury. In this review, we provide an overview of the time-dependent recruitment of different inflammatory cells following focal cerebral I/R. We discuss how these cells contribute to ischemic brain injury and highlight certain recent findings and currently unanswered questions about inflammatory cells in the pathophysiology of ischemic stroke. PMID:20130219

  12. Screening for coagulation disorders in patients with ischemic stroke.

    PubMed

    de Lau, Lonneke Ml; Leebeek, Frank Wg; de Maat, Moniek Pm; Koudstaal, Peter J; Dippel, Diederik Wj

    2010-08-01

    The role of coagulation disorders in the pathogenesis of (recurrent) ischemic stroke is uncertain. Therefore, the clinical utility of screening patients with ischemic stroke for these conditions and the therapeutic implications of a detected coagulation disorder in a patient who experienced ischemic stroke are uncertain. We reviewed the currently available data on the relationship between various inherited and acquired coagulation abnormalities (factor V Leiden and prothrombin G20210A mutations, deficiencies of protein C, protein S and anti-thrombin, hyperhomocysteinemia, the antiphospholipid syndrome and increased levels of fibrinogen) and ischemic stroke. Based on the existing evidence we discuss the usefulness of screening stroke patients for prothrombotic conditions and current recommendations regarding the optimal management of ischemic stroke patients in whom a coagulation disorder is found.

  13. Metabolic Prosthesis for Oxygenation of Ischemic Tissue

    SciTech Connect

    Greenbaum, Elias

    2009-01-01

    This communication discloses new ideas and preliminary results on the development of a "metabolic prosthesis" for local oxygenation of ischemic tissue under physiological neutral conditions. We report for the first time the selective electrolysis of physiological saline by repetitively pulsed charge-limited electrolysis for the production of oxygen and suppression of free chlorine. For example, using 800 A amplitude current pulses and <200 sec pulse durations, we demonstrated prompt oxygen production and delayed chlorine production at the surface of a shiny 0.85 mm diameter spherical platinum electrode. The data, interpreted in terms of the ionic structure of the electric double layer, suggest a strategy for in situ production of metabolic oxygen via a new class of "smart" prosthetic implants for dealing with ischemic disease such as diabetic retinopathy. We also present data indicating that drift of the local pH of the oxygenated environment can be held constant using a feedback-controlled three electrode electrolysis system that chooses anode and cathode pair based on pH data provided by local microsensors. The work is discussed in the context of diabetic retinopathy since surgical techniques for multielectrode prosthetic implants aimed at retinal degenerative diseases have been developed.

  14. Creatine kinase in ischemic and inflammatory disorders.

    PubMed

    Kitzenberg, David; Colgan, Sean P; Glover, Louise E

    2016-12-01

    The creatine/phosphocreatine pathway plays a conserved and central role in energy metabolism. Compartmentalization of specific creatine kinase enzymes permits buffering of local high energy phosphates in a thermodynamically favorable manner, enabling both rapid energy storage and energy transfer within the cell. Augmentation of this metabolic pathway by nutritional creatine supplementation has been shown to elicit beneficial effects in a number of diverse pathologies, particularly those that incur tissue ischemia, hypoxia or oxidative stress. In these settings, creatine and phosphocreatine prevent depletion of intracellular ATP and internal acidification, enhance post-ischemic recovery of protein synthesis and promote free radical scavenging and stabilization of cellular membranes. The creatine kinase energy system is itself further regulated by hypoxic signaling, highlighting the existence of endogenous mechanisms in mammals that can enhance creatine metabolism during oxygen deprivation to promote tissue resolution and homeostasis. Here, we review recent insights into the creatine kinase pathway, and provide rationale for dietary creatine supplementation in human ischemic and inflammatory pathologies.

  15. SPECT and PET in ischemic heart failure.

    PubMed

    Angelidis, George; Giamouzis, Gregory; Karagiannis, Georgios; Butler, Javed; Tsougos, Ioannis; Valotassiou, Varvara; Giannakoulas, George; Dimakopoulos, Nikolaos; Xanthopoulos, Andrew; Skoularigis, John; Triposkiadis, Filippos; Georgoulias, Panagiotis

    2017-02-02

    Heart failure is a common clinical syndrome associated with significant morbidity and mortality worldwide. Ischemic heart disease is the leading cause of heart failure, at least in the industrialized countries. Proper diagnosis of the syndrome and management of patients with heart failure require anatomical and functional information obtained through various imaging modalities. Nuclear cardiology techniques play a main role in the evaluation of heart failure. Myocardial single photon emission computed tomography (SPECT) with thallium-201 or technetium-99 m labelled tracers offer valuable data regarding ventricular function, myocardial perfusion, viability, and intraventricular synchronism. Moreover, positron emission tomography (PET) permits accurate evaluation of myocardial perfusion, metabolism, and viability, providing high-quality images and the ability of quantitative analysis. As these imaging techniques assess different parameters of cardiac structure and function, variations of sensitivity and specificity have been reported among them. In addition, the role of SPECT and PET guided therapy remains controversial. In this comprehensive review, we address these controversies and report the advances in patient's investigation with SPECT and PET in ischemic heart failure. Furthermore, we present the innovations in technology that are expected to strengthen the role of nuclear cardiology modalities in the investigation of heart failure.

  16. Psoriasis and ischemic coronary artery disease.

    PubMed

    Mahiques-Santos, L; Soriano-Navarro, C J; Perez-Pastor, G; Tomas-Cabedo, G; Pitarch-Bort, G; Valcuende-Cavero, F

    2015-03-01

    Psoriasis is a chronic inflammatory disease associated with an increased risk of ischemic coronary artery disease (CAD) in some populations. We aimed to determine the association between these 2 diseases in our geographic area. We performed a cross-sectional study of patient records between 2005 and 2012 in the database (Abucacis, Datamart) that contains all medical case histories in the province of Castellón, Spain. Patients diagnosed with psoriasis were compared with a control group of patients diagnosed with melanocytic nevus. The prevalence of CAD and the presence or absence of the main cardiovascular risk factors were analyzed in each group. A total of 9181 patients with psoriasis and 21925 with melanocytic nevus were studied. Univariate logistic regression analysis showed that CAD was significantly associated with psoriasis, age (in years), sex, hypertension, diabetes mellitus, dyslipidemia, and obesity (P<.05). On adjustment for age, sex, and the other cardiovascular risk factors, multivariate regression analysis established that psoriasis was independently associated with CAD (P<.029). Our findings in a large sample of patients in a Mediterranean area support the hypothesis that patients in this population have an increased risk of ischemic CAD. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

  17. Genistein: A Boon for Mitigating Ischemic Stroke.

    PubMed

    Nabavi, Seyed Fazel; Daglia, Maria; Tundis, Rosa; Loizzo, Monica Rosa; Sobarzo-Sanchez, Eduardo; Orhan, Ilkay Erdogan; Nabavi, Seyed Mohammad

    2015-01-01

    In last decades, diet and dietary components have been regarded as important strategies to prevent the development or mitigate numerous chronic diseases, including inflammation, cardiovascular pathologies, cancer, etc. One of the most common dietary components of Asian population is soy. A plethora of research shows the promising effect of soy soy-based foodstuffs and genistein, which is one of the predominant isoflavone compounds, in the prevention and mitigation of stroke. Growing evidence shows that genistein, which is a selective estrogen receptor modulator, mitigates ischemic stroke-induced damages through the modification of oxidative stress and molecular pathways. The promising pharmacological role of genistein is attributed to its ability to suppress nuclear factor (NF)-kappa B and Akt signaling pathway, direct antioxidant action, and targeting estrogen and androgen-mediated molecular pathways which help to mitigate stroke damages and prolong cell survival. In this work, we systematically review the current reports on the therapeutic role of genistein against ischemic stroke and its molecular mechanism of actions.

  18. Green space and mortality following ischemic stroke.

    PubMed

    Wilker, Elissa H; Wu, Chih-Da; McNeely, Eileen; Mostofsky, Elizabeth; Spengler, John; Wellenius, Gregory A; Mittleman, Murray A

    2014-08-01

    Residential proximity to green space has been associated with physical and mental health benefits, but whether green space is associated with post-stroke survival has not been studied. Patients ≥ 21 years of age admitted to the Beth Israel Deaconess Medical Center (BIDMC) between 1999 and 2008 with acute ischemic stroke were identified. Demographics, presenting symptoms, medical history and imaging results were abstracted from medical records at the time of hospitalization for stroke onset. Addresses were linked to average Normalized Difference Vegetation Index, distance to roadways with more than 10,000 cars/day, and US census block group. Deaths were identified through June 2012 using the Social Security Death Index. There were 929 deaths among 1645 patients with complete data (median follow up: 5 years). In multivariable Cox models adjusted for indicators of medical history, demographic and socioeconomic factors, the hazard ratio for patients living in locations in the highest quartile of green space compared to the lowest quartile was 0.78 (95% Confidence Interval: 0.63-0.97) (p-trend = 0.009). This association remained statistically significant after adjustment for residential proximity to a high traffic road. Residential proximity to green space is associated with higher survival rates after ischemic stroke in multivariable adjusted models. Further work is necessary to elucidate the underlying mechanisms for this association, and to better understand the exposure-response relationships and susceptibility factors that may contribute to higher mortality in low green space areas. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Childhood ischemic stroke in a nonurban population.

    PubMed

    Bowen, Michael D; Burak, Christopher R; Barron, Todd F

    2005-03-01

    A 10-year, retrospective review of the etiology, outcome, and complications of ischemic stroke in children from a nonurban population was conducted. Twenty-seven children were identified (14 boys, 13 girls), ages 1.25 to 17 years (mean 7.7 years). Etiologies included undetermined (22%), arterial dissection (19%), coagulopathy (15%), embolism (15%), moyamoya disease (11%), sickle cell disease (11%), isolated angiitis of the central nervous system or vasculitis (11%), or other known source (11%; two fibromuscular dysplasia, one L-asparaginase). More than one risk factor was present in five children. Seventeen (65%) children were anticoagulated, with no adverse events occurring. Nine children were anticoagulated initially with low-molecular-weight heparin. Other treatments included corticosteroids; physical, occupational, and speech therapy; and anticonvulsants for concomitant seizures. Follow-up ranged from 3 to 60 months (mean 17 months) and was as follows: 6 (22%) were normal, 9 (33%) had mild impairment, and 12 (44%) had moderate to severe deficits. There were no deaths. Neurologic complications included seizure (two), behavioral problems (two), and hemorrhagic conversion (one). In this population, the outcome from ischemic stroke was similar to that of other studies, with the majority of children demonstrating persistent neurologic deficits. Etiology could be determined for the majority of patients, with 19% having more than one risk factor.

  20. Complement in the Homeostatic and Ischemic Brain

    PubMed Central

    Alawieh, Ali; Elvington, Andrew; Tomlinson, Stephen

    2015-01-01

    The complement system is a component of the immune system involved in both recognition and response to pathogens, and it is implicated in an increasing number of homeostatic and disease processes. It is well documented that reperfusion of ischemic tissue results in complement activation and an inflammatory response that causes post-reperfusion injury. This occurs following cerebral ischemia and reperfusion and triggers secondary damage that extends beyond the initial infarcted area, an outcome that has rationalized the use of complement inhibitors as candidate therapeutics after stroke. In the central nervous system, however, recent studies have revealed that complement also has essential roles in synaptic pruning, neurogenesis, and neuronal migration. In the context of recovery after stroke, these apparent divergent functions of complement may account for findings that the protective effect of complement inhibition in the acute phase after stroke is not always maintained in the subacute and chronic phases. The development of effective stroke therapies based on modulation of the complement system will require a detailed understanding of complement-dependent processes in both early neurodegenerative events and delayed neuro-reparatory processes. Here, we review the role of complement in normal brain physiology, the events initiating complement activation after cerebral ischemia-reperfusion injury, and the contribution of complement to both injury and recovery. We also discuss how the design of future experiments may better characterize the dual role of complement in recovery after ischemic stroke. PMID:26322048

  1. Evolving Treatments for Acute Ischemic Stroke.

    PubMed

    Zerna, Charlotte; Hegedus, Janka; Hill, Michael D

    2016-04-29

    The purpose of this article is to review advances in stroke treatment in the hyperacute period. With recent evolutions of technology in the fields of imaging, thrombectomy devices, and emergency room workflow management, as well as improvement in statistical methods and study design, there have been ground breaking changes in the treatment of acute ischemic stroke. We describe how stroke presents as a clinical syndrome and how imaging as the most important biomarker will help differentiate between stroke subtypes and treatment eligibility. The evolution of hyperacute treatment has led to the current standard of care: intravenous thrombolysis with tissue-type plasminogen activator and endovascular treatment for proximal vessel occlusion in the anterior cerebral circulation. All patients with acute ischemic stroke are in need of hyperacute secondary prevention because the risk of recurrence is highest closest to the index event. The dominant themes of modern stroke care are the use of neurovascular imaging and speed of diagnosis and treatment. © 2016 American Heart Association, Inc.

  2. Advanced imaging in acute ischemic stroke.

    PubMed

    Kilburg, Craig; Scott McNally, J; de Havenon, Adam; Taussky, Philipp; Kalani, M Yashar S; Park, Min S

    2017-04-01

    The evaluation and management of acute ischemic stroke has primarily relied on the use of conventional CT and MRI techniques as well as lumen imaging sequences such as CT angiography (CTA) and MR angiography (MRA). Several newer or less-established imaging modalities, including vessel wall MRI, transcranial Doppler ultrasonography, and 4D CTA and MRA, are being developed to complement conventional CT and MRI techniques. Vessel wall MRI provides high-resolution analysis of both extracranial and intracranial vasculature to help identify previously occult lesions or characteristics of lesions that may portend a worse natural history. Transcranial Doppler ultrasonography can be used in the acute setting as a minimally invasive way of identifying large vessel occlusions or monitoring the response to stroke treatment. It can also be used to assist in the workup for cryptogenic stroke or to diagnose a patent foramen ovale. Four-dimensional CTA and MRA provide a less invasive alternative to digital subtraction angiography to determine the extent of the clot burden and the degree of collateral blood flow in large vessel occlusions. Along with technological advances, these new imaging modalities are improving the diagnosis, workup, and management of acute ischemic stroke- roles that will continue to expand in the future.

  3. The Desmoteplase in Acute Ischemic Stroke (DIAS) clinical trial program.

    PubMed

    von Kummer, Rüdiger; Albers, Gregory W; Mori, Etsuro

    2012-10-01

    Desmoteplase is a novel, highly fibrin-specific thrombolytic agent in phase III of clinical development. In comparison to alteplase, it has high fibrin selectivity, is associated with minimal or no neurotoxicity, and has no apparent negative effect on the blood-brain barrier. The safety and efficacy of desmoteplase is being studied in the Desmoteplase in Acute Ischemic Stroke clinical trial program. Three studies (Dose Escalation Study of Desmoteplase in Acute Ischemic Stroke, Desmoteplase in Acute Ischemic Stroke, and Desmoteplase in Acute Ischemic Stroke-2) have been completed, two large randomized, double-blind, placebo-controlled, phase III trials are ongoing at >200 sites worldwide (Desmoteplase in Acute Ischemic Stroke-3 and Desmoteplase in Acute Ischemic Stroke-4, n = 800; DIAS-3 and DIAS-4), and a randomized, double-blind, placebo-controlled, dose-escalation phase II trial is ongoing in Japan (Desmoteplase in Acute Ischemic Stroke-Japan, n = 48; DIAS-J). The objective of DIAS-3 and DIAS-4 is to evaluate the safety and efficacy of a single IV bolus injection of 90 μg/kg desmoteplase given three- to nine-hours after onset of ischemic stroke (National Institutes of Health Stroke Scale 4-24, age 18-85 years). The objective of DIAS-J is to evaluate the safety and tolerability of desmoteplase 70 and 90 μg/kg three- to nine-hours after ischemic stroke onset in Japanese patients. Patients are included with occlusion or high-grade stenosis (thrombolysis in myocardial infarction 0-1) in proximal cerebral arteries on magnetic resonance or computed tomography angiography but excluded with extended ischemic edema on computed tomography or diffusion-weighted imaging. Desmoteplase is the only thrombolytic agent in late-stage development for acute ischemic stroke that is now tested in patients with proven stroke pathology. The results of the Desmoteplase in Acute Ischemic Stroke clinical trial program will show whether patients with major artery occlusions

  4. Surgical treatment of moderate ischemic mitral regurgitation.

    PubMed

    Smith, Peter K; Puskas, John D; Ascheim, Deborah D; Voisine, Pierre; Gelijns, Annetine C; Moskowitz, Alan J; Hung, Judy W; Parides, Michael K; Ailawadi, Gorav; Perrault, Louis P; Acker, Michael A; Argenziano, Michael; Thourani, Vinod; Gammie, James S; Miller, Marissa A; Pagé, Pierre; Overbey, Jessica R; Bagiella, Emilia; Dagenais, François; Blackstone, Eugene H; Kron, Irving L; Goldstein, Daniel J; Rose, Eric A; Moquete, Ellen G; Jeffries, Neal; Gardner, Timothy J; O'Gara, Patrick T; Alexander, John H; Michler, Robert E

    2014-12-04

    Ischemic mitral regurgitation is associated with increased mortality and morbidity. For surgical patients with moderate regurgitation, the benefits of adding mitral-valve repair to coronary-artery bypass grafting (CABG) are uncertain. We randomly assigned 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus mitral-valve repair (combined procedure). The primary end point was the left ventricular end-systolic volume index (LVESVI), a measure of left ventricular remodeling, at 1 year. This end point was assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized as the lowest LVESVI rank. At 1 year, the mean LVESVI among surviving patients was 46.1±22.4 ml per square meter of body-surface area in the CABG-alone group and 49.6±31.5 ml per square meter in the combined-procedure group (mean change from baseline, -9.4 and -9.3 ml per square meter, respectively). The rate of death was 6.7% in the combined-procedure group and 7.3% in the CABG-alone group (hazard ratio with mitral-valve repair, 0.90; 95% confidence interval, 0.38 to 2.12; P=0.81). The rank-based assessment of LVESVI at 1 year (incorporating deaths) showed no significant between-group difference (z score, 0.50; P=0.61). The addition of mitral-valve repair was associated with a longer bypass time (P<0.001), a longer hospital stay after surgery (P=0.002), and more neurologic events (P=0.03). Moderate or severe mitral regurgitation was less common in the combined-procedure group than in the CABG-alone group (11.2% vs. 31.0%, P<0.001). There were no significant between-group differences in major adverse cardiac or cerebrovascular events, deaths, readmissions, functional status, or quality of life at 1 year. In patients with moderate ischemic mitral regurgitation, the addition of mitral-valve repair to CABG did not result in a higher degree of left ventricular reverse remodeling. Mitral-valve repair was associated with a reduced prevalence of moderate or

  5. Transient ischemic attack: an evidence-based update.

    PubMed

    Siket, Matthew S; Edlow, Jonathan

    2013-01-01

    Transient ischemic attack represents a medical emergency and warns of an impending stroke in roughly one-third of patients who experience it. The risk of stroke is highest in the first 48 hours following a transient ischemic attack, and the initial evaluation in the emergency department is the best opportunity to identify those at highest risk of stroke recurrence. The focus should be on differentiating transient ischemic attack from stroke and common mimics. Accurate diagnosis is achieved by obtaining a history of abrupt onset of negative symptoms of ischemic origin fitting a vascular territory, accompanied by a normal examination and the absence of neuroimaging evidence of infarction. Transient ischemic attacks rarely last longer than 1 hour, and the classic 24-hour time-based definition is no longer relevant. Once the diagnosis has been made, clinical risk criteria may augment imaging findings to identify patients at highest and lowest risk of early recurrence. Early etiologic evaluation, including neurovascular and cardiac investigations, allows for catered secondary prevention strategies. Specialized transient ischemic attack clinics and emergency department observation units are safe and efficient alternatives to hospital admission for many transient ischemic attack patients.

  6. Plasma desmoplakin I biomarker of vascular recurrence after ischemic stroke.

    PubMed

    López-Farré, Antonio J; Zamorano-León, José J; Segura, Antonio; Mateos-Cáceres, Petra J; Modrego, Javier; Rodríguez-Sierra, Pablo; Calatrava, Laura; Tamargo, Juan; Macaya, Carlos

    2012-04-01

    Stroke patients have a high risk of vascular recurrence. Biomarkers related to vascular recurrence, however, remain to be identified. The aim of the study was to identify, through proteomic analysis, plasma biomarkers associated with vascular recurrence within one year after the first ischemic stroke. This is a substudy (n = 134) of a large prospective multicenter study of post-stroke patients with an ischemic stroke. Plasma samples were obtained at inclusion. Among the identified proteins, only plasma levels of desmoplakin I were associated with protection against a new vascular event (Odds ratio: 0.64; 95% CI: 0.46-0.89; p = 0.009) after adjustment for hypercholesterolemia, statins and previous atherothrombotic stroke subtype. A greater number of patients without vascular recurrence had been treated with statins within three months of the recent ischemic stroke. Only patients who had been taking statins for 3 months after the ischemic stroke and did not suffer vascular recurrence over a follow-up year, have higher levels of desmoplakin I at the time of inclusion (Odds ratio 0.49; 95% CI: 0.28-0.86; p = 0.013). Increased desmoplakin I levels, determined within 1-3 months of the first ischemic stroke, could be a biomarker for statin responsiveness against a new vascular event in post-ischemic stroke patients taking statins early (1-3 months) after the ischemic stroke.

  7. Central Nervous System Agents for Ischemic Stroke: Neuroprotection Mechanisms

    PubMed Central

    Pandya, Rachna S.; Mao, Lijuan; Zhou, Hua; Zhou, Shuanhu; Zeng, Jiang; Popp, A. John; Wang, Xin

    2011-01-01

    Stroke is the third leading cause of mortality and disability in the United States. Ischemic stroke constitutes 85% of all stroke cases. However, no effective treatment has been found to prevent damage to the brain in such cases except tissue plasminogen activator with narrow therapeutic window, and there is an unmet need to develop therapeutics for neuroprotection from ischemic stroke. Studies have shown that mechanisms including apoptosis, necrosis, inflammation, immune modulation, and oxidative stress and mediators such as excitatory amino acids, nitric oxide, inflammatory mediators, neurotransmitters, reactive oxygen species, and withdrawal of trophic factors may lead to the development of the ischemic cascade. Hence, it is essential to develop neuroprotective agents targeting either the mechanisms or the mediators leading to development of ischemic stroke. This review focuses on central nervous system agents targeting these biochemical pathways and mediators of ischemic stroke, mainly those that counteract apoptosis, inflammation, and oxidation, and well as glutamate inhibitors which have been shown to provide neuroprotection in experimental animals. All these agents have been shown to improve neurological outcome after ischemic insult in experimental animals in vivo, organotypic brain slice/acute slice ex vivo, and cell cultures in vitro and may therefore aid in preventing long-term morbidity and mortality associated with ischemic stroke. PMID:21521165

  8. PTEN degradation after ischemic stroke: a double-edged sword.

    PubMed

    Li, W; Huang, R; Chen, Z; Yan, L-J; Simpkins, J W; Yang, S-H

    2014-08-22

    Tumor suppressor phosphatase and tensin homolog (PTEN) is highly expressed in neurons and PTEN inhibition has been reported to be neuroprotective against ischemic stroke in experimental models. On the other hand, PTEN deletion has been shown to lead to cognitive impairment. In the current study, we examined the expression and functions of PTEN in an ischemic stroke rodent model. We found rapid S-nitrosylation and degradation of PTEN after cerebral ischemia/reperfusion injury. PTEN degradation leads to activation of Akt. PTEN partial deletion or PTEN inhibition increased the expression of GABAA receptor (GABAAR) γ2 subunit and enhanced GABAA receptor current. After cerebral ischemia, increased expression of GABAAR γ2 subunit was observed in the ischemia region and the penumbra area. We also observed PTEN loss in astrocytes after cerebral ischemia. Astrocytic PTEN partial knockout increased astrocyte activation and exacerbated ischemic damage. We speculated that ischemic stroke induced neuronal PTEN degradation, hence enhanced GABAA receptor-medicated neuronal activity inhibition which could attenuate excitotoxicity and provide neuroprotection during the acute phase after stroke, while inhibiting long-term functional recovery and contributing to vascular cognitive impairment after stroke. On the other hand, ischemic stroke induced astrocytic PTEN loss and enhanced ischemic damage and astrogliosis. Taken together, our study indicates that ischemic stroke induces rapid PTEN degradation in both neurons and astrocytes which play both protective and detrimental action in a spatiotemporal- and cell-type-dependent manner. Our study provides critical insight for targeting PTEN signaling pathway for stroke treatment.

  9. Is opium addiction a risk factor for ischemic heart disease and ischemic stroke?

    PubMed

    Rezvani, Mohammad Reza; Ghandehari, Kavian

    2012-10-01

    The main source of studies about effects of opium consumption on heart and brain attacks originates from Iran Therefore the aim of the present study was to assess opium addiction as a probable influencing factor for ischemic heart disease and ischemic stroke. A cross-sectional study was carried out in two Cardiology and Neurology clinics in Eastern Iran in 2011. Diagnosis of Ischemic Heart Disease (IHD) and Ischemic Stroke (IS) was made by Cardiologist and Stroke Neurologist respectively. The influence of gender, hypertension, diabetes, hyperlipidemia, cigarette smoking, oral and inhaled opium consumption on distribution of IHD and IS were evaluated. Five hundred fifty eight patients (307 females, 251 males) with mean age 56.2 years enrolled the study. On adjusted odds ratios of our whole 558 patients, only hypertension and diabetes had a significant influence on occurrence of IHD; (P = 0.000 and P = 0.000) respectively. Oral and inhaled routes of opium addiction did not have a significant effect on occurrence of IHD; [OR = 1.172, 95% CI = 0.624-2.203, P = 0.621] and [OR = 1.820, 95% CI = 0.811-4.085, P = 0.147] respectively. Hypertension and diabetes were significant risk factors of IS in our 558 patients at multivariate analysis; (P = 0.000, P = 0.020). Oral opium addiction was as significant protective factor of IS in our study group; OR = 0.211, 95% CI = 0.079-0.564, P = 0.002, while inhaled opium addiction did not have a significant effect on occurrence of IS in our patients at; OR = 1.760, 95% CI = 0.760-4.076, P = 0.187. Oral opium consumption is a protective factor of IS but not IHD. Inhaled opium addiction does not have a significant influence on occurrence of IS and IHD.

  10. Transferring Xenogenic Mitochondria Provides Neural Protection Against Ischemic Stress in Ischemic Rat Brains.

    PubMed

    Huang, Po-Jui; Kuo, Chi-Chung; Lee, Hsiu-Chin; Shen, Ching-I; Cheng, Fu-Chou; Wu, Shih-Fang; Chang, Jui-Chih; Pan, Hung-Chuan; Lin, Shinn-Zong; Liu, Chin-San; Su, Hong-Lin

    2016-01-01

    Transferring exogenous mitochondria has therapeutic effects on damaged heart, liver, and lung tissues. Whether this protective effect requires the symbiosis of exogenous mitochondria in host cells remains unknown. Here xenogenic mitochondria derived from a hamster cell line were applied to ischemic rat brains and rat primary cortical neurons. Isolated hamster mitochondria, either through local intracerebral or systemic intra-arterial injection, significantly restored the motor performance of brain-ischemic rats. The brain infarct area and neuronal cell death were both attenuated by the exogenous mitochondria. Although internalized mitochondria could be observed in neurons and astrocytes, the low efficacy of mitochondrial internalization could not completely account for the high rate of rescue of the treated neural cells. We further illustrated that disrupting electron transport or ATPase synthase in mitochondria significantly attenuated the protective effect, suggesting that intact respiratory activity is essential for the mitochondrial potency on neural protection. These results emphasize that nonsymbiotic extracellular mitochondria can provide an effective cell defense against acute injurious ischemic stress in the central nervous system.

  11. Cerebral Microbleeds and Cognitive Function in Ischemic Stroke or Transient Ischemic Attack Patients.

    PubMed

    Wang, Zhaolu; Wong, Adrian; Liu, Wenyan; Yang, Jie; Chu, Winnie C W; Au, Lisa; Lau, Alexander; Chan, Anne; Xiong, Yunyun; Soo, Yannie; Leung, Thomas; Wong, Lawrence K S; Mok, Vincent C T

    2015-01-01

    We explored the association between cerebral microbleeds (CMBs) and cognitive impairment in patients with ischemic stroke/transient ischemic attack (TIA). A total of 488 ischemic stroke/TIA patients received magnetic resonance imaging. Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive function and cognitive domains. The association of CMB quantity with cognitive function and the impact of CMB locations (strictly lobar, strictly deep, and mixed regions) on cognitive impairment were examined in regression models with adjustments for confounders. A total of 113 subjects (23.2%) had ≥1 CMB. Strictly lobar, strictly deep, and mixed CMBs were identified in 36, 40, and 37 patients, respectively. The presence of ≥5 CMBs or strictly deep CMBs was associated with the MoCA total score (p = 0.007 and 0.020, respectively). Of all MoCA domains tested, a lower score in the attention domain was related to the presence of ≥5 CMBs (p = 0.014) and strictly deep CMBs (p = 0.028). CMBs were associated with cognitive dysfunction in stroke/TIA patients, especially in the attention domain. This association was mainly driven by CMBs in the deep region, underlining the role of hypertensive microangiopathy in stroke-related cognitive impairment.

  12. Prevention of the collapse of pial collaterals by remote ischemic perconditioning during acute ischemic stroke.

    PubMed

    Ma, Junqiang; Ma, Yonglie; Dong, Bin; Bandet, Mischa V; Shuaib, Ashfaq; Winship, Ian R

    2017-08-01

    Collateral circulation is a key variable determining prognosis and response to recanalization therapy during acute ischemic stroke. Remote ischemic perconditioning (RIPerC) involves inducing peripheral ischemia (typically in the limbs) during stroke and may reduce perfusion deficits and brain damage due to cerebral ischemia. In this study, we directly investigated pial collateral flow augmentation due to RIPerC during distal middle cerebral artery occlusion (MCAo) in rats. Blood flow through pial collaterals between the anterior cerebral artery (ACA) and the MCA was assessed in male Sprague Dawley rats using in vivo laser speckle contrast imaging (LSCI) and two photon laser scanning microscopy (TPLSM) during distal MCAo. LSCI and TPLSM revealed that RIPerC augmented collateral flow into distal MCA segments. Notably, while control rats exhibited an initial dilation followed by a progressive narrowing of pial arterioles 60 to 150-min post-MCAo (constricting to 80-90% of post-MCAo peak diameter), this constriction was prevented or reversed by RIPerC (such that vessel diameters increased to 105-110% of post-MCAo, pre-RIPerC diameter). RIPerC significantly reduced early ischemic damage measured 6 h after stroke onset. Thus, prevention of collateral collapse via RIPerC is neuroprotective and may facilitate other protective or recanalization therapies by improving blood flow in penumbral tissue.

  13. Severe ischemic colitis following olanzapine use - A case report.

    PubMed

    Fernandes, Samuel R; Alves, Rosa; Araújo Correia, Luís; Rita Gonçalves, Ana; Malaquias, João; Oliveira, Emilia; Velosa, José

    2016-09-01

    Ischemic colitis is the most common subtype of intestinal ischemia usually resulting from vasospasm, vessel occlusion or mesenteric hypoperfusion. Neuroleptics have seldom been linked to ischemic colitis by blocking peripheral anticholinergic and antiserotonergic receptors inducing severe gastrointestinal paresis. We report a young patient with severe ischemic colitis requiring surgery due to necrosis of the bowel. After exclusion of other potential causes, olanzapine was admitted as the cause of ischemia. Clinicians should be aware of how to recognize and treat the potentially life-threatening effects of neuroleptics.

  14. Neuroprotective Effects of Stem Cells in Ischemic Stroke

    PubMed Central

    Xu, Weilin; Zheng, Jingwei; Gao, Liansheng; Li, Tao

    2017-01-01

    Ischemic stroke, the most common subtype of stroke, has been one of the leading causes of mobility and mortality worldwide. However, it is still lacking of efficient agents. Stem cell therapy, with its vigorous advantages, has attracted researchers around the world. Numerous experimental researches in animal models of stroke have demonstrated the promising efficacy in treating ischemic stroke. The underlying mechanism involved antiapoptosis, anti-inflammation, promotion of angiogenesis and neurogenesis, formation of new neural cells and neuronal circuitry, antioxidation, and blood-brain barrier (BBB) protection. This review would focus on the types and neuroprotective actions of stem cells and its potential mechanisms for ischemic stroke. PMID:28757878

  15. Acute Stroke and Transient Ischemic Attack in the Outpatient Clinic.

    PubMed

    Cruz-Flores, Salvador

    2017-05-01

    Ischemic stroke is cause of substantial death and disability in the United States. Transient ischemic attack, a precursor to ischemic stroke, conveys a high risk of recurrent stroke within 90 days from event. These conditions are highly preventable and treatable. The cause is heterogenous and includes atherothrombosis, cardioembolism, lacunar disease, or cryptogenic, and some uncommon causes, such as arterial dissection and prothrombotic states. The emergent evaluation includes establishing time of onset, vital signs, glucose level, and severity of the deficit. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Remote ischemic preconditioning enhances fracture healing

    PubMed Central

    Çatma, Mehmet Faruk; Şeşen, Hakan; Aydın, Aytekin; Ünlü, Serhan; Demirkale, İsmail; Altay, Murat

    2015-01-01

    Purpose We hypothesized that RIP accelerates fracture healing. Methods Rats (n = 48) were used for the technique of ischemic preconditioning involved applying 35 min of intermittent pneumatic tourniquet for 7 cycles of 5 min each to the fractured hind limb. Results We observed greater callus maturity in RIP group at first week after fracture when compared to controls (p < 0,0001). The serum MDA levels demonstrated statistically lower values at the RIP group at the first week after fracture; however, there were not significant differences at 3rd and 5th weeks (p = 0.0001, p = 0.725, p = 0.271, respectively). Conclusions Greater callus maturity was obtained in RIP group. PMID:26566314

  17. Spinal cord infarction mimicking ischemic heart disease.

    PubMed

    Lee, Dae Won; Choi, Yoon Hee

    2017-06-01

    Spinal cord infarction is a rare condition and is easily misdiagnosed owing to its initial non-specific manifestation. We report a case of a 77-year-old man who presented with chest pain and upper back pain initially, and was misdiagnosed with a myocardial infarction. Four hours after admission, he complained of numbness in his entire left leg below the knee, with rapid deterioration of neurological symptoms. After 9 hours, loss of sensation progressed up to the T4 dermatome, strength of both lower extremities deteriorated to grade 0, and decrease in anal tone and deep tendon reflex was observed. Initial magnetic resonance imaging findings were normal; however, a signal change occurred 3 days after symptom onset. When patients present with acute chest pain and neurologic symptoms, the possibility of ischemic cardiac disease as well as any neurological manifestations must be investigated. Emergency physicians must remember the value of serial physical examinations.

  18. Use of nitrates in ischemic heart disease.

    PubMed

    Giuseppe, Cocco; Paul, Jerie; Hans-Ulrich, Iselin

    2015-01-01

    Short-acting nitrates are beneficial in acute myocardial ischemia. However, many unresolved questions remain about the use of long-acting nitrates in stable ischemic heart disease. The use of long-acting nitrates is weakened by the development of endothelial dysfunction and tolerance. Also, we currently ignore whether lower doses of transdermal nitroglycerin would be better than those presently used. Multivariate analysis data from large nonrandomized studies suggested that long-acting nitrates increase the incidence of acute coronary syndromes, while data from another multivariate study indicate that they have positive effects. Because of methodological differences and open questions, the two studies cannot be compared. A study in Japanese patients with vasospastic angina has shown that, when compared with calcium antagonists, long-acting nitrates do not improve long-term prognosis and that the risk for cardiac adverse events increases with the combined therapy. We have many unanswered questions.

  19. [Secondary prevention of ischemic non cardioembolic stroke].

    PubMed

    Armario, Pedro; Pinto, Xavier; Soler, Cristina; Cardona, Pere

    2015-01-01

    Stroke patients are at high risk for recurrence or new occurrence of other cardiovascular events or cardiovascular mortality. It is estimated that a high percentage of non-cardioembolic ischemic stroke can be prevented by a suitable modification of lifestyle (diet and exercise), reducing blood pressure (BP) with antihypertensive medication, platelet aggregation inhibitors, statins and high intake reducing consumption of. Unfortunately the degree of control of the different risk factors in secondary prevention of stroke is low. The clinical practice guidelines show clear recommendations with corresponding levels of evidence, but only if implemented in a general way they will get a better primary and secondary stroke prevention. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  20. Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy

    PubMed Central

    Dixon, Brandon J.; Reis, Cesar; Ho, Wing Mann; Tang, Jiping; Zhang, John H.

    2015-01-01

    Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. We will identify understudied targets after HIE, as well as neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-beta, stem cell transplantation. This review will also discuss some of the most recent trials being conducted in the clinical setting and evaluate what directions are needed in the future. PMID:26389893

  1. [Recurrent ischemic strokes revealing Lyme meningovascularitis].

    PubMed

    Sparsa, L; Blanc, F; Lauer, V; Cretin, B; Marescaux, C; Wolff, V

    2009-03-01

    Infectious vascularitis is an unusual cause of ischemic stroke (IS). We report a case of Lyme meningovascularitis complicated with multiple IS. A 64-year-old man, without any cardiovascular risk factor, was admitted for a right hemiparesia with a left thalamic hypodensity on the initial cerebral CT scan. No cause for this presumed IS could be identified. Later, the patient developed cognitive impairment and a bilateral cerebellar syndrome. Multiple infarcts and multiple intracranial stenosis were seen on cerebral MRI with magnetic resonance angiography (MRA). Cerebrospinal fluid tests showed meningitis and positive Lyme serology with an intrathecal specific anti-Borrelia antibody index. Antibiotic treatment was followed by good biological and partial clinicoradiological outcome. The diagnosis of Lyme neuroborreliosis should be entertained as a possible cause of IS in highly endemic zones.

  2. Anterior Ischemic Optic Neuropathy Associated with Udenafil

    PubMed Central

    Kim, In-Gun

    2012-01-01

    We report a case of anterior ischemic optic neuropathy associated with udenafil. A 54-year-old male presented with an acute onset visual field defect of the right eye after udenafil use. Examination revealed a relative afferent pupillary defect and a swollen disc. Automated visual fields revealed an enlarged blind spot and a narrowed visual field. Fluorescein angiography revealed both an inferior choroidal filling delay and an inferior sector filling delay of the optic disc in the arteriovenous phase as well as diffuse leakage of the optic disc in the late phase. Optical coherent tomography revealed increased thickness of the retinal nerve fiber layer, especially in the area of the inferior disc. The patient was counseled to discontinue the use of udenafil and to monitor his blood pressure regularly. The disc swelling was resolved with residual optic atrophy one month after discontinuing the use of udenafil. PMID:22670084

  3. Targeting Neovascularization in Ischemic Retinopathy: Recent Advances

    PubMed Central

    Al-Shabrawey, Mohamed; Elsherbiny, Mohamed; Nussbaum, Julian; Othman, Amira; Megyerdi, Sylvia; Tawfik, Amany

    2014-01-01

    Pathological retinal neovascularization (RNV) is a common micro-vascular complication in several retinal diseases including retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration and central vein occlusion. The current therapeutic modalities of RNV are invasive and although they may slow or halt the progression of the disease they are unlikely to restore normal acuity. Therefore, there is an urgent need to develop treatment modalities, which are less invasive and therefore associated with fewer procedural complications and systemic side effects. This review article summarizes our understanding of the pathophysiology and current treatment of RNV in ischemic retinopathies; lists potential therapeutic targets; and provides a framework for the development of future treatment modalities. PMID:25598837

  4. Brain natriuretic peptide in acute ischemic stroke.

    PubMed

    Maruyama, Kenji; Shiga, Tsuyoshi; Iijima, Mutsumi; Moriya, Saori; Mizuno, Satoko; Toi, Sono; Arai, Kotaro; Ashihara, Kyomi; Abe, Kayoko; Uchiyama, Shinichiro

    2014-01-01

    Elevated serum brain natriuretic peptide (BNP) levels are associated with cardioembolic stroke mainly because of atrial fibrillation (AF). However, the mechanisms of increased serum BNP levels are hitherto unclear. We aimed to identify the factors associated with increased BNP levels in patients with acute ischemic stroke. We measured serum BNP levels in consecutive patients aged 18 years or older. Stroke subtypes were classified using the Trial of ORG 10172 in Acute Stroke Treatment criteria. Categorical variables included age, sex, smoking status, alcohol consumption status, hypertension, diabetes mellitus, dyslipidemia, coronary artery disease (CAD), AF, antiplatelet therapy, and anticoagulant therapy. Continuous variables included hemoglobin, creatinine (Cr), β-thromboglobulin, platelet factor 4, thrombin-antithrombin complex, and d-dimer levels. We further determined the relationship between serum BNP and intima-media thickness, left ventricular ejection fraction, size of infarction, National Institutes of Health Stroke Scale score on admission, and modified Rankin Scale (mRS) score at discharge. Of the 231 patients (mean age, 71 ± 12 years) with acute ischemic stroke (AIS), 36% were women. Serum BNP levels significantly correlated with CAD, AF, Cr, mRS, and cardioembolism (CE) (Dunnett method, P = .004). BNP levels were significantly higher in patients with larger infarcts, higher mRS scores, and higher CHADS2 scores. The levels were higher in patients with larger infarcts, higher mRS scores at discharge, and higher CHADS2 scores among AF patients. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. Molecular mechanisms of ischemic preconditioning in the kidney

    PubMed Central

    Haase, Volker H.

    2015-01-01

    More effective therapeutic strategies for the prevention and treatment of acute kidney injury (AKI) are needed to improve the high morbidity and mortality associated with this frequently encountered clinical condition. Ischemic and/or hypoxic preconditioning attenuates susceptibility to ischemic injury, which results from both oxygen and nutrient deprivation and accounts for most cases of AKI. While multiple signaling pathways have been implicated in renoprotection, this review will focus on oxygen-regulated cellular and molecular responses that enhance the kidney's tolerance to ischemia and promote renal repair. Central mediators of cellular adaptation to hypoxia are hypoxia-inducible factors (HIFs). HIFs play a crucial role in ischemic/hypoxic preconditioning through the reprogramming of cellular energy metabolism, and by coordinating adenosine and nitric oxide signaling with antiapoptotic, oxidative stress, and immune responses. The therapeutic potential of HIF activation for the treatment and prevention of ischemic injuries will be critically examined in this review. PMID:26311114

  6. Normobaric oxygen treatment in acute ischemic stroke: a clinical perspective

    PubMed Central

    Shi, Shu-hai; Qi, Zhi-feng; Luo, Yu-min; Ji, Xun-ming; Liu, Ke Jian

    2016-01-01

    Acute ischemic stroke is a common and serious neurological disease. Oxygen therapy has been shown to increase oxygen supply to ischemic tissues and improve outcomes after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBO), an easily applicable and non-invasive method, shows protective effects on acute ischemic stroke animals and patients in pilot studies. However, many critical scientific questions are still unclear, such as the therapeutic time window of NBO, the long-term effects and the benefits of NBO in large clinic trials. In this article, we review the current literatures on NBO treatment of acute ischemic stroke in preclinical and clinical studies and try to analyze and identify the key gaps or unknowns in our understanding about NBO. Based on these analyses, we provide suggestions for future studies. PMID:27867482

  7. Ischemia reperfusion injury, ischemic conditioning and diabetes mellitus.

    PubMed

    Lejay, Anne; Fang, Fei; John, Rohan; Van, Julie A D; Barr, Meredith; Thaveau, Fabien; Chakfe, Nabil; Geny, Bernard; Scholey, James W

    2016-02-01

    Ischemia/reperfusion, which is characterized by deficient oxygen supply and subsequent restoration of blood flow, can cause irreversible damages to tissue. Mechanisms contributing to the pathogenesis of ischemia reperfusion injury are complex, multifactorial and highly integrated. Extensive research has focused on increasing organ tolerance to ischemia reperfusion injury, especially through the use of ischemic conditioning strategies. Of morbidities that potentially compromise the protective mechanisms of the heart, diabetes mellitus appears primarily important to study. Diabetes mellitus increases myocardial susceptibility to ischemia reperfusion injury and also modifies myocardial responses to ischemic conditioning strategies by disruption of intracellular signaling responsible for enhancement of resistance to cell death. The purpose of this review is twofold: first, to summarize mechanisms underlying ischemia reperfusion injury and the signal transduction pathways underlying ischemic conditioning cardioprotection; and second, to focus on diabetes mellitus and mechanisms that may be responsible for the lack of effect of ischemic conditioning strategies in diabetes.

  8. Role of inflammation and its mediators in acute ischemic stroke

    PubMed Central

    Jin, Rong; Liu, Lin; Zhang, Shihao; Nanda, Anil; Li, Guohong

    2013-01-01

    Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Increasing evidence suggests that inflammatory response is a double-edged sword, as it not only exacerbates secondary brain injury in the acute stage of stroke but also beneficially contributes to brain recovery after stroke. In this article, we provide an overview on the role of inflammation and its mediators in acute ischemic stroke. We discuss various pro-inflammatory and anti-inflammatory responses in different phases after ischemic stroke and the possible reasons for their failures in clinical trials. Undoubtedly, there is still much to be done in order to translate promising pre-clinical findings into clinical practice. A better understanding of the dynamic balance between pro- and anti-inflammatory responses and identifying the discrepancies between pre-clinical studies and clinical trials may serve as a basis for designing effective therapies. PMID:24006091

  9. Sexual dimorphism in ischemic stroke: lessons from the laboratory

    PubMed Central

    Manwani, Bharti; McCullough, Louise D

    2011-01-01

    Ischemic stroke is emerging as a major health problem for elderly women. Women have lower stroke incidence than men until an advanced age, when the epidemiology of ischemic stroke shifts and incidence rises dramatically in women. Experimental models of rodent stroke have replicated this clinical epidemiology, with exacerbated injury in older compared with young female rodents Many of the detrimental effects of aging on ischemic stroke outcome in females can be replicated by ovariectomy, suggesting that hormones such as estrogen play a neuroprotective role. However, emerging data suggest that the molecular mechanisms leading to ischemic cell death differ in the two sexes, and these effects may be independent of circulating hormone levels. This article highlights recent clinical and experimental literature on sex differences in stroke outcomes and mechanisms. PMID:21612353

  10. [Preditive clinical factors for epileptic seizures after ischemic stroke].

    PubMed

    Fukujima, M M; Cardeal, J O; Lima, J G

    1996-06-01

    Preditive clinical factors for epileptic seizures after ischemic stroke. Clinical features of 35 patients with ischemic stroke who developed epilepsy (Group 1) were compared with those of 35 patients with ischemic stroke without epilepsy (Group 2). The age of the patients did not differ between the groups. There were more men than women and more white than other races in both groups. Diabetes melitus, hypertension, transient ischemic attack, previous stroke, migraine, Chagas disease, cerebral embolism of cardiac origin and use of oral contraceptive did not differ between the groups. Smokers and alcohol users were more frequent in Group 1 (p < 0.05). Most patients of Group 1 presented with hemiparesis; none presented cerebellar or brainstem involvement. Perhaps strokes in smokers have some different aspects, that let them more epileptogenic than in non smokers.

  11. Therapeutically targeting neuroinflammation and microglia after acute ischemic stroke.

    PubMed

    Lee, Youngjeon; Lee, Sang-Rae; Choi, Sung S; Yeo, Hyeon-Gu; Chang, Kyu-Tae; Lee, Hong J

    2014-01-01

    Inflammation has a pivotal role in the pathogenesis of ischemic stroke, and recent studies posit that inflammation acts as a double-edged sword, not only detrimentally augmenting secondary injury, but also potentially promoting recovery. An initial event of inflammation in ischemic stroke is the activation of microglia, leading to production of both pro- and anti-inflammatory mediators acting through multiple receptor signaling pathways. In this review, we discuss the role of microglial mediators in acute ischemic stroke and elaborate on preclinical and clinical studies focused on microglia in stroke models. Understanding how microglia can lead to both pro- and anti-inflammatory responses may be essential to implement therapeutic strategies using immunomodulatory interventions in ischemic stroke.

  12. The Migraine-Ischemic Stroke Relation in Young Adults

    PubMed Central

    Pezzini, Alessandro; Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Dalla Volta, Giorgio; Padovani, Alessandro

    2011-01-01

    In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1) the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2) migraine is associated with an increased prevalence of cardiovascular risk factors; (3) the link is caused by migraine-specific drugs; (4) migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions. PMID:21197470

  13. Developing practice recommendations for endovascular revascularization for acute ischemic stroke

    PubMed Central

    Lazzaro, Marc A.; Alexandrov, Andrei V.; Darkhabani, Ziad; Edgell, Randall C.; English, Joey; Frei, Donald; Jamieson, Dara G.; Janardhan, Vallabh; Janjua, Nazli; Janjua, Rashid M.; Katzan, Irene; Khatri, Pooja; Kirmani, Jawad F.; Liebeskind, David S.; Linfante, Italo; Nguyen, Thanh N.; Saver, Jeffrey L.; Shutter, Lori; Xavier, Andrew; Yavagal, Dileep; Zaidat, Osama O.

    2012-01-01

    Guidelines have been established for the management of acute ischemic stroke; however, specific recommendations for endovascular revascularization therapy are lacking. Burgeoning investigation of endovascular revascularization therapies for acute ischemic stroke, rapid device development, and a diverse training background of the providers performing the procedures underscore the need for practice recommendations. This review provides a concise summary of the Society of Vascular and Interventional Neurology endovascular acute ischemic stroke roundtable meeting. This document was developed to review current clinical efficacy of pharmacologic and mechanical revascularization therapy, selection criteria, periprocedure management, and endovascular time metrics and to highlight current practice patterns. It therefore provides an outline for the future development of multisociety guidelines and recommendations to improve patient selection, procedural management, and organizational strategies for revascularization therapies in acute ischemic stroke. PMID:23008406

  14. In vivo characterization of ischemic small intestine using bioimpedance measurements.

    PubMed

    Strand-Amundsen, R J; Tronstad, C; Kalvøy, H; Gundersen, Y; Krohn, C D; Aasen, A O; Holhjem, L; Reims, H M; Martinsen, Ø G; Høgetveit, J O; Ruud, T E; Tønnessen, T I

    2016-02-01

    The standard clinical method for the assessment of viability in ischemic small intestine is still visual inspection and palpation. This method is non-specific and unreliable, and requires a high level of clinical experience. Consequently, viable tissue might be removed, or irreversibly damaged tissue might be left in the body, which may both slow down patient recovery. Impedance spectroscopy has been used to measure changes in electrical parameters during ischemia in various tissues. The physical changes in the tissue at the cellular and structural levels after the onset of ischemia lead to time-variant changes in the electrical properties. We aimed to investigate the use of bioimpedance measurement to assess if the tissue is ischemic, and to assess the ischemic time duration. Measurements were performed on pigs (n = 7) using a novel two-electrode setup, with a Solartron 1260/1294 impedance gain-phase analyser. After induction of anaesthesia, an ischemic model with warm, full mesenteric arterial and venous occlusion on 30 cm of the jejunum was implemented. Electrodes were placed on the serosal surface of the ischemic jejunum, applying a constant voltage, and measuring the resulting electrical admittance. As a control, measurements were done on a fully perfused part of the jejunum in the same porcine model. The changes in tan δ (dielectric parameter), measured within a 6 h period of warm, full mesenteric occlusion ischemia in seven pigs, correlates with the onset and duration of ischemia. Tan δ measured in the ischemic part of the jejunum differed significantly from the control tissue, allowing us to determine if the tissue was ischemic or not (P < 0.0001, F = (1,75.13) 188.19). We also found that we could use tan δ to predict ischemic duration. This opens up the possibility of real-time monitoring and assessment of the presence and duration of small intestinal ischemia.

  15. Systemic chemokine levels, coronary heart disease, and ischemic stroke events

    PubMed Central

    Canouï-Poitrine, F.; Luc, G.; Mallat, Z.; Machez, E.; Bingham, A.; Ferrieres, J.; Ruidavets, J.-B.; Montaye, M.; Yarnell, J.; Haas, B.; Arveiler, D.; Morange, P.; Kee, F.; Evans, A.; Amouyel, P.; Ducimetiere, P.

    2011-01-01

    Objectives: To quantify the association between systemic levels of the chemokine regulated on activation normal T-cell expressed and secreted (RANTES/CCL5), interferon-γ-inducible protein-10 (IP-10/CXCL10), monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1 (CCL11) with future coronary heart disease (CHD) and ischemic stroke events and to assess their usefulness for CHD and ischemic stroke risk prediction in the PRIME Study. Methods: After 10 years of follow-up of 9,771 men, 2 nested case-control studies were built including 621 first CHD events and 1,242 matched controls and 95 first ischemic stroke events and 190 matched controls. Standardized hazard ratios (HRs) for each log-transformed chemokine were estimated by conditional logistic regression. Results: None of the 4 chemokines were independent predictors of CHD, either with respect to stable angina or to acute coronary syndrome. Conversely, RANTES (HR = 1.70; 95% confidence interval [CI] 1.05–2.74), IP-10 (HR = 1.53; 95% CI 1.06–2.20), and eotaxin-1 (HR = 1.59; 95% CI 1.02–2.46), but not MCP-1 (HR = 0.99; 95% CI 0.68–1.46), were associated with ischemic stroke independently of traditional cardiovascular risk factors, hs-CRP, and fibrinogen. When the first 3 chemokines were included in the same multivariate model, RANTES and IP-10 remained predictive of ischemic stroke. Their addition to a traditional risk factor model predicting ischemic stroke substantially improved the C-statistic from 0.6756 to 0.7425 (p = 0.004). Conclusions: In asymptomatic men, higher systemic levels of RANTES and IP-10 are independent predictors of ischemic stroke but not of CHD events. RANTES and IP-10 may improve the accuracy of ischemic stroke risk prediction over traditional risk factors. PMID:21849651

  16. Amplification of acute focal ischemic deficit by narcotics.

    PubMed

    Dubow, Jordan; Bernstein, Richard A

    2008-01-01

    This article describes two patients with major ischemic stroke symptoms who had extremely small areas of acute brain infarction, suggestive of acute intrahemispheric diaschisis. Both patients were using narcotic analgesics during their stroke, and in both cases the clinical deficits improved dramatically with naloxone. We postulate that the narcotics amplified the ischemic stroke symptoms and that this effect was antagonized by naloxone. This suggests that the opiate system may be involved in the process of intrahemispheric diaschisis.

  17. Cytomegalovirus: associated ischemic colitis in an immunocompetent patient.

    PubMed

    Puerta, Ana; Priego, Pablo; Galindo, Julio

    2017-09-01

    Cytomegalovirus (CMV) colitis is a common entity in immunocompromised patients, being rare among immunocompetent individuals. In addition, its association with ischemic colitis is unusual in both groups of population. Rectal bleeding might occur in both entities and, occasionally, urgent surgical treatment may be required, associating high morbility rates. We report one case of cytomegalovirus colitis associated with severe ischemic colitis in a non- immunocompromised patient with favourable response to conservative management with antiviral therapy.

  18. Plasma Magnesium and the Risk of Ischemic Stroke among Women

    PubMed Central

    Akarolo-Anthony, Sally N.; Jiménez, Monik C.; Chiuve, Stephanie E.; Spiegelman, Donna; Willett, Walter C.; Rexrode, Kathryn M.

    2014-01-01

    Background and Purpose Lower plasma magnesium levels may be associated with higher blood pressure and endothelial dysfunction, but sparse prospective data are available for stroke. Methods Among 32,826 participants in the Nurses’ Health Study who provided blood samples in 1989–1990, incident ischemic strokes were identified and confirmed by medical records through 2006. We conducted a nested case-control analysis of 459 cases, matched 1:1 to controls on age, race/ethnicity, smoking status, date of blood draw, fasting status, menopausal status and hormone use. We used conditional logistic regression models to estimate the multivariable adjusted association of plasma magnesium and the risk of ischemic stroke and ischemic stroke subtypes. Results Median magnesium levels did not differ between ischemic stroke cases and controls (median=0.86 mmol/l for both; p-value=0.14). Conditional on matching factors, women in the lowest magnesium quintile had a relative risk (RR) of 1.34 (95% confidence interval [CI]: 0.86–2.10, p trend=0.13) for total ischemic stroke, compared to women in the highest quintile. Additional adjustment for risk factors and confounders did not substantially alter the risk estimates for total ischemic stroke. Women with magnesium levels <0.82 mmol/l, had significantly greater risk of total ischemic stroke (multivariable RR=1.57; 95% CI: 1.09–2.27, p=0.01), and thrombotic stroke (multivariable RR=1.66; 95% CI: 1.03–2.65, p=0.03) compared to women with magnesium levels ≥0.82 mmol/l. No significant effect modification was observed by age, body mass index, hypertension or diabetes. Conclusions Lower plasma magnesium levels may contribute to higher risk of ischemic stroke among women. PMID:25116874

  19. Dietary intervention in the clinical prevention of ischemic heart disease.

    PubMed

    Jamison, J R

    1990-06-01

    While some scientific doubt lingers with regard to the validity of minimizing mortality rates attributable to ischemic heart disease via nutritional strategies targeted at coronary risk factors, popular consensus is committed to such intervention. Chiropractic respondents largely support the notion that nutritional intervention can indeed facilitate prevention of ischemic heart disease. The precise strategies whereby such disease prevention may be achieved have proven problematic; even respondents who conceptually supported particular intervention strategies demonstrated some hesitation in clinically implementing their beliefs.

  20. Hospital costs of ischemic stroke and TIA in the Netherlands.

    PubMed

    Buisman, Leander R; Tan, Siok Swan; Nederkoorn, Paul J; Koudstaal, Peter J; Redekop, William K

    2015-06-02

    There have been no ischemic stroke costing studies since major improvements were implemented in stroke care. We therefore determined hospital resource use and costs of ischemic stroke and TIA in the Netherlands for 2012. We conducted a retrospective cost analysis using individual patient data from a national diagnosis-related group registry. We analyzed 4 subgroups: inpatient ischemic stroke, inpatient TIA, outpatient ischemic stroke, and outpatient TIA. Costs of carotid endarterectomy and costs of an extra follow-up visit were also estimated. Unit costs were based on reference prices from the Dutch Healthcare Insurance Board and tariffs provided by the Dutch Healthcare Authority. Linear regression analysis was used to examine the association between hospital costs and various patient and hospital characteristics. A total of 35,903 ischemic stroke and 21,653 TIA patients were included. Inpatient costs were €5,328 ($6,845) for ischemic stroke and €2,470 ($3,173) for TIA. Outpatient costs were €495 ($636) for ischemic stroke and €587 ($754) for TIA. Costs of carotid endarterectomy were €6,836 ($8,783). Costs of inpatient days were the largest contributor to hospital costs. Age, hospital type, and region were strongly associated with hospital costs. Hospital costs are higher for inpatients and ischemic strokes compared with outpatients and TIAs, with length of stay (LOS) the most important contributor. LOS and hospital costs have substantially declined over the last 10 years, possibly due to improved hospital stroke care and efficient integrated stroke services. © 2015 American Academy of Neurology.

  1. Apparent diffusion coefficient threshold for delineation of ischemic core

    PubMed Central

    Purushotham, Archana; Campbell, Bruce C. V.; Straka, Matus; Mlynash, Michael; Olivot, Jean-Marc; Bammer, Roland; Kemp, Stephanie M.; Albers, Gregory W.; Lansberg, Maarten G.

    2013-01-01

    Background MRI-based selection of patients for acute stroke interventions requires rapid accurate estimation of the infarct core on diffusion-weighted MRI (DWI). Typically used manual methods to delineate DWI lesions are subjective and time-consuming. These limitations would be overcome by a fully automated method that can rapidly and objectively delineate the ischemic core. An automated method would require pre-defined criteria to identify the ischemic core. Aim To determine Apparent Diffusion Coefficient (ADC) based criteria that can be implemented in a fully automated software solution for identification of the ischemic core. Methods Imaging data from patients enrolled in the DEFUSE study who had early revascularization following tPA treatment, was included. The patients’ baseline DWI and 30-day FLAIR lesions were manually delineated after co-registration. Parts of the DWI lesion that corresponded with 30-day infarct were considered ischemic core, whereas parts that corresponded with normal brain parenchyma at 30 days were considered non-core. The optimal ADC threshold to discriminate core from non-core voxels was determined by voxel-based ROC analysis using the Youden index. Results 51045 DWI positive voxels from 14 patients who met eligibility criteria were analyzed. The mean DWI lesion volume was 24(±23) mL. Of this, 18(±22) mL was ischemic core and 3(±5) mL was non-core. The remainder corresponded to pre-existing gliosis, CSF, or was lost to post-infarct atrophy. The ADC of core was lower than that of non-core voxels (p<0.0001). The optimal threshold for identification of ischemic core was an ADC ≤620 ×10−6 mm2/s (sensitivity 69% and specificity 78%). Conclusions Our data suggests the ischemic core can be identified with an absolute ADC threshold. This threshold can be implemented in image analysis software for fully automated segmentation of the ischemic core. PMID:23802548

  2. Life style modification for patients with ischemic heart disease.

    PubMed

    Mahalingam, V

    2013-01-01

    With a view to assess the effectiveness of lifestyle modification in patients with ischemic heart disease, a quasi-experimental study with quantitative approach was undertaken on 60 patients of ischemic heart disease. Purposive sampling technique was used in selecting the patients. The results showed that educating the patients about cessation of smoking, taking proper diet, anxiety reduction and counselling helped in preventing the progression of ischaemic heart disease.

  3. Serum Uric Acid Levels and Outcomes After Acute Ischemic Stroke.

    PubMed

    Wang, Zhongchao; Lin, Yanlin; Liu, Yuxiu; Chen, Ying; Wang, Bin; Li, Changgui; Yan, Shengli; Wang, Yangang; Zhao, Wenjuan

    2016-04-01

    Previous studies assessing the association between serum uric acid levels and neurological outcome after acute ischemic stroke reported conflicting results. A systematic review and meta-analysis were conducted to assess the impact of serum uric acid levels on outcome after acute ischemic stroke. Pubmed, Embase, Web of Science, and Google scholar were searched through September 26, 2014 to identify eligible published or unpublished studies on the association between serum uric acid levels and outcome after acute ischemic stroke. Hazard ratio (HR) for poor outcome or mean differences of serum uric acid levels with 95% confidence intervals (95% CIs) were pooled using meta-analysis. The primary outcome was occurrence of poor outcomes, while the secondary outcome was the mean differences of serum uric acid levels in patients with good or poor outcomes. Ten eligible studies with a total of 8131 acute ischemic stroke patients were included into the meta-analysis. Compared with low serum uric acid level, high serum uric acid level was associated better outcome after acute ischemic stroke (HR = 0.77, 95% CI 0.68-0.88, P = 0.0001). Sensitivity analysis further identified the prognostic role of serum uric acid levels on outcome after acute ischemic stroke. Patients with good outcomes had a higher serum uric acid level compared with those with poor outcome (mean difference = 30.61 μmol/L, 95% CI 20.13-41.08, P < 0.00001). There was no obvious risk of publication bias in the meta-analysis. This meta-analysis supports that serum uric acid level has a protective effect on neurological outcome after acute ischemic stroke. High uric acid level at the onset is a biomarker of better prognosis in patients with acute ischemic stroke.

  4. Vertebral artery stump syndrome in acute ischemic stroke.

    PubMed

    Kawano, Hiroyuki; Inatomi, Yuichiro; Hirano, Teruyuki; Yonehara, Toshiro

    2013-01-15

    Although the carotid artery stump as an embolic source for ischemic stroke has been well described, there have been few systematic reports of a similar syndrome in the posterior circulation (PC) after vertebral artery (VA) origin occlusion. The aim of this study was to identify the incidence and characteristics of acute ischemic stroke with VA stump syndrome. Of 3463 consecutive patients who were admitted within 7 days after onset, 865 patients with acute ischemic stroke in the PC were enrolled. The diagnostic criteria of VA stump syndrome included: (1) acute ischemic stroke in the posterior circulation; (2) the VA origin occlusion identified on MRA, duplex ultrasound, CT angiography, and/or conventional angiography; (3) presence of distal antegrade flow in the ipsilateral VA; and (4) absence of other causes of ischemic stroke. Of the 865 patients with PC stroke, 12 (1.4%) were diagnosed as having VA stump syndrome. The ischemic lesions included the cerebellum in all patients. Nine patients had multiple ischemic lesions in the brain stem, thalamus, or posterior lobe other than cerebellum. On duplex ultrasound, a to-and-fro flow pattern was observed in the culprit VA in 10 patients. Three patients had recurrences of ischemic stroke in the PC during the acute phase. VA stump syndrome was not a rare mechanism of PC stroke, and there was a high rate of stroke recurrence during the acute phase. Vascular assessment by a multimodality approach can be used to promptly detect VA stump syndrome. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Relationship Between Ischemic Heart Disease and Sexual Satisfaction

    PubMed Central

    Afra, Leila Ghanbari; Taghadosi, Mohsen; Gilasi, Hamid Reza

    2016-01-01

    Aim: Ischemic heart disease is a life-threatening condition. Considerable doubts exist over the effects of this disease on patients’ sexual activity and satisfaction. The aim of this study was to evaluate the relationship between ischemic heart disease and sexual satisfaction. Methods: In a retrospective cohort study, the convenience sample of 150 patients exposure with ischemic heart disease and 150 people without exposure it was drawn from Shahid Beheshti hospital, Kashan, Iran. Sampling was performed from March to September 2014. We employed the Larson’s Sexual Satisfaction Questionnaire for gathering the data. Data were analyzed using descriptive statistics and Chi-square, t-test and linear regression analysis. Results: The means of sexual satisfaction in patients exposure with ischemic heart disease and among the subjects without exposure it were 101.47±13.42 and 100.91±16.52, respectively. There was no significant difference between the two groups regarding sexual satisfaction. However, sexual satisfaction was significantly correlated with gender and the use of cardiac medications (P value < 0.05). Conclusion: The level of sexual satisfaction in patients with exposure ischemic heart disease is similar to the people without exposure it. Moreover, the men and the patients who do not receive cardiac medications have higher levels of sexual satisfaction. Nurses who are providing care to patients with ischemic heart disease need to pay closer attention to patient education about sexual issues. PMID:26234982

  6. The application of remote ischemic conditioning in cardiac surgery

    PubMed Central

    Bosnjak, Zeljko J.; Ge, Zhi-Dong

    2017-01-01

    Perioperative myocardial ischemia and infarction are the leading causes of morbidity and mortality following anesthesia and surgery. The discovery of endogenous cardioprotective mechanisms has led to testing of new methods to protect the human heart. These approaches have included ischemic pre-conditioning, per-conditioning, post-conditioning, and remote conditioning of the myocardium. Pre-conditioning and per-conditioning include brief and repetitive periods of sub-lethal ischemia before and during prolonged ischemia, respectively; and post-conditioning is applied at the onset of reperfusion. Remote ischemic conditioning involves transient, repetitive, non-lethal ischemia and reperfusion in one organ or tissue (remote from the heart) that renders myocardium more resistant to lethal ischemia/reperfusion injury. In healthy, young hearts, many conditioning maneuvers can significantly increase the resistance of the heart against ischemia/reperfusion injury. The large multicenter clinical trials with ischemic remote conditioning have not been proven successful in cardiac surgery thus far. The lack of clinical success is due to underlying risk factors that interfere with remote ischemic conditioning and the use of cardioprotective agents that have activated the endogenous cardioprotective mechanisms prior to remote ischemic conditioning. Future preclinical research using remote ischemic conditioning will need to be conducted using comorbid models. PMID:28690837

  7. Polygenic risk of ischemic stroke is associated with cognitive ability.

    PubMed

    Harris, Sarah E; Malik, Rainer; Marioni, Riccardo; Campbell, Archie; Seshadri, Sudha; Worrall, Bradford B; Sudlow, Cathie L M; Hayward, Caroline; Bastin, Mark E; Starr, John M; Porteous, David J; Wardlaw, Joanna M; Deary, Ian J

    2016-02-16

    We investigated the correlation between polygenic risk of ischemic stroke (and its subtypes) and cognitive ability in 3 relatively healthy Scottish cohorts: the Lothian Birth Cohort 1936 (LBC1936), the Lothian Birth Cohort 1921 (LBC1921), and Generation Scotland: Scottish Family Health Study (GS). Polygenic risk scores for ischemic stroke were created in LBC1936 (n = 1005), LBC1921 (n = 517), and GS (n = 6,815) using genome-wide association study summary data from the METASTROKE collaboration. We investigated whether the polygenic risk scores correlate with cognitive ability in the 3 cohorts. In the largest cohort, GS, polygenic risk of all ischemic stroke, small vessel disease stroke, and large vessel disease stroke, but not cardioembolic stroke, were correlated with both fluid and crystallized cognitive abilities. The highest correlation was between a polygenic risk score for all ischemic stroke and general cognitive ability (r = -0.070, p = 1.95 × 10(-8)). Few correlations were identified in LBC1936 and LBC1921, but a meta-analysis of all 3 cohorts supported the correlation between polygenic risk of ischemic stroke and cognitive ability. The findings from this study indicate that even in the absence of stroke, being at high polygenic risk of ischemic stroke is associated with lower cognitive ability. © 2015 American Academy of Neurology.

  8. Polygenic risk of ischemic stroke is associated with cognitive ability

    PubMed Central

    Malik, Rainer; Marioni, Riccardo; Campbell, Archie; Seshadri, Sudha; Worrall, Bradford B.; Sudlow, Cathie L.M.; Hayward, Caroline; Bastin, Mark E.; Starr, John M.; Porteous, David J.; Wardlaw, Joanna M.; Deary, Ian J.

    2016-01-01

    Objectives: We investigated the correlation between polygenic risk of ischemic stroke (and its subtypes) and cognitive ability in 3 relatively healthy Scottish cohorts: the Lothian Birth Cohort 1936 (LBC1936), the Lothian Birth Cohort 1921 (LBC1921), and Generation Scotland: Scottish Family Health Study (GS). Methods: Polygenic risk scores for ischemic stroke were created in LBC1936 (n = 1005), LBC1921 (n = 517), and GS (n = 6,815) using genome-wide association study summary data from the METASTROKE collaboration. We investigated whether the polygenic risk scores correlate with cognitive ability in the 3 cohorts. Results: In the largest cohort, GS, polygenic risk of all ischemic stroke, small vessel disease stroke, and large vessel disease stroke, but not cardioembolic stroke, were correlated with both fluid and crystallized cognitive abilities. The highest correlation was between a polygenic risk score for all ischemic stroke and general cognitive ability (r = −0.070, p = 1.95 × 10−8). Few correlations were identified in LBC1936 and LBC1921, but a meta-analysis of all 3 cohorts supported the correlation between polygenic risk of ischemic stroke and cognitive ability. Conclusions: The findings from this study indicate that even in the absence of stroke, being at high polygenic risk of ischemic stroke is associated with lower cognitive ability. PMID:26695942

  9. Clinical Correlates, Ethnic Differences, and Prognostic Implications of Perivascular Spaces in Transient Ischemic Attack and Ischemic Stroke.

    PubMed

    Lau, Kui-Kai; Li, Linxin; Lovelock, Caroline E; Zamboni, Giovanna; Chan, Tsz-Tai; Chiang, Man-Fung; Lo, Kin-Ting; Küker, Wilhelm; Mak, Henry Ka-Fung; Rothwell, Peter M

    2017-06-01

    Perivascular spaces (PVSs) are considered markers of small vessel disease. However, their long-term prognostic implications in transient ischemic attack/ischemic stroke patients are unknown. Ethnic differences in PVS prevalence are also unknown. Two independent prospective studies were conducted, 1 comprising predominantly whites with transient ischemic attack/ischemic stroke (OXVASC [Oxford Vascular] study) and 1 comprising predominantly Chinese with ischemic stroke (University of Hong Kong). Clinical and imaging correlates, prognostic implications for stroke and death, and ethnic differences in basal ganglia (BG) and centrum semiovale (CS) PVSs were studied with adjustment for age, sex, vascular risk factors, and scanner strength. Whites with transient ischemic attack/ischemic stroke (n=1028) had a higher prevalence of both BG and CS-PVSs compared with Chinese (n=974; >20 BG-PVSs: 22.4% versus 7.1%; >20 CS-PVSs: 45.8% versus 10.4%; P<0.0001). More than 20 BG or CS-PVSs were both associated with increasing age and white matter hyperintensity, although associations with BG-PVSs were stronger (all P<0.0001). During 6924 patient-years of follow-up, BG-PVSs were also independently associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio compared with <11 PVSs, 11-20 PVSs: HR, 1.15; 95% confidence interval, 0.78-1.68; >20 PVSs: HR, 1.82; 1.18-2.80; P=0.011) but not intracerebral hemorrhage (P=0.10) or all-cause mortality (P=0.16). CS-PVSs were not associated with recurrent stroke (P=0.57) or mortality (P=0.072). Prognostic associations were similar in both cohorts. Over and above ethnic differences in frequency of PVSs in transient ischemic attack/ischemic stroke patients, BG and CS-PVSs had similar risk factors, but although >20 BG-PVSs were associated with an increased risk of recurrent ischemic stroke, CS-PVSs were not. © 2017 The Authors.

  10. Attenuating Ischemic Disruption of K(+) Homeostasis in the Cortex of Hypoxic-Ischemic Neonatal Rats: DOR Activation vs. Acupuncture Treatment.

    PubMed

    Chao, Dongman; Wang, Qinyu; Balboni, Gianfranco; Ding, Guanghong; Xia, Ying

    2016-12-01

    Perinatal hypoxic-ischemic (HI) brain injury results in death or profound long-term neurologic disability in both children and adults. However, there is no effective pharmacological therapy due to a poor understanding of HI events, especially the initial triggers for hypoxic-ischemic injury such as disrupted ionic homeostasis and the lack of effective intervention strategy. In the present study, we showed that neonatal brains undergo a developmental increase in the disruption of K(+) homeostasis during simulated ischemia, oxygen-glucose deprivation (OGD) and neonatal HI cortex has a triple phasic response (earlier attenuation, later enhancement, and then recovery) of disrupted K(+) homeostasis to OGD. This response partially involves the activity of the δ-opioid receptor (DOR) since the earlier attenuation of ischemic disruption of K(+) homeostasis could be blocked by DOR antagonism, while the later enhancement was reversed by DOR activation. Similar to DOR activation, acupuncture, a strategy to promote DOR activity, could partially reverse the later enhanced ischemic disruption of K(+) homeostasis in the neonatal cortex. Since maintaining cellular K(+) homeostasis and inhibiting excessive K(+) fluxes in the early phase of hypoxic-ischemic insults may be of therapeutic benefit in the treatment of ischemic brain injury and related neurodegenerative conditions, and since many neurons and other cells can be rescued during the "window of opportunity" after HI insults, our first findings regarding the role of acupuncture and DOR in attenuating ischemic disruption of K(+) homeostasis in the neonatal HI brain suggest a potential intervention therapy in the treatment of neonatal brain injury, especially hypoxic-ischemic encephalopathy.

  11. A Diagnostic Score for Insulin Resistance in Nondiabetic Patients with Ischemic Stroke or Transient Ischemic Attack.

    PubMed

    Xu, Jin; Viscoli, Catherine M; Ford, Gary A; Gorman, Mark; Kernan, Walter N

    2016-07-01

    We sought to develop an instrument to screen for insulin resistance in nondiabetic patients with recent ischemic stroke or transient ischemic attack (TIA). Subjects were 7262 nondiabetic patients aged greater than or equal to 40 years with ischemic strokes or TIA within the past 6 months. Features were analyzed in bivariate analysis for association with insulin resistance, measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Features significantly associated with HOMA-IR (P < .05) were entered into multivariable analysis. The magnitudes of regression coefficients from the multivariable model were used to assign point values for 2 diagnostic scoring instruments: a basic instrument that did not incorporate laboratory test values and an enhanced instrument that did. The performance of the instruments was tested using receiver operating characteristic (ROC) analysis. In the basic model, 5 features were retained in the multivariable regression analysis: male gender, abdominal obesity, body mass index (BMI), elevated waist-to-hip ratio, and systolic blood pressure. In the enhanced model, 4 features were retained in the multivariable regression analysis: BMI, abdominal obesity, fasting glucose greater than or equal to 100 mg/dL, and triglyceride/high-density lipoprotein ratio. In the basic model, the area under the ROC curve (aROC) was .73 in the validation cohort. In the enhanced model, the aROC was .78 in the validation cohort. Our 2 scoring systems performed well in identifying stroke patients with insulin resistance, but they are probably not sufficiently accurate for high-stake clinical decisions. We suggest strategies for improving the accuracy of future instruments. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  12. Automatic quantification of ischemic injury on diffusion-weighted MRI of neonatal hypoxic ischemic encephalopathy.

    PubMed

    Murphy, Keelin; van der Aa, Niek E; Negro, Simona; Groenendaal, Floris; de Vries, Linda S; Viergever, Max A; Boylan, Geraldine B; Benders, Manon J N L; Išgum, Ivana

    2017-01-01

    A fully automatic method for detection and quantification of ischemic lesions in diffusion-weighted MR images of neonatal hypoxic ischemic encephalopathy (HIE) is presented. Ischemic lesions are manually segmented by two independent observers in 1.5 T data from 20 subjects and an automatic algorithm using a random forest classifier is developed and trained on the annotations of observer 1. The algorithm obtains a median sensitivity and specificity of 0.72 and 0.99 respectively. F1-scores are calculated per subject for algorithm performance (median = 0.52) and observer 2 performance (median = 0.56). A paired t-test on the F1-scores shows no statistical difference between the algorithm and observer 2 performances. The method is applied to a larger dataset including 54 additional subjects scanned at both 1.5 T and 3.0 T. The algorithm findings are shown to correspond well with the injury pattern noted by clinicians in both 1.5 T and 3.0 T data and to have a strong relationship with outcome. The results of the automatic method are condensed to a single score for each subject which has significant correlation with an MR score assigned by experienced clinicians (p < 0.0001). This work represents a quantitative method of evaluating diffusion-weighted MR images in neonatal HIE and a first step in the development of an automatic system for more in-depth analysis and prognostication.

  13. Prediction of ischemic stroke in patients with tissue-defined transient ischemic attack.

    PubMed

    Hayashi, Takeshi; Kato, Yuji; Nagoya, Harumitsu; Ohe, Yasuko; Deguchi, Ichiro; Fukuoka, Takuya; Maruyama, Hajime; Horiuchi, Yohsuke; Nagamine, Yuito; Sano, Hiroyasu; Tanahashi, Norio

    2014-07-01

    The risk of future stroke after transient ischemic attack (TIA) has been widely studied, but most findings were obtained for classically defined TIA (time-defined TIA). A new definition of TIA, that is, tissue-defined TIA, which requires the absence of fresh brain infarction on magnetic resonance imaging, could change stroke risk assessments. We, therefore, aimed to evaluate the risk of future stroke in patients with tissue-defined TIA. We retrospectively reviewed 74 patients with tissue-defined TIA, who could be followed for 2 years. Clinical, laboratory, and radiological data were collected and compared between groups that did and did not develop ischemic stroke within the 2-year period. Ischemic stroke occurred in 11 patients (14.9%). Increased age, hemiparesis, and/or dysarthria during the TIA, old cerebral infarction revealed by magnetic resonance imaging, and large-artery stenosis detected by magnetic resonance angiography and/or ultrasonography tended to increase the risk of future stroke, but no individual factor showed statistically significant effect. TIA etiology did not significantly affect the risk. ABCD2 score, an established score for predicting stroke after time-defined TIA, showed only a weak association with future stroke. In contrast, new scores that we created reliably predicted future stroke; these included the APO (age, paresis, and old cerebral infarction) and APOL (age, paresis, old cerebral infarction, and large-artery stenosis) scores. The areas under the receiver operating characteristic curves were .662, .737, and .807 for ABCD2, APO, and APOL, respectively. Compared with the established measures, our newly created scores could predict future stroke for tissue-defined TIA more reliably. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Remote ischemic postconditioning during percutaneous coronary interventions: remote ischemic postconditioning-percutaneous coronary intervention randomized trial.

    PubMed

    Lavi, Shahar; D'Alfonso, Sabrina; Diamantouros, Pantelis; Camuglia, Anthony; Garg, Pallav; Teefy, Patrick; Jablonsky, George; Sridhar, Kumar; Lavi, Ronit

    2014-04-01

    Remote ischemic preconditioning may result in reduction in infarct size during percutaneous coronary intervention (PCI). It is unclear whether remote ischemic postconditioning (RIPost) will reduce the incidence of myocardial injury after PCI, and whether ischemic conditioning of a larger remote organ (thigh versus arm) would provide further myocardial protection. We randomized 360 patients presenting with stable or unstable angina (28% of patients) and negative Troponin T at baseline to 3 groups: 2 groups received RIPost (induced by ischemia to upper or lower limb), and a third was the control group. RIPost was applied during PCI immediately after stent deployment, by three 5-minute cycles of blood pressure cuff inflation to >200 mm Hg in the arm or thigh (20 mm Hg in the control) with 5-minute breaks between each cycle. The primary end-point was the proportion of patients with Troponin T levels >3×ULN postprocedure (at 6 or 18-24 hours), where ULN stands for upper limit of normal. A total of 120 patients were randomized to each group. There were no differences in baseline characteristics between the 3 groups. The primary outcome occurred in 30%, 35%, and 35% of the arm, thigh, and control groups, respectively (P=0.64). There were no differences in creatine kinase or high sensitivity C-reactive protein levels after PCI or in the incidence of acute kidney injury between the groups. RIPost during PCI did not reduce the incidence of periprocedural myocardial injury. Similar effect was obtained when remote ischemia was induced to the upper or lower limb. http://www.clinicaltrials.gov. Unique identifier: NCT00970827.

  15. Prediction of Recurrent Stroke or Transient Ischemic Attack After Noncardiogenic Posterior Circulation Ischemic Stroke.

    PubMed

    Zhang, Changqing; Wang, Yilong; Zhao, Xingquan; Liu, Liping; Wang, ChunXue; Pu, Yuehua; Zou, Xinying; Pan, Yuesong; Wong, Ka Sing; Wang, Yongjun

    2017-07-01

    Posterior circulation ischemic stroke (IS) is generally considered an illness with a poor prognosis. However, there are no effective rating scales to predict recurrent stroke following it. Therefore, our aim was to identify clinical or radiological measures that could assist in predicting recurrent cerebral ischemic episodes. We prospectively enrolled 723 noncardiogenic posterior circulation IS patients with onset of symptoms <7 days. Stroke risk factors, admission symptoms and signs, topographical distribution and responsible cerebral artery of acute infarcts, and any recurrent IS or transient ischemic attack (TIA) within 1 year were assessed. Cox regression was used to identify risk factors associated with recurrent IS or TIA within the year after posterior circulation IS. A total of 40 patients (5.5%) had recurrent IS or TIA within 1 year of posterior circulation IS. Multivariate Cox regression identified chief complaint with dysphagia (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.69-10.2; P=0.002), repeated TIAs within 3 months before the stroke (HR, 15.4; 95% CI, 5.55-42.5; P<0.0001), responsible artery stenosis ≥70% (HR, 7.91; 95% CI, 1.00-62.6; P=0.05), multisector infarcts (HR, 5.38; 95% CI, 1.25-23.3; P=0.02), and not on antithrombotics treatment at discharge (HR, 3.06; 95% CI, 1.09-8.58; P=0.03) as independent predictors of recurrent IS or TIA. Some posterior circulation IS patients are at higher risk for recurrent IS or TIA. Urgent assessment and preventive treatment should be offered to these patients as soon as possible. © 2017 American Heart Association, Inc.

  16. Transient ischemic attack and acute ischemic stroke: associations with retinal microvascular signs.

    PubMed

    Wang, Jie Jin; Baker, Michelle L; Hand, Peter J; Hankey, Graeme J; Lindley, Richard I; Rochtchina, Elena; Wong, Tien Y; Liew, Gerald; Mitchell, Paul

    2011-02-01

    Small vessel disease plays a role in cerebral events. We aimed to investigate the prevalence and patterns of retinal microvascular signs (surrogates for cerebral small vessel disease) among patients with transient ischemic attack (TIA) or acute stroke and population control subjects. Patients with TIA or acute stroke aged ≥49 years admitted to hospitals in Melbourne and Sydney, Australia, were recruited to the Multi-Centre Retina and Stroke Study (n=693, 2005 to 2007). Control subjects were Blue Mountains Eye Study participants aged ≥49 years without TIAs or stroke (n=3384, 1992 to 1994, west of Sydney). TIA, ischemic stroke, or primary intracerebral hemorrhage was classified using standardized neurological assessments, including neuroimaging. Retinal microvascular signs (retinopathy, focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar light reflex) were assessed from retinal photographs masked to clinical information. Patients with TIA or acute stroke were older than control subjects and more likely to have stroke risk factors. After adjustment for study site and known risk factors, all retinal microvascular signs were more common in patients with TIA or acute stroke than in control subjects (OR, 1.9 to 8.7; P<0.001). Patients with TIA and those with ischemic stroke had similar prevalences of nondiabetic retinopathy (26.9% versus 29.5%; OR, 0.8; 95% CI, 0.5 to 1.6), diabetic retinopathy (55.5% versus 50.0%; OR, 1.3; 95% CI, 0.4 to 3.6), focal arteriolar narrowing (15.6% versus 18.4%; OR, 0.8; 95% CI, 0.4 to 1.5), and arteriovenous nicking (23.0% versus 17.8%; OR, 1.4; 95% CI, 0.7 to 2.7). Patients with TIA and acute stroke may share similar risk factors or pathogenic mechanisms.

  17. Low ankle-brachial index predicts cardiovascular risk after acute ischemic stroke or transient ischemic attack.

    PubMed

    Busch, Markus A; Lutz, Katrin; Röhl, Jens-Eric; Neuner, Bruno; Masuhr, Florian

    2009-12-01

    A low ankle-brachial blood pressure index (ABI) is an established risk marker for cardiovascular disease and mortality in the general population, but little is known about its prognostic value in individuals with acute ischemic stroke or transient ischemic attack (TIA). An inception cohort of 204 patients with acute ischemic stroke or TIA was followed up for a mean of 2.3 years. At baseline, patients underwent ABI measurement and were assessed for risk factors, cardiovascular comorbidities, and cervical or intracranial artery stenosis. The association between low ABI (

  18. Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance

    PubMed Central

    Lehotský, Ján; Tothová, Barbara; Kovalská, Maria; Dobrota, Dušan; Beňová, Anna; Kalenská, Dagmar; Kaplán, Peter

    2016-01-01

    Homocysteine (Hcy) is a toxic, sulfur-containing intermediate of methionine metabolism. Hyperhomocysteinemia (hHcy), as a consequence of impaired Hcy metabolism or defects in crucial co-factors that participate in its recycling, is assumed as an independent human stroke risk factor. Neural cells are sensitive to prolonged hHcy treatment, because Hcy cannot be metabolized either by the transsulfuration pathway or by the folate/vitamin B12 independent remethylation pathway. Its detrimental effect after ischemia-induced damage includes accumulation of reactive oxygen species (ROS) and posttranslational modifications of proteins via homocysteinylation and thiolation. Ischemic preconditioning (IPC) is an adaptive response of the CNS to sub-lethal ischemia, which elevates tissues tolerance to subsequent ischemia. The main focus of this review is on the recent data on homocysteine metabolism and mechanisms of its neurotoxicity. In this context, the review documents an increased oxidative stress and functional modification of enzymes involved in redox balance in experimentally induced hyperhomocysteinemia. It also gives an interpretation whether hyperhomocysteinemia alone or in combination with IPC affects the ischemia-induced neurodegenerative changes as well as intracellular signaling. Studies document that hHcy alone significantly increased Fluoro-Jade C- and TUNEL-positive cell neurodegeneration in the rat hippocampus as well as in the cortex. IPC, even if combined with hHcy, could still preserve the neuronal tissue from the lethal ischemic effects. This review also describes the changes in the mitogen-activated protein kinase (MAPK) protein pathways following ischemic injury and IPC. These studies provide evidence for the interplay and tight integration between ERK and p38 MAPK signaling mechanisms in response to the hHcy and also in association of hHcy with ischemia/IPC challenge in the rat brain. Further investigations of the protective factors leading to ischemic

  19. The changing pattern of ischemic heart disease

    PubMed Central

    Anderson, T. W.

    1973-01-01

    Male and female death rates from all the major forms of cardiovascular disease were approximately equal until about 1920. Since that time the male:female ratio in fatal ischemic heart disease (IHD) has risen dramatically, but some closely related diseases such as cerebrovascular disease and uncomplicated angina pectoris have maintained sex ratios close to unity. It is difficult to reconcile this divergent trend in the sex ratio of IHD with a simple stenotic-thrombotic view of myocardial infarction (MI) and it is suggested that the modern epidemic of MI in men may be the result of a disorder of muscle metabolism (“vulnerable myocardium”) superimposed on a relatively stable background of stenotic-thrombotic arterial disease. The proposed mechanism would also help to explain the selective action of some modern “coronary risk factors” (such as cigarette smoking and physical inactivity) which increase the risk of MI but have little or no effect on the risk of developing cerebrovascular disease or uncomplicated angina pectoris. PMID:4714875

  20. Angiographic findings of ischemic stroke in children.

    PubMed

    Shirane, R; Sato, S; Yoshimoto, T

    1992-12-01

    A cooperative study was undertaken in the Tohoku district of Japan to investigate the relatively rare phenomenon of cerebral infarction in children. The purpose of the present paper is to describe the cerebral angiographic findings in 48 children whose ischemic lesions were confirmed by CT scan. The majority of lesions were considered to be idiopathic. The areas of cerebral infarction appearing in the CT scans were located in the territory of the middle cerebral artery including the basal ganglia. Angiographical abnormalities were observed in 40 patients (83%). The majority occurred in the supraclinoid portion of the internal carotid artery and in the cisternal portion of the middle and anterior cerebral arteries. Multiple lesions, such as in the C1, A1, and M1 or the C1, M1, and M2 segments were observed in 22 cases. These lesions generally appeared in continuation; no bilateral intracranial lesions were observed. Repeated angiography was performed in 22 cases, and in 55% of these some recovery of the lesions was seen.

  1. Pediatric ischemic stroke due to dengue vasculitis.

    PubMed

    Nanda, Subrat Kumar; Jayalakshmi, Sita; Mohandas, Surath

    2014-10-01

    Dengue infection is an important arboviral infection in southeast Asia, especially in India. Neurological manifestations of dengue are increasingly recognized. We report an ischemic stroke due to dengue vasculitis in an 8-year-old child. We present a girl with a short febrile illness followed by episodic severe headache, with gradually progressive hemiparesis and visual impairment. Her brain magnetic resonance imaging revealed multiple infarctions in the anterior and posterior circulation. The magnetic resonance angiogram revealed irregular narrowing of bilateral middle cerebral arteries, right anterior cerebral artery, left posterior cerebral, and bilateral vertebral arteries suggestive of vasculitis. Her dengue serology was strongly positive for immunoglobulin M with 68.9 panbio units. The rest of the evaluation for pediatric stroke was unremarkable. She was treated with intravenous followed by oral corticosteroids and recovered totally with resolution of vasculitis on magnetic resonance angiogram over the next 3 months. This child illustrates possible immune-mediated vasculitis caused by dengue infection which is rather a rare presentation in a child who subsequently recovered well. One should consider dengue in childhood strokes in endemic regions. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Creatine kinase isoforms in ischemic heart disease.

    PubMed

    Wu, A H

    1989-01-01

    The MM and MB isoenzymes of creatine kinase exist in serum as a collection of at least three major MM and two major MB isoforms. Each of these are derived from single tissue MM and MB isoforms, which are converted to these other forms by carboxypeptidase N after their release from necrotic skeletal and myocardial tissue. Measurement of the MM isoforms in ischemic heart disease is useful for early diagnosis of acute myocardial infarction and for the noninvasive determination of coronary artery reperfusion for infarction patients receiving thrombolytic therapy. Because MM is also released in acute skeletal-muscle disease, MB isoform measurements may have the highest clinical sensitivity. These determinations are important for providing objective information to cardiologists who need to make critical decisions concerning the management of these patients. I review the procedures for treating patients with myocardial infarction, the potential role of CK isoforms, and the methods currently available for isoform analysis, including high-resolution electrophoresis, isoelectric and chromatofocusing, and liquid chromatography. Rapid and highly sensitive methods are needed for implementation of CK-MM and MB isoforms for prospective emergency determinations for patients with acute myocardial infarction.

  3. Perfusion Angiography in Acute Ischemic Stroke

    PubMed Central

    Liebeskind, David S.

    2016-01-01

    Visualization and quantification of blood flow are essential for the diagnosis and treatment evaluation of cerebrovascular diseases. For rapid imaging of the cerebrovasculature, digital subtraction angiography (DSA) remains the gold standard as it offers high spatial resolution. This paper lays out a methodological framework, named perfusion angiography, for the quantitative analysis and visualization of blood flow parameters from DSA images. The parameters, including cerebral blood flow (CBF) and cerebral blood volume (CBV), mean transit time (MTT), time-to-peak (TTP), and Tmax, are computed using a bolus tracking method based on the deconvolution of the time-density curve on a pixel-by-pixel basis. The method is tested on 66 acute ischemic stroke patients treated with thrombectomy and/or tissue plasminogen activator (tPA) and also evaluated on an estimation task with known ground truth. This novel imaging tool provides unique insights into flow mechanisms that cannot be observed directly in DSA sequences and might be used to evaluate the impact of endovascular interventions more precisely. PMID:27446232

  4. Human Data Supporting Glyburide in Ischemic Stroke

    PubMed Central

    Sheth, Kevin N.; Simard, J. Marc; Elm, Jordan; Kronenberg, Golo; Kunte, Hagen; Kimberly, W. Taylor

    2016-01-01

    The SUR1-TRPM4 channel is a critical determinant of edema and hemorrhagic transformation after focal ischemia. Blockade of this channel by the small molecule glyburide results in improved survival and neurological outcome in multiple preclinical models of ischemic stroke. A robust, compelling body of evidence suggests that an intravenous (IV) formulation of glyburide, RP-1127, can prevent swelling and improve outcome in patients with stroke. Retrospective studies of diabetic stroke patients show improved outcomes in patients who are continued on sulfonylureas after stroke onset. Early phase II study of MRI and plasma biomarkers support the conclusion that RP-1127 may decrease swelling and hemorrhagic transformation. Finally, the ongoing phase II RP-1127 development program has demonstrated continued safety as well as feasibility of enrollment and tolerability of the intervention. Continued efforts to complete the ongoing phase IIb study and definitive efficacy studies are urgently needed to bring a candidate pharmacotherapy to a population of severe stroke patients that currently have no alternative. PMID:26463916

  5. Human Data Supporting Glyburide in Ischemic Stroke.

    PubMed

    Sheth, Kevin N; Simard, J Marc; Elm, Jordan; Kronenberg, Golo; Kunte, Hagen; Kimberly, W Taylor

    2016-01-01

    The SUR1-TRPM4 channel is a critical determinant of edema and hemorrhagic transformation after focal ischemia. Blockade of this channel by the small molecule glyburide results in improved survival and neurological outcome in multiple preclinical models of ischemic stroke. A robust, compelling body of evidence suggests that an intravenous formulation of glyburide, RP-1127, can prevent swelling and improve outcome in patients with stroke. Retrospective studies of diabetic stroke patients show improved outcomes in patients who are continued on sulfonylureas after stroke onset. An early phase II study using magnetic resonance imaging and plasma biomarkers supports the conclusion that RP-1127 may decrease swelling and hemorrhagic transformation. Finally, the ongoing phase II RP-1127 development program has demonstrated continued safety as well as feasibility of enrollment and tolerability of the intervention. Continued efforts to complete the ongoing phase II study and definitive efficacy studies are needed to bring a candidate pharmacotherapy to a population of severe stroke patients that currently have no alternative.

  6. Hydraulic conductivity of ischemic pulmonary venules.

    PubMed

    Qiao, R L; Sadurski, R; Bhattacharya, J

    1993-04-01

    We report the first determination of lung endothelial barrier properties in ischemic, nonreperfused microvessels. We quantified the endothelial barrier in terms of hydraulic conductivity (Lp) in single pulmonary venules (diameter 20-50 microns) of isolated blood perfused lungs (dog, rat), held at constant inflation pressure (5 cmH2O) with a gas mixture containing 21% oxygen. Lp were determined by our split-drop technique in which an oil drop is first microinjected into a venule and then split by microinjection of a protein solution. Lp was interpreted from measurements of the rate of oil drop movement. Baseline Lp recorded in the first 30 min of perfusion averaged 3.4 +/- 0.9 x 10(-7) ml/(cm2.s.cmH2O). Then, in two separate groups of venules in which we established 1.3 +/- 0.1 h and 3.4 +/- 0.8 h of ischemia, we determined Lp which were, respectively, 145 +/- 6.5 and 308 +/- 13% above baseline (P < 0.05). We conclude that ischemia alone, in the absence of reperfusion, significantly deteriorates the lung endothelial barrier.

  7. Management of refractory ischemic priapism: current perspectives.

    PubMed

    Capece, Marco; Gillo, Arianna; Cocci, Andrea; Garaffa, Giulio; Timpano, Massimiliano; Falcone, Marco

    2017-01-01

    The aim of the present manuscript is to review the current literature on priapism, focusing on the state-of-the-art knowledge of both the diagnosis and the treatment of the refractory ischemic priapism (IP). Pubmed and EMBASE search engines were used to search for words "priapism", "refractory priapism", "penile prosthesis", "diagnosis priapism", "priapism treatment", "penile fibrosis", "priapism therapy". All the studies were carefully examined by the authors and then included in the review. First-line treatment involves ejaculation, physical exercise and cold shower followed by corporal blood aspiration and injection of α-adrenoceptor agonists. Subsequently, a distal or proximal shunt may be considered. If none of the treatment is effective or the priapism episode lasts >48 hours penile prosthesis implantation could be the only option to solve the priapism and treat the ongoing erectile dysfunction. The management of IP is to achieve detumescence of persistent penile erection and to preserve erectile function after resolution of the priapic episode. On the other hand, penile fibrosis and following shortening should be prevented. Early penile prosthesis implantation in patients with refractory IP is able to solve both the priapic episode and prevent the otherwise certain penile shortening. Penile prosthesis implantation is the actual gold standard of care in cases of refractory IP.

  8. Remnant cholesterol and ischemic heart disease.

    PubMed

    Varbo, Anette; Nordestgaard, Børge G

    2014-08-01

    To review recent advances in the field of remnant cholesterol as a contributor to the development of ischemic heart disease (IHD). Epidemiologic, mechanistic, and genetic studies all support a role for elevated remnant cholesterol (=cholesterol in triglyceride-rich lipoproteins) as a contributor to the development of atherosclerosis and IHD. Observational studies show association between elevated remnant cholesterol and IHD, and mechanistic studies show remnant cholesterol accumulation in the arterial wall like LDL-cholesterol (LDL-C) accumulation. Furthermore, large genetic studies show evidence of remnant cholesterol as a causal risk factor for IHD independent of HDL-cholesterol levels. Genetic studies also show that elevated remnant cholesterol is associated with low-grade inflammation, whereas elevated LDL-C is not. There are several pharmacologic ways of lowering remnant cholesterol levels; however, it remains to be seen in large randomized clinical intervention trials if lowering of remnant cholesterol, in individuals with elevated levels, will reduce the risk of IHD. Evidence is emerging for elevated remnant cholesterol being a causal risk factor for IHD. Elevated remnant cholesterol levels likely are part of the explanation of the residual risk of IHD observed after LDL-C has been lowered to recommended levels.

  9. [Blood viscosity in ischemic heart disease].

    PubMed

    Malkun Paz, C; Alvarado Molina, M; Hurtado Figueroa, R; Vargas Cuellar, A; Elizalde Moreno, J

    1987-01-01

    Through a capillary viscometer we measured venous and arterial blood viscosity (BV) in 25 patients with the diagnosis of ischemic heart disease (IHD); 10 of them with unstable angor pectoris (UA) and 15 with acute myocardial infarction (MI). The control group consisted of 100 normal individuals in whom the normal values were 2.70 +/- 0.10 centipoises, where as in patients with AU the values were 4.03 +/- 1.40 centipoises and in the group with MI was 3.65 +/- 1.20 centipoises. Statistically, we correlated the BV obtained in both groups with the following parameters: coronary risk factors, cell blood count; serum glucose, cholesterol and triglycerides as well as the number of coronary arteries involved. The levels of venous and arterial BV were elevated in both groups of patients in comparison with the control group. We concluded that arterial and venous BV is elevated in patients with IHD independently of the hematocrit. This suggest the probability of some other factors such as plasmatic viscosity and platelets aggregation could play a role in the BV elevation of this group of patients.

  10. Recurrent thromboembolic events after ischemic stroke in patients with cancer

    PubMed Central

    Singer, Samuel; Merkler, Alexander E.; Cheng, Natalie T.; Stone, Jacqueline B.; Kamel, Hooman; Iadecola, Costantino; Elkind, Mitchell S.V.; DeAngelis, Lisa M.

    2014-01-01

    Objective: To determine the cumulative rate and characteristics of recurrent thromboembolic events after acute ischemic stroke in patients with cancer. Methods: We retrospectively identified consecutive adult patients with active systemic cancer diagnosed with acute ischemic stroke at a tertiary-care cancer center from 2005 through 2009. Two neurologists independently reviewed all electronic records to ascertain the composite outcome of recurrent ischemic stroke, myocardial infarction, systemic embolism, TIA, or venous thromboembolism. Kaplan-Meier statistics were used to determine cumulative outcome rates. In exploratory analyses, Cox proportional hazard analysis was used to evaluate potential independent associations between a priori selected clinical factors and recurrent thromboembolic events. Results: Among 263 study patients, complete follow-up until death was available in 230 (87%). Most patients had an adenocarcinoma as their underlying cancer (60%) and had systemic metastases (69%). Despite a median survival of 84 days (interquartile range 24–419 days), 90 patients (34%; 95% confidence interval 28%–40%) had 117 recurrent thromboembolic events, consisting of 57 cases of venous thromboembolism, 36 recurrent ischemic strokes, 13 myocardial infarctions, 10 cases of systemic embolism, and one TIA. Kaplan-Meier rates of recurrent thromboembolism were 21%, 31%, and 37% at 1, 3, and 6 months, respectively; cumulative rates of recurrent ischemic stroke were 7%, 13%, and 16%. Adenocarcinoma histology (hazard ratio 1.65, 95% confidence interval 1.02–2.68) was independently associated with recurrent thromboembolism. Conclusions: Patients with acute ischemic stroke in the setting of active cancer (especially adenocarcinoma) face a substantial short-term risk of recurrent ischemic stroke and other types of thromboembolism. PMID:24850486

  11. Persistent Ischemic Stroke Disparities despite Declining Incidence in Mexican Americans

    PubMed Central

    Morgenstern, Lewis B.; Smith, Melinda A.; Sanchez, Brisa N.; Brown, Devin L.; Zahuranec, Darin B.; Garcia, Nelda; Kerber, Kevin A.; Skolarus, Lesli E.; Meurer, William J.; Burke, James F.; Adelman, Eric E.; Baek, Jonggyu; Lisabeth, Lynda D.

    2015-01-01

    Objective To determine trends in ischemic stroke incidence among Mexican Americans and non-Hispanic whites. Methods We performed population-based stroke surveillance from January 1, 2000 to December 31, 2010 in Corpus Christi, Texas. Ischemic stroke patients 45 years and older were ascertained from potential sources, and charts were abstracted. Neurologists validated cases based on source documentation blinded to ethnicity and age. Crude and age-, sex-, and ethnicity-adjusted annual incidence was calculated for first ever completed ischemic stroke. Poisson regression models were used to calculate adjusted ischemic stroke rates, rate ratios, and trends. Results There were 2,604 ischemic strokes in Mexican Americans and 2,042 in non-Hispanic whites. The rate ratios (Mexican American:non-Hispanic white) were 1.94 (95% confidence interval [CI] = 1.67–2.25), 1.50 (95% CI = 1.35– 1.67), and 1.00 (95% CI = 0.90–1.11) among those aged 45 to 59, 60 to 74, and 75 years and older, respectively, and 1.34 (95% CI = 1.23–1.46) when adjusted for age. Ischemic stroke incidence declined during the study period by 35.9% (95% CI = 25.9–44.5). The decline was limited to those aged ≥60 years, and happened in both ethnic groups similarly (p > 0.10), implying that the disparities seen in the 45- to 74-year age group persist unabated. Interpretation Ischemic stroke incidence rates have declined dramatically in the past decade in both ethnic groups for those aged ≥60 years. However, the disparity between Mexican American and non-Hispanic white stroke rates persists in those <75 years of age. Although the decline in stroke is encouraging, additional prevention efforts targeting young Mexican Americans are warranted. PMID:23868398

  12. Persistent ischemic stroke disparities despite declining incidence in Mexican Americans.

    PubMed

    Morgenstern, Lewis B; Smith, Melinda A; Sánchez, Brisa N; Brown, Devin L; Zahuranec, Darin B; Garcia, Nelda; Kerber, Kevin A; Skolarus, Lesli E; Meurer, William J; Burke, James F; Adelman, Eric E; Baek, Jonggyu; Lisabeth, Lynda D

    2013-12-01

    To determine trends in ischemic stroke incidence among Mexican Americans and non-Hispanic whites. We performed population-based stroke surveillance from January 1, 2000 to December 31, 2010 in Corpus Christi, Texas. Ischemic stroke patients 45 years and older were ascertained from potential sources, and charts were abstracted. Neurologists validated cases based on source documentation blinded to ethnicity and age. Crude and age-, sex-, and ethnicity-adjusted annual incidence was calculated for first ever completed ischemic stroke. Poisson regression models were used to calculate adjusted ischemic stroke rates, rate ratios, and trends. There were 2,604 ischemic strokes in Mexican Americans and 2,042 in non-Hispanic whites. The rate ratios (Mexican American:non-Hispanic white) were 1.94 (95% confidence interval [CI] = 1.67-2.25), 1.50 (95% CI = 1.35-1.67), and 1.00 (95% CI = 0.90-1.11) among those aged 45 to 59, 60 to 74, and 75 years and older, respectively, and 1.34 (95% CI = 1.23-1.46) when adjusted for age. Ischemic stroke incidence declined during the study period by 35.9% (95% CI = 25.9-44.5). The decline was limited to those aged ≥60 years, and happened in both ethnic groups similarly (p > 0.10), implying that the disparities seen in the 45- to 74-year age group persist unabated. Ischemic stroke incidence rates have declined dramatically in the past decade in both ethnic groups for those aged ≥60 years. However, the disparity between Mexican American and non-Hispanic white stroke rates persists in those <75 years of age. Although the decline in stroke is encouraging, additional prevention efforts targeting young Mexican Americans are warranted. © 2013 American Neurological Association.

  13. Altering 5-hydroxymethylcytosine modification impacts ischemic brain injury.

    PubMed

    Miao, Zhigang; He, Yuquan; Xin, Ning; Sun, Miao; Chen, Li; Lin, Li; Li, Jizhen; Kong, Jiming; Jin, Peng; Xu, Xingshun

    2015-10-15

    Epigenetic modifications such as cytosine methylation and histone modification are linked to the pathology of ischemic brain injury. Recent research has implicated 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC) via oxidation by ten-eleven translocation (Tet) enzymes, in DNA methylation-related plasticity. Here we show that 5hmC abundance was increased after ischemic injury, and Tet2 was responsible for this increase; furthermore, inhibiting Tet2 expression abolished the increase of 5hmC caused by ischemic injury. The decrease in 5hmC modifications from inhibiting Tet2 activity was accompanied by increased infarct volume after ischemic injury. Genome-wide profiling of 5hmC revealed differentially hydroxymethylated regions (DhMRs) associated with ischemic injury, and DhMRs were enriched among the genes involved in cell junction, neuronal morphogenesis and neurodevelopment. In particular, we found that 5hmC modifications at the promoter region of brain-derived neurotrophic factor (BDNF) increased, which was accompanied by increased BDNF mRNA, whereas the inhibition of Tet2 reduced BDNF mRNA and protein expression. Finally, we show that the abundance of 5hmC in blood samples from patients with acute ischemic stroke was also significantly increased. Together, these data suggest that 5hmC modification could serve as both a potential biomarker and a therapeutic target for the treatment of ischemic stroke. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Remote ischemic preconditioning as treatment for non-ischemic gastrointestinal disorders: Beyond ischemia-reperfusion injury

    PubMed Central

    Camara-Lemarroy, Carlos Rodrigo

    2014-01-01

    Common gastrointestinal diseases such as radiation enteritis (RE), acute pancreatitis, inflammatory bowel diseases (IBD) and drug-induced hepatotoxicity share pathophysiological mechanisms at the molecular level, mostly involving the activation of many pathways of the immune response, ultimately leading to tissue injury. Increased oxidative stress, inflammatory cytokine release, inflammatory cell infiltration and activation and the up-regulation of inflammatory transcription factors participate in the pathophysiology of these complex entities. Treatment varies in each specific disease, but at least in the cases of RE and IBD immunosuppressors are effective. However, full therapeutic responses are not always achieved. The pathophysiology of ischemia-reperfusion (IR) injury shares many of these mechanisms. Brief and repetitive periods of ischemia in an organ or limb have been shown to protect against subsequent major IR injury in distant organs, a phenomenon called remote ischemic preconditioning (RIP). This procedure has been shown to protect the gut, pancreas and liver by modulating many of the same inflammatory mechanisms. Since RIP is safe and tolerable, and has shown to be effective in some recent clinical trials, I suggest that RIP could be used as a physiologically relevant adjunct treatment for non-ischemic gastrointestinal inflammatory conditions. PMID:24707140

  15. [Effects of combined ischemic postconditioning, remote ischemic postconditioning and naloxone postconditioning on focal cerebral ischemia-reperfusion injury in rats].

    PubMed

    Liu, Yi; Liao, Xu; Xue, Fu-shan; Xu, Ya-chao; Xiong, Jun; Yuan, Yu-jing; Wang, Qiang; Liu, Jian-hua; Zhao, Jia-xun

    2011-06-07

    To assess the effects of ischemic postconditioning, remote ischemic postconditioning and naloxone postconditioning on focal cerebral ischemia-reperfusion injury in rats. A total of 110 adult SD rats were randomly divided into 5 groups (n = 22 each). The focal cerebral ischemia-reperfusion injury was induced by a 90-minute occlusion of right middle cerebral artery (MCA) and a 24-hour reperfusion sequentially. Group 1 was of ischemia-reperfusion control; Group 2 ischemic postconditioning induced by three 30-second cycles of MCA occlusion followed by a 30-second reperfusion; Group 3 remote ischemic postconditioning performed via a transient occlusion of right femoral artery at 5 min before the initiation of reperfusion; Group 4 naloxone postconditioning with naloxone 10 mg/kg intraperitoneally injected at the initiation of reperfusion; Group 5 combined ischemic, remote ischemic & naloxone postconditioning performed simultaneously in accordance with the methods used in Groups 2, 3 & 4. The neurologic deficit scores (NDS) were obtained at 2 h & 24 h post-reperfusion. At 24 h post-reperfusion, the anesthetized rat was sacrificed by decapitation and the brain rapidly extracted to assess the size of cerebral infarct (n = 10), detect the cerebral expression of microtubule-associated protein-2 (MAP2) (n = 6), measure the plasma volume of cerebral tissues and quantify the diameter and segment length of cerebral microvessel (n = 6). There were no significant differences in the heart rate (HR) and mean arterial pressure (MAP) among the above five groups at all observed time points (P > 0.05). At 24 h post-reperfusion, the percentage of ischemic cerebral infarct size was 43% ± 6%, 31% ± 4%, 32% ± 5%, 28% ± 6% & 21% ± 7% in ipsilateral hemisphere area (i.e., cerebral infarct severity) in Groups 1-5 respectively. Compared with Group 1, the levels of NDS and cerebral infarct severity significantly decreased at ischemic side in Groups 2-5 (P < 0.05). And the cerebral expression

  16. Cancer-associated ischemic stroke is associated with elevated D-dimer and fibrin degradation product levels in acute ischemic stroke with advanced cancer.

    PubMed

    Kono, Tomoyuki; Ohtsuki, Toshiho; Hosomi, Naohisa; Takeda, Ikuko; Aoki, Shiro; Sueda, Yoshimasa; Ishihara, Kayoko; Nakamura, Takeshi; Yamawaki, Takemori; Matsumoto, Masayasu

    2012-07-01

    Although several studies have reported various causes of ischemic stroke in patients with cancer, only a few have evaluated the clinical relevance of ischemic stroke pathogenesis to cancer. The aim of the present study was to elucidate the clinical characteristics of cancer-associated ischemic stroke. We evaluated 154 ischemic stroke patients without cancer and 57 ischemic stroke patients with cancer who had either received continuous treatment for cancer within 5 years before to the onset of ischemic stroke, or who had been diagnosed with cancer within 1 year after the onset of ischemic stroke. Cancer patients were grouped into "cancer-associated ischemic stroke," the "conventional ischemic stroke," or "other." A total of 15 patients (26%) were classified into the cancer-associated ischemic stroke in cancer patients. In univariate analysis of the cancer-associated ischemic stroke and the others, there were significant differences in the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of d-dimer, fibrin degradation product and hemoglobin. With multivariate regression analysis of those factors, the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of D-dimer and fibrin degradation product remained as statistically independent factors, which were associated with cancer-associated ischemic stroke (n = 111, χ(2) =67.21, P < 0.0001). In acute ischemic stroke, the cancer-associated ischemic stroke is associated with elevated D-dimer and fibrin degradation products, even after controlling hypertension, hyperlipidemia and advanced cancer (clinical stage IV). © 2012 Japan Geriatrics Society.

  17. Strictly lobar microbleeds are associated with executive impairment in patients with ischemic stroke or transient ischemic attack.

    PubMed

    Gregoire, Simone M; Scheffler, Grit; Jäger, Hans R; Yousry, Tarek A; Brown, Martin M; Kallis, Constantinos; Cipolotti, Lisa; Werring, David J

    2013-05-01

    Cerebral microbleeds (CMBs) are a marker of small vessel diseases, including hypertensive arteriopathy and cerebral amyloid angiopathy, and may be associated with cognitive impairment. The relationship between CMBs and cognitive function in ischemic cerebrovascular disease remains uncertain. We, therefore, investigated the cognitive impact of CMBs in a cohort of patients with ischemic stroke or transient ischemic attack. All patients underwent detailed and comprehensive neuropsychological testing and standardized MRI, including fluid attenuation inversion recovery, T1, T2, and gradient-recalled echo T2*-weighted sequences. CMBs, white matter changes, lacunes, and territorial cortical infarcts (defined by standardized criteria) were identified, and associations with cognition assessed. Three hundred twenty patients with a diagnosis of ischemic stroke or transient ischemic attack were included. Of these, 72 (22.5%) had at least 1 CMB. Of all the cognitive domains tested, only executive impairment was more prevalent in patients with CMBs than without (38% versus 25%; P=0.039). In univariate analysis, the presence of strictly lobar (but not deep) CMBs was associated with executive impairment (odds ratio, 2.49; 95% confidence interval, 1.16-5.36; P=0.019). In adjusted multivariate analyses, the presence (OR, 2.34; 95% confidence interval, 1.08-5.09; P=0.031) and number (OR, 1.33; 95% confidence interval, 1.04-1.69; P=0.022) of strictly lobar CMBs were significantly associated with executive impairment. CMBs were not associated with impairment in other cognitive domains. Strictly lobar CMBs are independently associated with executive dysfunction in patients with ischemic stroke or transient ischemic attack. Our findings suggest that a microangiopathy related to strictly lobar CMBs (eg, cerebral amyloid angiopathy) contributes to cognitive impairment in this population.

  18. Pre-ischemic treadmill training alleviates brain damage via GLT-1-mediated signal pathway after ischemic stroke in rats.

    PubMed

    Wang, X; Zhang, M; Yang, S-D; Li, W-B; Ren, S-Q; Zhang, J; Zhang, F

    2014-08-22

    Physical exercise could play a neuroprotective role in both human and animals. However, the involved signal pathways underlying the neuroprotective effect are still not well established. This study was to investigate the possible signal pathways involved in the neuroprotection of pre-ischemic treadmill training after ischemic stroke. Seventy-two SD rats were randomly assigned into three groups (n=24/group): sham surgery group, middle cerebral artery occlusion (MCAO) group and MCAO with exercise group. Following three weeks of treadmill training exercise, ischemic stroke was induced by occluding the middle cerebral artery (MCA) in rat for 2 h, followed by reperfusion. Twenty-four hours after MCAO/reperfusion, 12 rats in each group were evaluated for neurological deficit scores and then sacrificed to measure the infarct volume (n=6) and cerebral edema (n=6). Six rats in each group were sacrificed to measure the expression level of glutamate transporter-1 (GLT-1), protein kinase C-α (PKC-α), Akt, and phosphatidylinositol 3 kinase (PI3K) (n=6). Two hundred and eighty minutes (4.67 h) after occlusion, six rats in each group were decapitated to detect the mRNA expression level of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor subunit type 2B (NR2B) (n=6).The results demonstrated that pre-ischemic treadmill training exercise reduced brain infarct volume, cerebral edema and neurological deficits, also decreased the over expression of PKC-α and increased the expression level of GLT-1, Akt and PI3K after ischemic stroke (p<0.05). The over-expression of mGluR5 and NR2B mRNA was also inhibited by pre-ischemic exercise (p<0.05). In summary, exercise preconditioning ameliorated brain damage after ischemic stroke, which might be involved in two signal pathways: PKC-α-GLT-1-Glutamate and PI3K/Akt-GLT-1-Glutamate.

  19. Nontraumatic convexal subarachnoid hemorrhage concomitant with acute ischemic stroke.

    PubMed

    Nakajima, Makoto; Inatomi, Yuichiro; Yonehara, Toshiro; Hirano, Teruyuki; Ando, Yukio

    2014-07-01

    Nontraumatic convexal subarachnoid hemorrhage (cSAH) rarely occurs subsequent to acute ischemic stroke. The incidence, clinical background characteristics, and outcomes in acute ischemic stroke patients with cSAH were investigated. Our stroke center database was reviewed to identify patients with acute ischemic stroke/transient ischemic attack (TIA) who demonstrated acute cSAH within 14 days of admission between 2005 and 2011. Background characteristics, clinical course, and outcomes at discharge and 3 months after onset were investigated in these patients. Of 4953 acute stroke/TIA patients, cSAH was observed in 8 (.14%) patients (7 men, mean age 71 years): 7 were detected incidentally, and the other was found immediately after a convulsion. Two patients died during their hospital stay, 1 died after discharge, and 3 were dependent at 3 months. Major artery occlusion or severe stenosis was observed in 5 patients. Two patients subsequently developed subcortical hemorrhage. On gradient echo imaging, lobar cerebral microbleeds were observed in 2 patients, and chronic superficial siderosis was observed in 2 patients. In this retrospective review of cases with ischemic stroke and cSAH, over half of patients had occlusion of major arteries. Cerebral amyloid angiopathy was suggested by magnetic resonance imaging findings and subsequent events in 3 patients. The overall outcome was unfavorable although the causal relationship with cSAH was unclear. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. Hypothermia therapy for newborns with hypoxic ischemic encephalopathy.

    PubMed

    Silveira, Rita C; Procianoy, Renato S

    2015-01-01

    Therapeutic hypothermia reduces cerebral injury and improves the neurological outcome secondary to hypoxic ischemic encephalopathy in newborns. It has been indicated for asphyxiated full-term or near-term newborn infants with clinical signs of hypoxic-ischemic encephalopathy (HIE). A search was performed for articles on therapeutic hypothermia in newborns with perinatal asphyxia in PubMed; the authors chose those considered most significant. There are two therapeutic hypothermia methods: selective head cooling and total body cooling. The target body temperature is 34.5 °C for selective head cooling and 33.5 °C for total body cooling. Temperatures lower than 32 °C are less neuroprotective, and temperatures below 30 °C are very dangerous, with severe complications. Therapeutic hypothermia must start within the first 6h after birth, as studies have shown that this represents the therapeutic window for the hypoxic-ischemic event. Therapy must be maintained for 72 h, with very strict control of the newborn's body temperature. It has been shown that therapeutic hypothermia is effective in reducing neurologic impairment, especially in full-term or near-term newborns with moderate hypoxic-ischemic encephalopathy. Therapeutic hypothermia is a neuroprotective technique indicated for newborn infants with perinatal asphyxia and hypoxic-ischemic encephalopathy. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  1. Effect of first myocardial ischemic event on renal function.

    PubMed

    Eijkelkamp, Wouter B A; de Graeff, Pieter A; van Veldhuisen, Dirk J; van Dokkum, Richard P E; Gansevoort, Ronald T; de Jong, Paul E; de Zeeuw, Dick; Hillege, Hans L

    2007-07-01

    Effects of cardiovascular dysfunction on renal function have been poorly characterized. Therefore, we investigated the relation between a first ischemic cardiac event and long-term renal function changes in the general population from the PREVEND study. We studied 6,360 subjects with a total follow-up duration of 27.017 subject-years. The estimated mean proportional increase in serum creatinine after a first ischemic cardiac event was 3.1% compared with 0.4% per year of follow-up in subjects without such an event (p = 0.005). This represented a significantly larger decrease in estimated glomerular filtration rate after the event in subjects with an event versus the decrease in subjects without a first ischemic cardiac event (2.2 vs 0.5 ml/min/1.73 m(2)/year of follow-up, p = 0.006). In multivariate analysis with adjustment for renal risk factors, this event showed an independent association with serum creatinine change. In conclusion, a first ischemic cardiac event appears to enhance the natural decrease in renal function. Because even mild renal dysfunction should be considered a major cardiovascular risk factor after myocardial infarction, increased renal function loss after an ischemic cardiac event could add to the risk for subsequent cardiovascular morbidity, thus closing a vicious circle.

  2. Rotating night shift work and the risk of ischemic stroke.

    PubMed

    Brown, Devin L; Feskanich, Diane; Sánchez, Brisa N; Rexrode, Kathryn M; Schernhammer, Eva S; Lisabeth, Lynda D

    2009-06-01

    Rotating night shift work disrupts circadian rhythms and is associated with coronary heart disease. The relation between rotating night shift work and ischemic stroke is unclear. The Nurses' Health Study, an ongoing cohort study of registered female nurses, assessed in 1988 the total number of years the nurses had worked rotating night shifts. The majority (69%) of stroke outcomes from 1988 to 2004 were confirmed by physician chart review. The authors used Cox proportional hazards models to assess the relation between years of rotating night shift work and ischemic stroke, adjusting for multiple vascular risk factors. Of 80,108 subjects available for analysis, 60% reported at least 1 year of rotating night shift work. There were 1,660 ischemic strokes. Rotating night shift work was associated with a 4% increased risk of ischemic stroke for every 5 years (hazard ratio = 1.04, 95% confidence interval: 1.01, 1.07; P(trend) = 0.01). This increase in risk was similar when limited to the 1,152 confirmed ischemic strokes (hazard ratio = 1.03, 95% confidence interval: 0.99, 1.07; P(trend) = 0.10) and may be confined to women with a history of 15 or more years of rotating shift work. Women appear to have a modestly increased risk of stroke after extended periods of rotating night shift work.

  3. Dynamic Changes in DNA Methylation in Ischemic Tolerance

    PubMed Central

    Meller, Robert; Pearson, Andrea; Simon, Roger P.

    2015-01-01

    Epigenetic mediators of gene expression are hypothesized to regulate transcriptomic responses to preconditioning ischemia and ischemic tolerance. Here, we utilized a methyl-DNA enrichment protocol and sequencing (ChIP-seq) to identify patterns of DNA methylation in an established model of ischemic tolerance in neuronal cultures (oxygen and glucose deprivation: OGD). We observed an overall decrease in global DNA methylation at 4 h following preconditioning ischemia (30 min OGD), harmful ischemia (120 min OGD), and in ischemic tolerant neuronal cultures (30 min OGD, 24 h recovery, 120 min OGD). We detected a smaller cohort of hypermethylated regions following ischemic conditions, which were further analyzed revealing differential chromosomal localization of methylation, and a differential concentration of methylation on genomic regions. Together, these data show that the temporal profiles of DNA methylation with respect to chromatin hyper- and hypo-methylation following various ischemic conditions are highly dynamic, and may reveal novel targets for neuroprotection. PMID:26029158

  4. Migraine prophylaxis, ischemic depolarizations and stroke outcomes in mice

    PubMed Central

    Eikermann-Haerter, Katharina; Lee, Jeong Hyun; Yalcin, Nilufer; Yu, Esther Sori; Daneshmand, Ali; Wei, Ying; Zheng, Yi; Can, Anil; Sengul, Buse; Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.; Ayata, Cenk

    2014-01-01

    Background and Purpose Migraine with aura is an established stroke risk factor, and excitatory mechanisms such as spreading depression are implicated in the pathogenesis of both migraine and stroke. Spontaneous spreading depression waves originate within the peri-infarct tissue and exacerbate the metabolic mismatch during focal cerebral ischemia. Genetically enhanced spreading depression susceptibility facilitates anoxic depolarizations and peri-infarct spreading depressions and accelerates infarct growth, suggesting that susceptibility to spreading depression is a critical determinant of vulnerability to ischemic injury. Because chronic treatment with migraine prophylactic drugs suppresses spreading depression susceptibility, we tested whether migraine prophylaxis can also suppress ischemic depolarizations and improve stroke outcome. Methods We measured the cortical susceptibility to spreading depression and ischemic depolarizations, and determined tissue and neurological outcome after middle cerebral artery occlusion in wild type and familial hemiplegic migraine type 1 knock-in mice treated with vehicle, topiramate or lamotrigine daily for 7 weeks or as a single dose shortly before testing. Results Chronic treatment with topiramate or lamotrigine reduces the susceptibility to KCl- or electrical stimulation-induced spreading depressions as well as ischemic depolarizations in both wild-type and familial hemiplegic migraine type 1 mutant mice. Consequently, both tissue and neurological outcomes are improved. Notably, treatment with a single dose of either drug is ineffective. Conclusions These data underscore the importance of hyperexcitability as a mechanism for increased stroke risk in migraineurs, and suggest that migraine prophylaxis may not only prevent migraine attacks but also protect migraineurs against ischemic injury. PMID:25424478

  5. Stroke bricks - spatial brain regions to assess ischemic stroke localization.

    PubMed

    Ciszek, Bogdan; Jóźwiak, Rafał; Sobieszczuk, Ewa; Przelaskowski, Artur; Skadorwa, Tymon

    2017-03-29

    Computer-aided analysis of non-contrast CT (NCCT) images for rapid diagnosis of ischemic stroke is based on the augmented visualization of evolving ischemic lesions. Computerized support of NCCT often leads to overinterpretation of ischemic areas, thus it is of great interest to provide neurologically verified regions in order to improve accuracy of subsequent radiological assessment. We propose Stroke Bricks (StBr) as an arbitrary spatial division of brain tissue into the regions associated with specific clinical symptoms of ischemic stroke. Neurological stroke deficit is formally translated into respective areas of possible ischemic lesions. StBr were designed according to formalized mapping of neurological symptoms and were attributed to the uniquely defined areas of impaired blood supply. StBr concept may be useful for an integrated radiological CT-based assessment of suspected stroke cases or can be included into computer-aided tools to optimize the evaluation of stroke site and its extent. These data in turn are appropriable for further diagnosis, predicting the therapeutic outcome as well as for patients' qualification for an appropriate form of reperfusion therapy. The usefulness of Stroke Bricks was illustrated in the case studies.

  6. Novel pathogenetic mechanisms and structural adaptations in ischemic mitral regurgitation.

    PubMed

    Silbiger, Jeffrey J

    2013-10-01

    Ischemic mitral regurgitation (MR) is a common complication of myocardial infarction thought to result from leaflet tethering caused by displacement of the papillary muscles that occurs as the left ventricle remodels. The author explores the possibility that left atrial remodeling may also play a role in the pathogenesis of ischemic MR, through a novel mechanism: atriogenic leaflet tethering. When ischemic MR is hemodynamically significant, the left ventricle compensates by dilating to preserve forward output using the Starling mechanism. Left ventricular dilatation, however, worsens MR by increasing the mitral valve regurgitant orifice, leading to a vicious cycle in which MR begets more MR. The author proposes that several structural adaptations play a role in reducing ischemic MR. In contrast to the compensatory effects of left ventricular enlargement, these may reduce, rather than increase, its severity. The suggested adaptations involve the mitral valve leaflets, the papillary muscles, the mitral annulus, and the left ventricular false tendons. This review describes the potential role each may play in reducing ischemic MR. Therapies that exploit these adaptations are also discussed.

  7. Ischemic stroke patients are biologically older than their chronological age

    PubMed Central

    Soriano-Tárraga, Carolina; Giralt-Steinhauer, Eva; Mola-Caminal, Marina; Vivanco-Hidalgo, Rosa M.; Ois, Angel; Rodríguez-Campello, Ana; Cuadrado-Godia, Elisa; Sayols-Baixeras, Sergi; Elosua, Roberto; Roquer, Jaume; Jiménez-Conde, Jordi

    2016-01-01

    Ischemic stroke is associated with aging. It is possible to predict chronological age by measuring age-related changes in DNA methylation from multiple CpG sites across the genome, known as biological age. The difference between biological age and actual chronological age would indicate an individual's level of aging. Our aim was to determine the biological age of ischemic stroke patients and compare their aging with controls of the same chronological age. A total of 123 individuals, 41 controls and 82 patients with ischemic stroke were paired by chronological age, ranging from 39 to 82 years. Illumina HumanMethylation450 BeadChip array was used to measure DNA methylation in CpG sites in both groups, and biological age was estimated using methylation values of specific CpGs. Ischemic stroke patients were biologically an average 2.5 years older than healthy controls (p-value=0.010). Stratified by age tertiles, younger stroke patients (≤57 years old) were biologically older than controls (OR=1.19; 95%CI 1.00-1.41, p-value=0.046). The older groups showed no biological age differences between cases and controls, but were close to reaching the significance level. Ischemic stroke patients are biologically older than controls. Biological age should be considered as a potential new biomarker of stroke risk. PMID:27922817

  8. Potential microRNA biomarkers for acute ischemic stroke.

    PubMed

    Zeng, Ye; Liu, Jing-Xia; Yan, Zhi-Ping; Yao, Xing-Hong; Liu, Xiao-Heng

    2015-12-01

    Acute ischemic stroke is a significant cause of high morbidity and mortality in the aging population globally. However, current therapeutic strategies for acute ischemic stroke are limited. Atherosclerotic plaque is considered an independent risk factor for acute ischemic stroke. To identify biomarkers for carotid atheromatous plaque, bioinformatics analysis of the gene microarray data of plaque and intact tissue from individuals was performed. Differentially expressed genes (DEGs) were identified using the Multtest and Limma packages of R language, including 56 downregulated and 69 upregulated DEGs. Enriched microRNA (miRNA or miR) DEGs networks were generated using WebGestalt software and the STRING databases, and the miRNAs were validated using serum from acute ischemic stroke patients with reverse transcription quantitative PCR (RT‑qPCR). Four confirmed differentially expressed miRNAs (miR‑9, ‑22, ‑23 and ‑125) were associated with 28 upregulated DEGs, and 7 miRNAs (miR‑9, ‑30, ‑33, ‑124, ‑181, ‑218 and ‑330) were associated with 25 downregulated DEGs. Gene ontology (GO) function suggested that the confirmed miRNA‑targeted DEGs predominantly associated with signal transduction, the circulatory system, biological adhesion, striated muscle contraction, wound healing and the immune system. The confirmed miRNA‑targeted genes identified serve as potential therapeutic targets for acute ischemic stroke.

  9. Migraine prophylaxis, ischemic depolarizations, and stroke outcomes in mice.

    PubMed

    Eikermann-Haerter, Katharina; Lee, Jeong Hyun; Yalcin, Nilufer; Yu, Esther S; Daneshmand, Ali; Wei, Ying; Zheng, Yi; Can, Anil; Sengul, Buse; Ferrari, Michel D; van den Maagdenberg, Arn M J M; Ayata, Cenk

    2015-01-01

    Migraine with aura is an established stroke risk factor, and excitatory mechanisms such as spreading depression (SD) are implicated in the pathogenesis of both migraine and stroke. Spontaneous SD waves originate within the peri-infarct tissue and exacerbate the metabolic mismatch during focal cerebral ischemia. Genetically enhanced SD susceptibility facilitates anoxic depolarizations and peri-infarct SDs and accelerates infarct growth, suggesting that susceptibility to SD is a critical determinant of vulnerability to ischemic injury. Because chronic treatment with migraine prophylactic drugs suppresses SD susceptibility, we tested whether migraine prophylaxis can also suppress ischemic depolarizations and improve stroke outcome. We measured the cortical susceptibility to SD and ischemic depolarizations, and determined tissue and neurological outcomes after middle cerebral artery occlusion in wild-type and familial hemiplegic migraine type 1 knock-in mice treated with vehicle, topiramate or lamotrigine daily for 7 weeks or as a single dose shortly before testing. Chronic treatment with topiramate or lamotrigine reduced the susceptibility to KCl-induced or electric stimulation-induced SDs as well as ischemic depolarizations in both wild-type and familial hemiplegic migraine type 1 mutant mice. Consequently, both tissue and neurological outcomes were improved. Notably, treatment with a single dose of either drug was ineffective. These data underscore the importance of hyperexcitability as a mechanism for increased stroke risk in migraineurs, and suggest that migraine prophylaxis may not only prevent migraine attacks but also protect migraineurs against ischemic injury. © 2014 American Heart Association, Inc.

  10. Ischemic contracture of the left ventricle. Production and prevention.

    PubMed

    MacGregor, D C; Wilson, G J; Tanaka, S; Holness, D E; Lixfeld, W; Silver, M D; Rubis, L J; Goldstein, W; Gunstensen, J; Bigelow, W G

    1975-12-01

    Ischemic contracture of the left ventricle ("stone heart") is a recognized complication of prolonged periods of interruption of the coronary circulation during open-heart surgery. We have examined the effects of moderate hypothermia (28 degrees C.) and preoperative beta-adrenergic blockade (propranolol, 0.5 mg. per kilogram; 1.0 mg. per kilogram) on contracture development during ischemic arrest of the heart. Four groups of 8 dogs each were placed on total cardiopulmonary bypass, and ischemic arrest of the heart was produced by cross-clamping the ascending aorta and venting the left ventricle. Intramyocardial carbon dioxide tension was continuously monitored by mass spectrometry. When anaerobic energy production ceased, as indicated by a final plateau in the intramyocardial carbon dioxide accumulation curve, the ischemic arrest was terminated and the contractile state of the heart observed. These results are given in the text. We conclude that beta-adrenergic blockade delays, but does not prevent, the onset of ischemic contracture of the left ventricle under normothermic conditions. Moderate hypothermia appears to prevent this complication completely.

  11. Management of Acute Hypertensive Response in Patients With Ischemic Stroke

    PubMed Central

    Qureshi, Adnan I.

    2016-01-01

    High blood pressure (BP) >140/90 mm Hg is seen in 75% of patients with acute ischemic stroke and in 80% of patients with acute intracerebral hemorrhages and is independently associated with poor functional outcome. While BP reduction in patients with chronic hypertension remains one of the most important factors in primary and secondary stroke prevention, the proper management strategy for acute hypertensive response within the first 72 hours of acute ischemic stroke has been a matter of debate. Recent guidelines recommend clinical trials to ascertain whether antihypertensive therapy in the acute phase of stroke is beneficial. This review summarizes the current data on acute hypertensive response or elevated BP management during the first 72 hours after an acute ischemic stroke. Based on the potential deleterious effect of lowering BP observed in some clinical trials in patients with acute ischemic stroke and because of the lack of convincing evidence to support acute BP lowering in those situations, aggressive BP reduction in patients presenting with acute ischemic stroke is currently not recommended. While the early use of angiotensin receptor antagonists may help reduce cardiovascular events, this benefit is not necessarily related to BP reduction. PMID:27366297

  12. Pharmaceutical sponsorship bias influences thrombolytic literature in acute ischemic stroke.

    PubMed

    Radecki, Ryan Patrick

    2011-11-01

    The efficacy of thrombolytic therapy for acute ischemic stroke remains controversial in emergency medicine and has not been fully endorsed by either the American College of Emergency Physicians or the American Academy of emergency medicine. A growing recognition exists of the influence of pharmaceutical sponsorship on the reported findings of published clinical trials. Sponsorship bias has been suggested as a potential criticism of the literature and guidelines favoring thrombolytic therapy. The objective of this study is to review the most influential literature regarding thrombolytic therapy for acute ischemic stroke and document the presence or absence of pharmaceutical sponsorship. A publication-citation analysis was performed to identify the most frequently cited articles pertaining to thrombolytic therapy for acute ischemic stroke. Identified articles were reviewed for disclosures of pharmaceutical funding. Of the 20 most-cited articles pertaining to thrombolytic therapy for acute stroke, 17 (85%) disclosed pharmaceutical sponsorship. These disclosures range from general sponsorship to direct employment of authors by pharmaceutical companies. An overwhelming predominance of the most influential literature regarding thrombolytic therapy for acute ischemic stroke is susceptible to sponsorship bias. This potential bias may provide a basis for physician concern regarding the efficacy and safety of thrombolytic therapy. Further, large, independent, placebo-controlled studies may be required to guide therapy and professional guidelines definitively for acute ischemic stroke.

  13. Pharmaceutical Sponsorship Bias Influences Thrombolytic Literature in Acute Ischemic Stroke

    PubMed Central

    Radecki, Ryan Patrick

    2011-01-01

    Background The efficacy of thrombolytic therapy for acute ischemic stroke remains controversial in emergency medicine and has not been fully endorsed by either the American College of Emergency Physicians or the American Academy of emergency medicine. A growing recognition exists of the influence of pharmaceutical sponsorship on the reported findings of published clinical trials. Sponsorship bias has been suggested as a potential criticism of the literature and guidelines favoring thrombolytic therapy. Objective The objective of this study is to review the most influential literature regarding thrombolytic therapy for acute ischemic stroke and document the presence or absence of pharmaceutical sponsorship. Methods A publication-citation analysis was performed to identify the most frequently cited articles pertaining to thrombolytic therapy for acute ischemic stroke. Identified articles were reviewed for disclosures of pharmaceutical funding. Results Of the 20 most-cited articles pertaining to thrombolytic therapy for acute stroke, 17 (85%) disclosed pharmaceutical sponsorship. These disclosures range from general sponsorship to direct employment of authors by pharmaceutical companies. Conclusion An overwhelming predominance of the most influential literature regarding thrombolytic therapy for acute ischemic stroke is susceptible to sponsorship bias. This potential bias may provide a basis for physician concern regarding the efficacy and safety of thrombolytic therapy. Further, large, independent, placebo-controlled studies may be required to guide therapy and professional guidelines definitively for acute ischemic stroke. PMID:22224134

  14. Xanthine oxidase inhibition attenuates ischemic-reperfusion lung injury

    SciTech Connect

    Lynch, M.J.; Grum, C.M.; Gallagher, K.P.; Bolling, S.F.; Deeb, G.M.; Morganroth, M.L.

    1988-05-01

    Ischemic-reperfusion lung injury is a factor potentially limiting the usefulness of distant organ procurement for heart-lung transplantation. Toxic oxygen metabolites are considered a major etiologic factor in reperfusion injury. Although oxygen-free radicals may be generated by many mechanisms, we investigated the role of xanthine oxidase in this injury process by using lodoxamide, a xanthine oxidase inhibitor, to inhibit ischemic-reperfusion injury in an isolated rat lung model. Isolated rat lungs were perfused with physiologic salt solution (PSS) osmotically stabilized with Ficoll until circulating blood elements were nondetectable in the pulmonary venous effluent. Lungs were rendered ischemic by interrupting ventilation and perfusion for 2 hr at 37/sup 0/C. After the ischemic interval, the lungs were reperfused with whole blood and lung injury was determined by measuring the accumulation of /sup 125/I-bovine serum albumin in lung parenchyma and alveolar lavage fluid as well as by gravimetric measurements. Lung effluent was collected immediately pre- and postischemia for analysis of uric acid by high-pressure liquid chromatography. Lodoxamide (1 mM) caused significant attenuation of postischemic lung injury. Uric acid levels in the lung effluent confirmed inhibition of xanthine oxidase. Protection from injury was not complete, however, implying that additional mechanisms may contribute to ischemic-reperfusion injury in the lung.

  15. Expression of Alzheimer's disease risk genes in ischemic brain degeneration.

    PubMed

    Ułamek-Kozioł, Marzena; Pluta, Ryszard; Januszewski, Sławomir; Kocki, Janusz; Bogucka-Kocka, Anna; Czuczwar, Stanisław J

    2016-12-01

    We review the Alzheimer-related expression of genes following brain ischemia as risk factors for late-onset of sporadic Alzheimer's disease and their role in Alzheimer's disease ischemia-reperfusion pathogenesis. More recent advances in understanding ischemic etiology of Alzheimer's disease have revealed dysregulation of Alzheimer-associated genes including amyloid protein precursor, β-secretase, presenilin 1 and 2, autophagy, mitophagy and apoptosis. We review the relationship between these genes dysregulated by brain ischemia and the cellular and neuropathological characteristics of Alzheimer's disease. Here we summarize the latest studies supporting the theory that Alzheimer-related genes play an important role in ischemic brain injury and that ischemia is a needful and leading supplier to the onset and progression of sporadic Alzheimer's disease. Although the exact molecular mechanisms of ischemic dependent neurodegenerative disease and neuronal susceptibility finally are unknown, a downregulated expression of neuronal defense genes like alfa-secretase in the ischemic brain makes the neurons less able to resist injury. The recent challenge is to find ways to raise the adaptive reserve of the brain to overcome such ischemic-associated deficits and support and/or promote neuronal survival. Understanding the mechanisms underlying the association of these genes with risk for Alzheimer's disease will provide the most meaningful targets for therapeutic development to date.

  16. THROMBOLYTIC THERAPY FOR ACUTE ISCHEMIC STROKE BEYOND THREE HOURS

    PubMed Central

    Carpenter, Christopher R.; Keim, Samuel M.; Milne, William Kenneth; Meurer, William J.; Barsan, William G.

    2011-01-01

    Background Ischemic cerebrovascular accidents remain a leading cause of morbidity and mortality. Thrombolytic therapy for acute ischemic stroke within 3 h of symptom onset of highly select patients has been advocated by some groups since 1995, but trials have yielded inconsistent outcomes. One recent trial demonstrated significant improvement when the therapeutic window was extended to 4.5 h. Clinical Question Does the intravenous systemic administration of tPA within 4.5 h to select patients with acute ischemic stroke improve functional outcomes? Evidence Review All randomized controlled trials enrolling patients within 4.5 h were identified, in addition to a meta-analysis of these trial data. Results The National Institute of Neurological Disorders and Stroke (NINDS) and European Cooperative Acute Stroke Study III (ECASS III) clinical trials demonstrated significantly improved outcomes at 3 months, with increased rates of intracranial hemorrhage, whereas ECASS II and the Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study showed increased hemorrhagic complications without improving outcomes. Meta-analysis of trial data from all ECASS trials, NINDS, and ATLANTIS suggest that thrombolysis within 4.5 h improves functional outcomes. Conclusion Ischemic stroke tPA treatment within 4.5 h seems to improve functional outcomes and increases symptomatic intracranial hemorrhage rates without significantly increas ing mortality. PMID:20576390

  17. Lung Function Abnormalities in Smokers with Ischemic Heart Disease.

    PubMed

    Franssen, Frits M E; Soriano, Joan B; Roche, Nicolas; Bloomfield, Paul H; Brusselle, Guy; Fabbri, Leonardo M; García-Rio, Francisco; Kearney, Mark T; Kwon, Namhee; Lundbäck, Bo; Rabe, Klaus F; Raillard, Alice; Muellerova, Hana; Cockcroft, John R

    2016-09-01

    The aim of the ALICE (Airflow Limitation in Cardiac Diseases in Europe) study was to investigate the prevalence of airflow limitation in patients with ischemic heart disease and the effects on quality of life, healthcare use, and future health risk. To examine prebronchodilator and post-bronchodilator spirometry in outpatients aged greater than or equal to 40 years with clinically documented ischemic heart disease who were current or former smokers. This multicenter, cross-sectional study was conducted in 15 cardiovascular outpatient clinics in nine European countries. Airflow limitation was defined as post-bronchodilator FEV1/FVC less than 0.70. Among the 3,103 patients with ischemic heart disease who were recruited, lung function was defined for 2,730 patients. Airflow limitation was observed in 30.5% of patients with ischemic heart disease: 11.3% had mild airflow limitation, 15.8% moderate airflow limitation, 3.3% severe airflow limitation, and 0.1% very severe airflow limitation. Most patients with airflow limitation (70.6%) had no previous spirometry testing or diagnosed pulmonary disease. Airflow limitation was associated with greater respiratory symptomatology, impaired health status, and more frequent emergency room visits (P < 0.05). Airflow limitation compatible with chronic obstructive pulmonary disease affects almost one-third of patients with ischemic heart disease. Although airflow limitation is associated with additional morbidity and societal burden, it is largely undiagnosed and untreated. Clinical trial registered with www.clinicaltrials.gov (NCT 01485159).

  18. Management of Acute Hypertensive Response in Patients With Ischemic Stroke.

    PubMed

    AlSibai, Ahmad; Qureshi, Adnan I

    2016-07-01

    High blood pressure (BP) >140/90 mm Hg is seen in 75% of patients with acute ischemic stroke and in 80% of patients with acute intracerebral hemorrhages and is independently associated with poor functional outcome. While BP reduction in patients with chronic hypertension remains one of the most important factors in primary and secondary stroke prevention, the proper management strategy for acute hypertensive response within the first 72 hours of acute ischemic stroke has been a matter of debate. Recent guidelines recommend clinical trials to ascertain whether antihypertensive therapy in the acute phase of stroke is beneficial. This review summarizes the current data on acute hypertensive response or elevated BP management during the first 72 hours after an acute ischemic stroke. Based on the potential deleterious effect of lowering BP observed in some clinical trials in patients with acute ischemic stroke and because of the lack of convincing evidence to support acute BP lowering in those situations, aggressive BP reduction in patients presenting with acute ischemic stroke is currently not recommended. While the early use of angiotensin receptor antagonists may help reduce cardiovascular events, this benefit is not necessarily related to BP reduction.

  19. Metabolic Syndrome in Polish Ischemic Stroke Patients.

    PubMed

    Brola, Waldemar; Sobolewski, Piotr; Fudala, Małgorzata; Goral, Anna; Kasprzyk, Marta; Szczuchniak, Wiktor; Pejas-Dulewicz, Renata; Przybylski, Wojciech

    2015-09-01

    Metabolic syndrome (MetS) predisposes individuals to cardiovascular disease or stroke development. We aimed at evaluating the prevalence of MetS in a population of acute ischemic stroke (IS) patients from central Poland and at estimating the relationship between MetS and stroke risk. We analyzed 672 IS patients who were consecutively admitted to stroke units. The control group was composed of 612 patients with other neurologic disorders. MetS was diagnosed if 3 of 5 factors were present (obesity, increased blood pressure, increased triglycerides, low high-density lipoprotein [HDL] cholesterol, and fasting hyperglycemia) according to the Unified Criteria for Clinical Diagnosis of the Metabolic Syndrome (2009). MetS was diagnosed in 61.2% of stroke patients versus 18.1% of the control group (P < .001). Multiple logistic regression showed that MetS was 1.8 times more common in women than in men (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.4-2.5). The adjusted OR (95% CI) associated with MetS was 2.44 (1.48-3.64; P < .001) for IS. Hypertension and hypertriglyceridemia were the most frequent disturbances of IS patients (87.2% and 68.2%, respectively). The analysis of the interaction between MetS and its components showed significant associations with hypertension (OR, 2.15; 95% CI, .98-4.24; P < .01), high triglyceride levels (OR, 4.35; 95% CI, 2.87-9.43; P < .0001), and low HDL cholesterol levels (OR, 5.12; 95% CI, 3.15-8.20; P < .001). Over 60% of Polish IS patients have MetS. The prevalence of MetS was significantly higher in women than in men. Thus, MetS may be a risk factor for IS. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. Heart Failure in Acute Ischemic Stroke

    PubMed Central

    Cuadrado-Godia, Elisa; Ois, Angel; Roquer, Jaume

    2010-01-01

    Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Due to the aging of the population it has become a growing public health problem in recent decades. Diagnosis of HF is clinical and there is no diagnostic test, although some basic complementary testing should be performed in all patients. Depending on the ejection fraction (EF), the syndrome is classified as HF with low EF or HF with normal EF (HFNEF). Although prognosis in HF is poor, HFNEF seems to be more benign. HF and ischemic stroke (IS) share vascular risk factors such as age, hypertension, diabetes mellitus, coronary artery disease and atrial fibrillation. Persons with HF have higher incidence of IS, varying from 1.7% to 10.4% per year across various cohort studies. The stroke rate increases with length of follow-up. Reduced EF, independent of severity, is associated with higher risk of stroke. Left ventricular mass and geometry are also related with stroke incidence, with concentric hypertrophy carrying the greatest risk. In HF with low EF, the stroke mechanism may be embolism, cerebral hypoperfusion or both, whereas in HFNEF the mechanism is more typically associated with chronic endothelial damage of the small vessels. Stroke in patients with HF is more severe and is associated with a higher rate of recurrence, dependency, and short term and long term mortality. Cardiac morbidity and mortality is also high in these patients. Acute stroke treatment in HF includes all the current therapeutic options to more carefully control blood pressure. For secondary prevention, optimal control of all vascular risk factors is essential. Antithrombotic therapy is mandatory, although the choice of a platelet inhibitor or anticoagulant drug depends on the cardiac disease. Trials are ongoing to evaluate anticoagulant therapy for prevention of embolism in patients with low EF who are at

  1. ISCHEMIC MODEL OF OPTIC NERVE INJURY

    PubMed Central

    Cioffi, George A

    2005-01-01

    Purpose It is proposed that the anterior optic nerve is specifically susceptible to microcirculatory compromise contributing to the development of glaucomatous optic neuropathy. Methods Ischemic optic neuropathy was induced by delivering endothelin-1 (ET-1) to the retrobulbar space in one eye of 12 primates for 6 to 12 months. Regional ganglion cell axonal sizes and densities were compared with the normal, contralateral eyes. Results Without changes of intraocular pressure, mean axonal density was significantly decreased in ET-1 eyes compared to controls (P = .03, paired t test). Two-way matched-pair analysis of variance showed a significant effect of ET-1 on overall axonal density (P < .0001). Among the animals with significant axonal loss, the mean axonal loss was 11.6%, and loss varied from 4% to 21%. Axonal loss was commonly localized within specific quadrants. Five animals were examined for preferential axonal size loss. As a group, there appears to be a tendency toward preferential large axonal loss, but the mean axonal loss of large and small axons did not meet significant differences (P = .1) However, examination of individual animals with significant loss shows significantly greater loss of large axons as compared to the small axons in three of the animals. Conclusions Chronic optic nerve ischemia causes demonstrable and localized damage of the optic nerve, without intraocular pressure elevation. There is preferential loss of large retinal ganglion cell axons in animals with significant axonal loss. Ischemia-induced focal axonal loss is similar to human glaucoma and may represent a differential regional vulnerability. PMID:17057819

  2. Bone Fracture Exacerbates Murine Ischemic Cerebral Injury

    PubMed Central

    Degos, Vincent; Maze, Mervyn; Vacas, Susana; Hirsch, Jan; Guo, Yi; Shen, Fanxia; Jun, Kristine; van Rooijen, Nico; Gressens, Pierre; Young, William L.; Su, Hua

    2014-01-01

    Background Bone fracture increases alarmins and pro-inflammatory cytokines in the blood, and provokes macrophage infiltration and pro-inflammatory cytokine expression in the hippocampus. We recently reported that stroke is an independent risk factor after bone surgery for adverse outcome, the impact of bone fracture on stroke outcome is unknown. We tested the hypothesis that bone fracture, shortly after ischemic stroke, enhances stroke-related injuries by augmenting the neuroinflammatory response. Methods Tibia fracture (bone fracture) was induced in mice one day after permanent occlusion of the distal middle cerebral artery (stroke). High-mobility-group box chromosomal protein-1 (HMGB1) was tested to mimic the bone fracture effects. HMGB1 neutralizing antibody and clodrolip (macrophage depletion) were tested to attenuate the bone fracture effects. Neurobehavioral function (n=10), infarct volume, neuronal death, and macrophages/microglia-infiltration (n=6–7) were analyzed three days after. Results We found that mice with both stroke and bone fracture had larger infarct volumes (mean percentage of ipsilateral hemisphere±SD: 30±7% vs. 12±3%, n=6, P<0.001) more severe neurobehavioral dysfunction, and more macrophages/microglia in the peri-infarct region than mice with stroke only. Intraperitoneal injection of HMGB1 mimicked, whereas neutralizing HMGB1 attenuated, the bone fracture effects and the macrophage/microglia infiltration. Depleting macrophages with clodrolip also attenuated the aggravating effects of bone fracture on stroke lesion and behavioral dysfunction. Conclusions These novel findings suggest that bone fracture shortly after stroke enhances stroke injury via augmented inflammation through HMGB1 and macrophage/microglia infiltration. Interventions to modulate early macrophage/microglia activation could be therapeutic goals to limit the adverse consequences of bone fracture after stroke. PMID:23438676

  3. Morinda citrifolia fruit juice prevents ischemic neuronal damage through suppression of the development of post-ischemic glucose intolerance.

    PubMed

    Harada, Shinichi; Fujita-Hamabe, Wakako; Kamiya, Kohei; Mizushina, Yoshiyuki; Satake, Toshiko; Tokuyama, Shogo

    2010-10-01

    Fruit juice of Morinda citrifolia (Noni juice) is a well-known health drink and has various pharmacological properties including antioxidant and anti-inflammatory effects. We have hitherto found the protective effect of Noni juice on brain damage caused by ischemic stress in mice. In addition, we also recently reported that regulation of post-ischemic glucose intolerance might be important for good prognosis. Here, we focused on the effect of Noni juice on the development of the post-ischemic glucose intolerance as a cerebral protective mechanism. Noni juice was obtained from the mature fruit grown in Okinawa (about 1.5 L/4 kg of fruit; 100% ONJ). Male ddY mice were given 10% ONJ in drinking water for 7 days. Then, mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Ingestion of 10% ONJ suppressed the development of neuronal damage after MCAO. Interestingly, glucose intolerance observed on the 1st day after MCAO completely disappeared after 10% ONJ administration. Furthermore, ONJ treatment significantly increased serum insulin levels much further than the control group on the 1st day, while serum adiponectin levels were not affected at all. These results suggest that ONJ could facilitate insulin secretion after ischemic stress and may attenuate the development of glucose intolerance. These mechanisms may contribute to the neuronal protective effect of ONJ against ischemic stress.

  4. Detection of atrial fibrillation with concurrent holter monitoring and continuous cardiac telemetry following ischemic stroke and transient ischemic attack.

    PubMed

    Lazzaro, Marc A; Krishnan, Kousik; Prabhakaran, Shyam

    2012-02-01

    Atrial fibrillation (AF) is a major risk factor for recurrent ischemic stroke. We aimed to compare the detection rate of AF using continuous cardiac telemetry (CCT) versus Holter monitoring in hospitalized patients with ischemic stroke or transient ischemic attack (TIA). Between June 2007 and December 2008, 133 patients were admitted to an academic institution for ischemic stroke or TIA and underwent concurrent inpatient CCT and Holter monitoring. Rates of AF detection by CCT and Holter monitoring were compared using the McNemar paired proportion test. Among the 133 patients, 8 (6.0%) were diagnosed with new-onset AF. On average, Holter monitoring was performed for 29.8 hours, and CCT was performed for 73.6 hours. The overall rate of AF detection was higher for Holter monitoring compared with CCT (6.0%; 95% confidence interval [CI], 2.9-11.6 vs 0; 95% CI, 0-3.4; P = .008). Holter detection of AF was even higher in specific subgroups (those with an embolic infarct pattern, those age >65 years, and those with coronary artery disease). Holter monitoring detected AF in 6% of hospitalized ischemic stroke and TIA patients, with higher proportions in high-risk subgroups. Compared with CCT, Holter monitoring is significantly more likely to detect arrhythmias. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. Depression: links with ischemic heart disease and erectile dysfunction.

    PubMed

    Roose, Steven P

    2003-01-01

    This article examines the relationships among depression, ischemic heart disease, and erectile dysfunction. Depression is an independent risk factor for the development of ischemic heart disease, and depression in the post-myocardial infarction patient is associated with increased morbidity and mortality. Ischemic heart disease and erectile dysfunction are also frequently comorbid and share many common risk factors including age, hypertension, diabetes, dyslipidemia, obesity, sedentary lifestyle, and smoking. Depression and erectile dysfunction often occur together; however, the causal relation may be difficult to determine because erectile dysfunction may be a symptom of depression, social distress accompanying erectile dysfunction may precipitate depressive symptoms, or both conditions may result from a common factor such as vascular disease.

  6. [Perception of emotions in patients with ischemic stroke].

    PubMed

    Nikishina, V B; Petrash, E A; Zapesotskaya, I V

    2015-01-01

    To study neuropsychological characteristics of perception processes, recognition and differentiation of emotional distress in post stroke patients with regard to localization of ischemic lesion. Authors examined 47 post stroke patients with right-hemisphere and left hemisphere localization of ischemic stroke in the early stage of hospitalization. The Subjective Feelings Scale and a battery of neuropsychological tests were used. In patients with right-hemisphere localization of the lesion, positive emotional reactions were more frequent, neuropsychological implementation level was realized through details and differentiation of the image. In patients with left-hemispheric localization of ischemic stroke, negative emotional reactions were dominated and neuropsychological implementation level was realized through a vague and undifferentiated way.

  7. Intermittent fasting attenuates inflammasome activity in ischemic stroke.

    PubMed

    Fann, David Yang-Wei; Santro, Tomislav; Manzanero, Silvia; Widiapradja, Alexander; Cheng, Yi-Lin; Lee, Seung-Yoon; Chunduri, Prasad; Jo, Dong-Gyu; Stranahan, Alexis M; Mattson, Mark P; Arumugam, Thiruma V

    2014-07-01

    Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Persimmon leaf flavonoid induces brain ischemic tolerance in mice☆

    PubMed Central

    Miao, Mingsan; Zhang, Xuexia; Wang, Linan

    2013-01-01

    The persimmon leaf has been shown to improve cerebral ischemic outcomes; however, its mechanism of action remains unclear. In this study, mice were subjected to 10 minutes of ischemic preconditioning, and persimmon leaf flavonoid was orally administered for 5 days. Results showed that the persimmon leaf flavonoid significantly improved the content of tissue type plasminogen activator and 6-keto prostaglandin-F1 α in the cerebral cortex, decreased the content of thromboxane B2, and reduced the content of plasminogen activator inhibitor-1 in mice. Following optical microscopy, persimmon leaf flavonoid was also shown to reduce cell swelling and nuclear hyperchromatism in the cerebral cortex and hippocampus of mice. These results suggested that persimmon leaf flavonoid can effectively inhibit brain thrombosis, improve blood supply to the brain, and relieve ischemia-induced pathological damage, resulting in brain ischemic tolerance. PMID:25206432

  9. Ischemic retinopathy associated with Crohn’s disease

    PubMed Central

    Siqueira, Rubens Camargo; Kaiser Junior, Roberto Luiz; Ruiz, Lilian Piron; Ruiz, Milton Arthur

    2016-01-01

    Purpose To report a case of a patient with ischemic retinopathy associated with Crohn’s disease. Case report This report presents a case of a 28-year-old female patient with Crohn’s disease and sudden decrease of visual acuity in the right eye. Fluorescein angiography, optical coherence tomography, and multifocal electroretinography confirmed the clinical features of ischemic retinopathy. After systemic corticosteroid treatment, the patient developed epiretinal membrane without significant improvement in visual acuity. Discussion The patient presented with ischemic retinopathy associated with Crohn’s disease with deficiency of central visual acuity. Periodic examination by a retina specialist is recommended for patients being treated for Crohn’s disease. PMID:27524921

  10. Stroke intervention: catheter-based therapy for acute ischemic stroke.

    PubMed

    White, Christopher J; Abou-Chebl, Alex; Cates, Christopher U; Levy, Elad I; McMullan, Paul W; Rocha-Singh, Krishna; Weinberger, Jesse M; Wholey, Mark H

    2011-07-05

    The majority (>80%) of the three-quarters of a million strokes that will occur in the United States this year are ischemic in nature. The treatment of acute ischemic stroke is very similar to acute myocardial infarction, which requires timely reperfusion therapy for optimal results. The majority of patients with acute ischemic stroke do not receive any form of reperfusion therapy, unlike patients with acute myocardial infarction. Improving outcomes for acute stroke will require patient education to encourage early presentation, an aggressive expansion of qualified hospitals, and willing providers and early imaging strategies to match patients with their best options for reperfusion therapy to minimize complications. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population.

    PubMed

    Varbo, Anette; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne; Schnohr, Peter; Jensen, Gorm B; Benn, Marianne

    2011-04-01

    Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population. A total of 7,579 women and 6,372 men from the Copenhagen City Heart Study with measurements of nonfasting triglycerides and cholesterol at baseline in 1976-1978 were followed for up to 33 years; of these, 837 women and 837 men developed ischemic stroke during follow-up, which was 100% complete. The fluctuation of nonfasting triglycerides and cholesterol over 15 years was similar. In both women and men, stepwise increasing levels of nonfasting triglycerides were associated with increased risk of ischemic stroke. Compared to women with triglycerides <1 mmol/liter, multivariate adjusted hazard ratios ranged from 1.2 (95% confidence interval [CI], 0.9-1.7) for triglyceride levels of 1.00-1.99 mmol/liter to 3.9 (95%CI, 1.3-11.1) for triglyceride levels ≥ 5 mmol/liter (trend: p < 0.001); corresponding hazard ratios in men ranged from 1.2 (95%CI, 0.8-1.7) to 2.3 (95%CI, 1.2-4.3) (p = 0.001). Increasing cholesterol levels were not associated with risk of ischemic stroke except in men with cholesterol levels ≥ 9.00 mmol/liter vs < 5.00 mmol/liter, with a hazard ratio of 4.4 (95%CI, 1.9-10.6). In women, stepwise increasing levels of nonfasting triglycerides were associated with increasing risk of ischemic stroke while increasing cholesterol levels were not. In men, these results were similar except that cholesterol ≥ 9.00 mmol/liter was associated with increased risk of ischemic stroke. Copyright © 2011 American Neurological Association.

  12. IL1RN VNTR Polymorphism in Ischemic Stroke

    PubMed Central

    Worrall, Bradford B.; Brott, Thomas G.; Brown, Robert D.; Brown, W. Mark; Rich, Stephen S.; Arepalli, Sampath; Wavrant-De Vrièze, Fabienne; Duckworth, Jaime; Singleton, Andrew B.; Hardy, John; Meschia, James F.

    2008-01-01

    Background and Purpose Genetic factors influence risk for ischemic stroke and likely do so at multiple steps in the pathogenic process. Variants in genes related to inflammation contribute to risk of stroke. The purpose of this study was to confirm our earlier finding of an association between allele 2 of a variable number tandem repeat of the IL-1 receptor antagonist gene (IL1RN) and cerebrovascular disease. Methods An association study of the variable number tandem repeat genotype with ischemic stroke and stroke subtypes was performed on samples from a North American study of affected sibling pairs concordant for ischemic stroke and 2 North American cohorts of prospectively ascertained ischemic stroke cases and unrelated controls. DNA analysis was performed on cases and controls, stratified by race. Results After adjustment for age, sex, and stroke risk factors, the odds ratio for association of allele 2 and ischemic stroke was 2.80 (95% confidence interval, 1.29 to 6.11; P=0.03) for the white participants. The effect of allele 2 of IL1RN on stroke risk most closely fits a recessive genetic model (P=0.009). For the smaller sample of nonwhite participants, the results were not significant. Conclusions Allele 2 of IL1RN, present in nearly one-quarter of stroke patients, may contribute to genetic risk for ischemic stroke and confirm the previously identified association with cerebrovascular disease. These results are driven by the association in the white participants. Further exploration in a larger nonwhite sample is warranted. PMID:17332449

  13. Moderate alcohol intake reduces risk of ischemic stroke in Korea

    PubMed Central

    Lee, Soo Joo; Cho, Yong-Jin; Kim, Jae Guk; Ko, Youngchai; Hong, Keun-Sik; Park, Jong-Moo; Kang, Kyusik; Park, Tai Hwan; Park, Sang-Soon; Lee, Kyung Bok; Cha, Jae Kwan; Kim, Dae-Hyun; Lee, Jun; Kim, Joon-Tae; Lee, Juneyoung; Lee, Ji Sung; Jang, Myung Suk; Han, Moon-Ku; Gorelick, Philip B.

    2015-01-01

    Objective: We undertook a population-based, case-control study to examine a dose-response relationship between alcohol intake and risk of ischemic stroke in Koreans who had different alcoholic beverage type preferences than Western populations and to examine the effect modifications by sex and ischemic stroke subtypes. Methods: Cases (n = 1,848) were recruited from patients aged 20 years or older with first-ever ischemic stroke. Stroke-free controls (n = 3,589) were from the fourth and fifth Korean National Health and Nutrition Examination Survey and were matched to the cases by age (±3 years), sex, and education level. All participants completed an interview using a structured questionnaire about alcohol intake. Results: Light to moderate alcohol intake, 3 or 4 drinks (1 drink = 10 g ethanol) per day, was significantly associated with a lower odds of ischemic stroke after adjusting for potential confounders (no drinks: reference; <1 drink: odds ratio 0.38, 95% confidence interval 0.32–0.45; 1–2 drinks: 0.45, 0.36–0.57; and 3–4 drinks: 0.54, 0.39–0.74). The threshold of alcohol effect in women was slightly lower than that in men (up to 1–2 drinks in women vs up to 3–4 drinks in men), but this difference was not statistically significant. There was no statistical interaction between alcohol intake and the subtypes of ischemic stroke (p = 0.50). The most frequently used alcoholic beverage was one native to Korea, soju (78% of the cases), a distilled beverage with 20% ethanol by volume. Conclusions: Our findings suggest that light to moderate distilled alcohol consumption may reduce the risk of ischemic stroke in Koreans. PMID:26519539

  14. Ischemic preconditioning of one forearm enhances static and dynamic apnea.

    PubMed

    Kjeld, Thomas; Rasmussen, Mads Reinholdt; Jattu, Timo; Nielsen, Henning Bay; Secher, Niels Henry

    2014-01-01

    Ischemic preconditioning enhances ergometer cycling and swimming performance. We evaluated whether ischemic preconditioning of one forearm (four times for 5 min) also affects static breath hold and underwater swimming, whereas the effect of similar preconditioning on ergometer rowing served as control because the warm-up for rowing regularly encompasses intense exercise and therefore reduced muscle oxygenation. Six divers performed a dry static breath hold, 11 divers swam underwater in an indoor pool, and 14 oarsmen rowed "1000 m" on an ergometer. Ischemic preconditioning reduced the forearm oxygen saturation from 65% ± 7% to 19% ± 7% (mean ± SD; P < 0.001), determined using spatially resolved near-infrared spectroscopy. During the breath hold (315 s, range = 280-375 s), forearm oxygenation decreased to 29% ± 10%; and in preparation for rowing, right thigh oxygenation decreased from 66% ± 7% to 33% ± 14% (P < 0.05). Ischemic preconditioning prolonged the breath hold from 279 ± 72 to 327 ± 39 s, and the underwater swimming distance from 110 ± 16 to 119 ± 14 m (P < 0.05) and also the rowing time was reduced (from 186.5 ± 3.6 to 185.7 ± 3.6 s; P < 0.05). We conclude that while the effect of ischemic preconditioning (of one forearm) on ergometer rowing was minimal, probably because of reduced muscle oxygenation during the warm-up, ischemic preconditioning does enhance both static and dynamic apnea, supporting that muscle ischemia is an important preparation for physical activity.

  15. Window Of Opportunity: Estrogen As A Treatment For Ischemic Stroke✰

    PubMed Central

    Liu, Ran; Yang, Shao-Hua

    2013-01-01

    The neuroprotection research in the last 2 decades has witnessed a growing interest in the functions of estrogens as neuroprotectants against neurodegenerative diseases including stroke. The neuroprotective action of estrogens has been well demonstrated in both in vitro and in vivo models of ischemic stroke. However, the major conducted clinical trials so far have raised concern for the protective effect of estrogen replacement therapy in postmenopausal women. The discrepancy could be partly due to the mistranslation between the experimental stroke research and clinical trials. While predominant experimental studies tested the protective action of estrogens on ischemic stroke using acute treatment paradigm, the clinical trials have mainly focused on the effect of estrogen replacement therapy on the primary and secondary stroke prevention which has not been adequately addressed in the experimental stroke study. Although the major conducted clinical trials have indicated that estrogen replacement therapy has an adverse effect and raise concern for long term estrogen replacement therapy for stroke prevention, these are not appropriate for assessing the potential effects of acute estrogen treatment on stroke protection. The well established action of estrogen in the neurovascular unit and its potential interaction with recombinant tissue plasminogen activator (rtPA) makes it a candidate for the combined therapy with rtPA for the acute treatment of ischemic stroke. On the other hand, the “critical period” and newly emerged “biomarkers window” hypotheses have indicated that many clinical relevant factors have been underestimated in the experimental ischemic stroke research. The development and application of ischemic stroke models that replicate the clinical condition is essential for further evaluation of acute estrogen treatment on ischemic stroke which might provide critical information for future clinical trials. PMID:23340160

  16. Suppression of Acid Sphingomyelinase Protects the Retina from Ischemic Injury

    PubMed Central

    Fan, Jie; Wu, Bill X.; Crosson, Craig E.

    2016-01-01

    Purpose Acid sphingomyelinase (ASMase) catalyzes the hydrolysis of sphingomyelin to ceramide and mediates multiple responses involved in inflammatory and apoptotic signaling. However, the role ASMase plays in ischemic retinal injury has not been investigated. The purpose of this study was to investigate how reduced ASMase expression impacts retinal ischemic injury. Methods Changes in ceramide levels and ASMase activity were determined by high performance liquid chromatography-tandem mass spectrometry analysis and ASMase activity. Retinal function and morphology were assessed by electroretinography (ERG) and morphometric analyses. Levels of TNF-α were determined by ELISA. Activation of p38 MAP kinase was assessed by Western blot analysis. Results In wild-type mice, ischemia produced a significant increase in retinal ASMase activity and ceramide levels. These increases were associated with functional deficits as measured by ERG analysis and significant structural degeneration in most retinal layers. In ASMase+/− mice, retinal ischemia did not significantly alter ASMase activity, and the rise in ceramide levels were significantly reduced compared to levels in retinas from wild-type mice. In ASMase+/− mice, functional and morphometric analyses of ischemic eyes revealed significantly less retinal degeneration than in injured retinas from wild-type mice. The ischemia-induced increase in retinal TNF-α levels was suppressed by the administration of the ASMase inhibitor desipramine, or by reducing ASMase expression. Conclusions Our results demonstrate that reducing ASMase expression provides partial protection from ischemic injury. Hence, the production of ceramide and subsequent mediators plays a role in the development of ischemic retinal injury. Modulating ASMase may present new opportunities for adjunctive therapies when treating retinal ischemic disorders. PMID:27571014

  17. Genome wide analysis of blood pressure variability and ischemic stroke

    PubMed Central

    Khan, Muhammad S; Nalls, Michael A; Bevan, Steve; Cheng, Yu-Ching; Chen, Wei-Min; Malik, Rainer; McCarthy, Nina S; Holliday, Elizabeth G; Speed, Douglas; Hasan, Nazeeha; Pucek, Mateusz; Rinne, Paul E.; Sever, Peter; Stanton, Alice; Shields, Denis C; Maguire, Jane M; McEvoy, Mark; Scott, Rodney J; Ferrucci, Luigi; Macleod, Mary J; Attia, John; Markus, Hugh S; Sale, Michele M; Worrall, Bradford B; Mitchell, Braxton D; Dichgans, Martin; Sudlow, Cathy; Meschia, James F; Rothwell, Peter M

    2013-01-01

    Background and Purpose Visit-to-visit variability in BP is associated with ischemic stroke. We sought to determine whether such variability has a genetic aetiology and whether genetic variants associated with BP variability are also associated with ischemic stroke. Methods A GWAS for loci influencing BP variability was undertaken in 3,802 individuals from the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) study where long-term visit-to-visit and within visit BP measures were available. Since BP variability is strongly associated with ischemic stroke, we genotyped the sentinel SNP in an independent ischemic stroke population comprising of 8,624 cases and 12,722 controls and in 3,900 additional (Scandinavian) participants from the ASCOT study in order to replicate our findings. Results The ASCOT discovery GWAS identified a cluster of 17 correlated SNPs within the NLGN1 gene (3q26.31) associated with BP variability. The strongest association was with rs976683 (p=1.4×10−8). Conditional analysis on rs976683 provided no evidence of additional independent associations at the locus. Analysis of rs976683 in ischemic stroke patients found no association for overall stroke (OR 1.02; 95% CI 0.97-1.07; p=0.52) or its sub-types: CE (OR 1.07; 95% CI 0.97-1.16; p=0.17), LVD (OR 0.98; 95% 0.89-1.07; p=0.60) and SVD (OR 1.07; 95% CI 0.97-1.17; p=0.19). No evidence for association was found between rs976683 and BP variability in the additional (Scandinavian) ASCOT participants (p=0.18). Conclusions We identified a cluster of SNPs at the NLGN1 locus showing significant association with BP variability. Follow up analyses did not support an association with risk of ischemic stroke and its subtypes. PMID:23929743

  18. Caffeine prevents protection in two human models of ischemic preconditioning.

    PubMed

    Riksen, Niels P; Zhou, Zhigang; Oyen, Wim J G; Jaspers, Rogier; Ramakers, Bart P; Brouwer, Rene M H J; Boerman, Otto C; Steinmetz, Neil; Smits, Paul; Rongen, Gerard A

    2006-08-15

    We studied whether caffeine impairs protection by ischemic preconditioning (IP) in humans. Ischemic preconditioning is critically dependent on adenosine receptor stimulation. We hypothesize that the adenosine receptor antagonist caffeine blocks the protective effect of IP. In vivo ischemia-reperfusion injury was assessed in the thenar muscle by 99mTc-annexin A5 scintigraphy. Forty-two healthy volunteers performed forearm ischemic exercise. In 24 subjects, this was preceded by a stimulus for IP. In a randomized double-blinded design, the subjects received caffeine (4 mg/kg) or saline intravenously before the experiment. At reperfusion, 99mTc-annexin A5 was administered intravenously. Targeting of annexin was quantified by region-of-interest analysis, and expressed as percentage difference between experimental and contralateral hand. In vitro, we assessed recovery of contractile function of human atrial trabeculae, harvested during heart surgery, as functional end point of ischemia-reperfusion injury. Field-stimulated contraction was quantified at baseline and after simulated ischemia-reperfusion, in a paired approach with and without 5 min of IP, in the presence (n=13) or absence (n = 17) of caffeine (10 mg/l). Ischemic preconditioning reduced annexin targeting in the absence of caffeine (from 13 +/- 3% to 7 +/- 1% at 1 h, and from 19 +/- 2% to 9 +/- 3% at 4 h after reperfusion, p = 0.006), but not after caffeine administration (targeting 11 +/- 2% and 16 +/- 3% at 1 and 4 h). In vitro, IP improved post-ischemic functional recovery in the control group, but not in the caffeine group (8 +/- 3% vs. -8 +/- 5%, p=0.003). Caffeine abolishes IP in 2 human models at a dose equivalent to the drinking of 2 to 4 cups of coffee. (The Effect of Caffeine on Ischemic Preconditioning; http://clinicaltrials.gov/ct/show/NCT00184912?order=1; NCT00184912).

  19. Apoptosis and Acute Brain Ischemia in Ischemic Stroke.

    PubMed

    Radak, Djordje; Katsiki, Niki; Resanovic, Ivana; Jovanovic, Aleksandra; Sudar-Milovanovic, Emina; Zafirovic, Sonja; Mousad, Shaker A; Isenovic, Esma R

    2017-01-01

    Apoptosis may contribute to a significant proportion of neuron death following acute brain ischemia (ABI), but the underlying mechanisms are still not fully understood. Brain ischemia may lead to stroke, which is one of the main causes of long-term morbidity and mortality in both developed and developing countries. Therefore, stroke prevention and treatment is clinically important. There are two important separate areas of the brain during ABI: the ischemic core and the ischemic penumbra. The ischemic core of the brain experiences a sudden reduction of blood flow, just minutes after ischemic attack with irreversible injury and subsequent cell death. On the other hand, apoptosis within the ischemic penumbra may occur after several hours or days, while necrosis starts in the first hours after the onset of ABI in the ischemic core. ABI is characterized by key molecular events that initiate apoptosis in many cells, such as overproduction of free radicals, Ca2+ overload and excitotoxicity. These changes in cellular homeostasis may trigger either necrosis or apoptosis, which often depends on cell type, cell age, and location in the brain. Apoptosis results in DNA fragmentation, degradation of cytoskeletal and nuclear proteins, cross-linking of proteins, formation of apoptotic bodies, expression of ligands for phagocytic cell receptors and finally uptake by phagocytic cells. This review focuses on recent findings based on animal and human studies regarding the apoptotic mechanisms of neuronal death following ABI and the development of potential neuroprotective agents that reduce morbidity. The effects of statins on stroke prevention and treatment as well as on apoptotic mediators are also considered. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. In vivo characterization of ischemic retina in diabetic retinopathy

    PubMed Central

    Reznicek, Lukas; Kernt, Marcus; Haritoglou, Christos; Kampik, Anselm; Ulbig, Michael; Neubauer, Aljoscha S

    2011-01-01

    Objective The aim of this article is to characterize pathomorphologic changes within particular layers of fluorescein angiographically ‘ischemic’ compared to ‘nonischemic’ retina in patients with diabetic retinopathy. Methods Cross-sectional images of ischemic retinal areas were obtained using Heidelberg Spectralis optical coherence tomography (OCT). Presumed retinal ischemia was defined as focal hypofluorescence in early or early and late phase fluorescein angiography. Pathomorphologic changes on OCT were evaluated and the thickness of retinal layers measured and compared with nonischemic retina at corresponding topographic locations in a matched-pairs design based on 22 eyes (mean age 64 ± 14). Results In all eyes, based on spectral domain-OCT cross-section images, the retina layers in ischemic retinal areas could be segmented. Total retinal thickness was significantly increased in ischemic compared to nonischemic areas (381 ± 94 μm versus 323 ± 89 μm, P = 0.005). Middle retinal layers (inner nuclear layer, outer plexiform layer, and outer nuclear layer) were significantly thickened in retinal ischemic areas (215 ± 82 μm versus 168 ± 62 μm, P = 0.002). The inner retinal layers (retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer) showed a nonsignificant change (117 ± 53 μm versus 98 ± 30 μm), while the outer layers were slightly thinned (photoreceptors plus retinal pigment epithelium layer; 51 ± 9 μm versus 57 ± 8 μm, P = 0.02) in ischemic versus nonischemic retina. Conclusions Ischemic diabetic retina seems to be thickened due to thickening of, in particular, middle retinal layers, which can be measured with high-resolution OCT. PMID:21311655

  1. A multicenter, randomized trial on neuroprotection with remote ischemic per-conditioning during acute ischemic stroke: the REmote iSchemic Conditioning in acUtE BRAin INfarction study protocol.

    PubMed

    Pico, Fernando; Rosso, Charlotte; Meseguer, Elena; Chadenat, Marie-Laure; Cattenoy, Amina; Aegerter, Philippe; Deltour, Sandrine; Yeung, Jennifer; Hosseini, Hassan; Lambert, Yves; Smadja, Didier; Samson, Yves; Amarenco, Pierre

    2016-10-01

    Rationale Remote ischemic per-conditioning-causing transient limb ischemia to induce ischemic tolerance in other organs-reduces final infarct size in animal stroke models. Aim To evaluate whether remote ischemic per-conditioning during acute ischemic stroke (<6 h) reduces brain infarct size at 24 h. Methods and design This study is being performed in five French hospitals using a prospective randomized open blinded end-point design. Adults with magnetic resonance imaging confirmed ischemic stroke within 6 h of symptom onset and clinical deficit of 5-25 according to National Institutes of Health Stroke Scale will be randomized 1:1 to remote ischemic per-conditioning or control (stratified by center and intravenous fibrinolysis use). Remote ischemic per-conditioning will consist of four cycles of electronic tourniquet inflation (5 min) and deflation (5 min) to a thigh within 6 h of symptom onset. Magnetic resonance imaging is repeated 24 h after stroke onset. Sample size estimates For a difference of 15 cm(3) in brain infarct growth between groups, 200 patients will be included for 5% significance and 80% power. Study outcomes The primary outcome will be the difference in brain infarct growth from baseline to 24 h in the intervention versus control groups (by diffusion-weighted image magnetic resonance imaging). Secondary outcomes include: National Institutes of Health Stroke Scale score absolute difference between baseline and 24 h, three-month modified Rankin score and daily living activities, mortality, and tolerance and side effects of remote ischemic per-conditioning. Discussion The only remote ischemic per-conditioning trial in humans with stroke did not show remote ischemic per-conditioning to be effective. REmote iSchemic Conditioning in acUtE BRAin INfarction, which has important design differences, should provide more information on the use of this intervention in patients with acute ischemic stroke.

  2. Phosphoproteomic Profiling of Human Myocardial Tissues Distinguishes Ischemic from Non-Ischemic End Stage Heart Failure

    PubMed Central

    Njoroge, Linda W.; Thompson, J. Will; Soderblom, Erik J.; Feger, Bryan J.; Troupes, Constantine D.; Hershberger, Kathleen A.; Ilkayeva, Olga R.; Nagel, Whitney L.; Landinez, Gina P.; Shah, Kishan M.; Burns, Virginia A.; Santacruz, Lucia; Hirschey, Matthew D.; Foster, Matthew W.; Milano, Carmelo A.; Moseley, M. Arthur; Piacentino, Valentino; Bowles, Dawn E.

    2014-01-01

    The molecular differences between ischemic (IF) and non-ischemic (NIF) heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins) and 823 phosphopeptides (corresponding to 400 proteins) from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins) exhibited a ≥2-fold alteration in phosphorylation state (p<0.05) when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure. PMID:25117565

  3. Smartphone electrographic monitoring for atrial fibrillation in acute ischemic stroke and transient ischemic attack.

    PubMed

    Tu, Hans T; Chen, Ziyuan; Swift, Corey; Churilov, Leonid; Guo, Ruibing; Liu, Xinfeng; Jannes, Jim; Mok, Vincent; Freedman, Ben; Davis, Stephen M; Yan, Bernard

    2017-10-01

    Rationale Paroxysmal atrial fibrillation is a common and preventable cause of devastating strokes. However, currently available monitoring methods, including Holter monitoring, cardiac telemetry and event loop recorders, have drawbacks that restrict their application in the general stroke population. AliveCor™ heart monitor, a novel device that embeds miniaturized electrocardiography (ECG) in a smartphone case coupled with an application to record and diagnose the ECG, has recently been shown to provide an accurate and sensitive single lead ECG diagnosis of atrial fibrillation. This device could be used by nurses to record a 30-s ECG instead of manual pulse taking and automatically provide a diagnosis of atrial fibrillation. Aims To compare the proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring with current standard practice. Sample size 296 Patients. Design Consecutive ischemic stroke and transient ischemic attack patients presenting to participating stroke units without known atrial fibrillation will undergo intermittent AliveCor™ ECG monitoring administered by nursing staff at the same frequency as the vital observations of pulse and blood pressure until discharge, in addition to the standard testing paradigm of each participating stroke unit to detect paroxysmal atrial fibrillation. Study outcome Proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring compared to 12-lead ECG, 24-h Holter monitoring and cardiac telemetry. Discussion Use of AliveCor™ heart monitor as part of routine stroke unit nursing observation has the potential to be an inexpensive non-invasive method to increase paroxysmal atrial fibrillation detection, leading to improvement in stroke secondary prevention.

  4. Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.

    PubMed

    Schechter, Matthew A; Hsieh, Michael K H; Njoroge, Linda W; Thompson, J Will; Soderblom, Erik J; Feger, Bryan J; Troupes, Constantine D; Hershberger, Kathleen A; Ilkayeva, Olga R; Nagel, Whitney L; Landinez, Gina P; Shah, Kishan M; Burns, Virginia A; Santacruz, Lucia; Hirschey, Matthew D; Foster, Matthew W; Milano, Carmelo A; Moseley, M Arthur; Piacentino, Valentino; Bowles, Dawn E

    2014-01-01

    The molecular differences between ischemic (IF) and non-ischemic (NIF) heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins) and 823 phosphopeptides (corresponding to 400 proteins) from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins) exhibited a ≥ 2-fold alteration in phosphorylation state (p<0.05) when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure.

  5. A practical approach to remote ischemic preconditioning and ischemic preconditioning against myocardial ischemia/reperfusion injury

    PubMed Central

    Totzeck, Matthias; Hendgen-Cotta, Ulrike B.; French, Brent A.; Rassaf, Tienush

    2016-01-01

    Although urgently needed in clinical practice, a cardioprotective therapeutic approach against myocardial ischemia/ reperfusion injury remains to be established. Remote ischemic preconditioning (rIPC) and ischemic preconditioning (IPC) represent promising tools comprising three entities: the generation of a protective signal, the transfer of the signal to the target organ, and the response to the transferred signal resulting in cardioprotection. However, in light of recent scientific advances, many controversies arise regarding the efficacy of the underlying signaling. We here show methods for the generation of the signaling cascade by rIPC as well as IPC in a mouse model for in vivo myocardial ischemia/ reperfusion injury using highly reproducible approaches. This is accomplished by taking advantage of easily applicable preconditioning strategies compatible with the clinical setting. We describe methods for using laser Doppler perfusion imaging to monitor the cessation and recovery of perfusion in real time. The effects of preconditioning on cardiac function can also be assessed using ultrasound or magnetic resonance imaging approaches. On a cellular level, we confirm how tissue injury can be monitored using histological assessment of infarct size in conjunction with immunohistochemistry to assess both aspects in a single specimen. Finally, we outline, how the rIPC-associated signaling can be transferred to the target cell via conservation of the signal in the humoral (blood) compartment. This compilation of experimental protocols including a conditioning regimen comparable to the clinical setting should proof useful to both beginners and experts in the field of myocardial infarction, supplying information for the detailed procedures as well as troubleshooting guides. PMID:28066791

  6. Intrapulmonary shunt is a potentially unrecognized cause of ischemic stroke and transient ischemic attack.

    PubMed

    Abushora, Mohannad Y; Bhatia, Nirmanmoh; Alnabki, Ziad; Shenoy, Mohan; Alshaher, Motaz; Stoddard, Marcus F

    2013-07-01

    Ischemic stroke is a major cause of mortality and disability. Transient ischemic attack (TIA) is a harbinger of stroke. The etiology of stroke in as many as 40% of patients remains undetermined after extensive evaluation. It was hypothesized that intrapulmonary shunt is a potential facilitator of cerebrovascular accident (CVA) or TIA. Patients undergoing clinically indicated transesophageal echocardiography were prospectively enrolled. Comprehensive multiplane transesophageal echocardiographic imaging was performed and saline contrast done to assess for intrapulmonary shunt and patent foramen ovale. Three hundred twenty-one patients with either nonhemorrhagic CVA (n = 262) or TIA (n = 59) made up the stroke group. Three hundred twenty-one age-matched and gender-matched patients made up the control group. Intrapulmonary shunt occurred more frequently in the stroke group (72 of 321) compared with the control group (32 of 321) (22% vs 10%, P < .0001). Intrapulmonary shunt was an independent predictor of CVA and/or TIA (odds ratio, 2.6; P < .0001). In subjects with cryptogenic CVA or TIA (n = 71), intrapulmonary shunt occurred more frequently (25 of 71) than in the control group (5 of 71) (35% vs 7%, P < .0001). Intrapulmonary shunt was an independent multivariate predictor of CVA or TIA in patients with cryptogenic CVA or TIA (odds ratio, 6.3; P < .005). These results suggest that intrapulmonary shunt is a potentially unrecognized facilitator of CVA and TIA, especially in patients with cryptogenic CVA and TIA. Future studies assessing the prognostic significance of intrapulmonary shunt on cerebral vascular event recurrence rates in patients after initial CVA or TIA would be of great interest. Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

  7. Ischemic preconditioning protects against gap junctional uncoupling in cardiac myofibroblasts.

    PubMed

    Sundset, Rune; Cooper, Marie; Mikalsen, Svein-Ole; Ytrehus, Kirsti

    2004-01-01

    Ischemic preconditioning increases the heart's tolerance to a subsequent longer ischemic period. The purpose of this study was to investigate the role of gap junction communication in simulated preconditioning in cultured neonatal rat cardiac myofibroblasts. Gap junctional intercellular communication was assessed by Lucifer yellow dye transfer. Preconditioning preserved intercellular coupling after prolonged ischemia. An initial reduction in coupling in response to the preconditioning stimulus was also observed. This may protect neighboring cells from damaging substances produced during subsequent regional ischemia in vivo, and may preserve gap junctional communication required for enhanced functional recovery during subsequent reperfusion.

  8. Factoring in Factor VIII With Acute Ischemic Stroke.

    PubMed

    Siegler, James E; Samai, Alyana; Albright, Karen C; Boehme, Amelia K; Martin-Schild, Sheryl

    2015-10-01

    There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke.

  9. A rating system for prompt clinical diagnosis of ischemic stroke.

    PubMed

    Talavera, J O; Wacher, N H; Laredo, F; López, A; Martínez, V; González, J; Lifshitz, A; Feinstein, A R

    2000-01-01

    When a CT scan is not available, an early accurate clinical diagnosis of ischemic stroke is essential to initiate prompt therapy. Our objective was to construct a clinical index that is easy to use when stroke patients are first evaluated at the hospital, to identify those who probably are experiencing an acute ischemic episode. The study was conducted at a university-affiliated medical referral center and two community general hospitals in Mexico. Clinical records were reviewed for 801 patients with sudden onset of a focal or global neurologic dysfunction, presumably of vascular origin lasting more than 24 h. Eligibility criteria for this study were admission to the hospital within the first 24 h after symptomatic onset, CT scan diagnosis between 24 and 72 h, and age >45 years. Ischemic stroke included cases of arterial brain infarction, while nonischemic stroke included subarachnoid or intraparenchymatous hemorrhage, mass lesion, venous infarction, and in cases without a CT scan evidence that could explain the clinical manifestations. Data excerpted for analysis were age, sex, history of diabetes mellitus or previous stroke/transient ischemic attack (TIA), time of onset of symptoms, presence of headache, vomiting, neck stiffness, hemiplegia, leukocytosis or atrial fibrillation, diastolic blood pressure, and Glasgow coma scale (GCS) rating. Two multivariable analyses were used: 1) step-wise multiple logistic regression (SMLR), and 2) conjunctive consolidation (CC). After appropriate exclusions, the study proceeded with 83 ischemic and 42 nonischemic stroke patients. With SMLR, six variables were selected as predictive for ischemic stroke, including neck stiffness, diastolic blood pressure, previous history of stroke/TIA, hemiplegia, GCS, and atrial fibrillation. An appropriate sum of weighted ratings had a positive predictive value (PPV) of 100% for ischemic stroke. With consolidated categories, the PPV was 97% when patients had the following: no neck stiffness

  10. Neuroprotection in the Treatment of Acute Ischemic Stroke.

    PubMed

    Patel, Rajan A G; McMullen, Paul W

    Neuroprotection remains one of the holy grails of acute ischemic stroke therapy. The ability to protect the ischemic brain from injury until reperfusion and then to protect the brain from reperfusion injury could theoretically improve freedom from disability among stroke survivors. This manuscript reviews the molecular and cellular pathophysiology of stroke and summarizes pharmacologic and other therapies that showed promise in pre-clinical testing as neuroprotection agents. However to date, no compelling efficacy data have been published regarding any pharmacologic or other therapies. Nonetheless the search for effective neuroprotection continues at stroke centers throughout the world. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. NOTCH3 Variants and Risk of Ischemic Stroke

    PubMed Central

    Ross, Owen A.; Soto-Ortolaza, Alexandra I.; Heckman, Michael G.; Verbeeck, Christophe; Serie, Daniel J.; Rayaprolu, Sruti; Rich, Stephen S.; Nalls, Michael A.; Singleton, Andrew; Guerreiro, Rita; Kinsella, Emma; Wszolek, Zbigniew K.; Brott, Thomas G.; Brown, Robert D.; Worrall, Bradford B.; Meschia, James F.

    2013-01-01

    Background Mutations within the NOTCH3 gene cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). CADASIL mutations appear to be restricted to the first twenty-four exons, resulting in the gain or loss of a cysteine amino acid. The role of other exonic NOTCH3 variation not involving cysteine residues and mutations in exons 25-33 in ischemic stroke remains unresolved. Methods All 33 exons of NOTCH3 were sequenced in 269 Caucasian probands from the Siblings With Ischemic Stroke Study (SWISS), a 70-center North American affected sibling pair study and 95 healthy Caucasian control subjects. Variants identified by sequencing in the SWISS probands were then tested for association with ischemic stroke using US Caucasian controls collected at the Mayo Clinic (n=654), and further assessed in a Caucasian (n=802) and African American (n=298) patient-control series collected through the Ischemic Stroke Genetics Study (ISGS). Results Sequencing of the 269 SWISS probands identified one (0.4%) with small vessel type stroke carrying a known CADASIL mutation (p.R558C; Exon 11). Of the 19 common NOTCH3 variants identified, the only variant significantly associated with ischemic stroke after multiple testing adjustment was p.R1560P (rs78501403; Exon 25) in the combined SWISS and ISGS Caucasian series (Odds Ratio [OR] 0.50, P=0.0022) where presence of the minor allele was protective against ischemic stroke. Although only significant prior to adjustment for multiple testing, p.T101T (rs3815188; Exon 3) was associated with an increased risk of small-vessel stroke (OR: 1.56, P=0.008) and p.P380P (rs61749020; Exon 7) was associated with decreased risk of large-vessel stroke (OR: 0.35, P=0.047) in Caucasians. No significant associations were observed in the small African American series. Conclusion Cysteine-affecting NOTCH3 mutations are rare in patients with typical ischemic stroke, however our observation that common NOTCH3 variants

  12. Parinaud's syndrome due to an unilateral vascular ischemic lesion.

    PubMed

    Serino, Josefina; Martins, João; Páris, Liliana; Duarte, Ana; Ribeiro, Isabel

    2015-04-01

    A 59-year-old man who complained of binocular vertical diplopia after an exploratory laparotomy, complicated by cardiorespiratory arrest during anesthetic induction, was found to have Collier's sign, anisocoria, complete paralysis of upward vertical gaze associated with convergence-retraction nystagmus on attempted upgaze and skew deviation with hypertropia in the left eye without ptosis, and an absent Bielschowsky sign. Magnetic resonance imaging of the brain showed a small lesion in the left paramedian midbrain compatible with microvascular ischemic sequelae. This patient was diagnosed with Parinaud's syndrome (dorsal midbrain syndrome) associated with a vertical strabismus from an unilateral vascular ischemic paramedian midbrain lesion.

  13. Anesthesia for Endovascular Approaches to Acute Ischemic Stroke.

    PubMed

    Avitsian, Rafi; Machado, Sandra B

    2016-09-01

    Involvement of the Anesthesiologist in the early stages of care for acute ischemic stroke patient undergoing endovascular treatment is essential. Anesthetic management includes the anesthetic technique (general anesthesia vs sedation), a matter of much debate and an area in need of well-designed prospective studies. The large numbers of confounding factors make the design of such studies a difficult process. A universally agreed point in the endovascular management of acute ischemic stroke is the importance of decreasing the time to revascularization. Hemodynamic and ventilatory management and implementation of neuroprotective modalities and treatment of acute procedural complications are important components of the anesthetic plan. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Intravenous tenecteplase in acute ischemic stroke: an updated review.

    PubMed

    Behrouz, Réza

    2014-06-01

    Tenecteplase in a genetically engineered variant of alteplase. Although the two have the same mechanism of action, tenecteplase has properties that makes it a seemingly more advantageous thrombolytic. Because of its rapid single-bolus administration, its use is favored over alteplase in the treatment of acute myocardial infarction. Over the past few years, several clinical studies have been conducted to assess the safety, feasibility, and efficacy of tenecteplase in ischemic stroke. In spite of the mixed results of these studies, experimentation with tenecteplase continues in from of clinical trials. In this article, the utility of tenecteplase in ischemic stroke will be discussed.

  15. Factors predicting poor prognosis in ischemic colitis

    PubMed Central

    Añón, Ramón; Boscá, Marta Maia; Sanchiz, Vicente; Tosca, Joan; Almela, Pedro; Amorós, Cirilo; Benages, Adolfo

    2006-01-01

    AIM: To determine the clinical, analytical and endoscopic factors related to ischemic colitis (IC) severity. METHODS: A total of 85 patients were enrolled in a retrospective study from January 1996 to May 2004. There were 53 females and 32 males (age 74.6 ± 9.4 years, range 45-89 years). The patients were diagnosed as IC. The following variables were analyzed including age, sex, period of time from the appearance of symptoms to admission, medical history, medication, stool frequency, clinical symptoms and signs, blood tests (hemogram and basic biochemical profile), and endoscopic findings. Patients were divided in mild IC group and severe IC group (surgery and/or death). Qualitative variables were analyzed using chi-square test and parametric data were analyzed using Student's t test (P < 0.05). RESULTS: The mild IC group was consisted of 69 patients (42 females and 27 males, average age 74.7 ± 12.4 years). The severe IC group was composed of 16 patients (11 females and 5 males, average age of 73.8 ± 12.4 years). One patient died because of failure of medical treatment (no surgery), 15 patients underwent surgery (6 after endoscopic diagnosis and 9 after peroperatory diagnosis). Eight of 85 patients (9.6%) died and the others were followed up as out-patients for 9.6 ± 3.5 mo. Demographic data, medical history, medication and stool frequency were similar in both groups (P > 0.05). Seriously ill patients had less hematochezia than slightly ill patients (37.5% vs 86.9%, P = 0.000). More tachycardia (45.4% vs 10.1%, P = 0.011) and a higher prevalence of peritonism signs (75% vs 5.7%, P = 0.000) were observed in the severe IC group while the presence and intensity of abdominal pain were similar between two groups. Two patients with severe IC had shock when admitted. Regarding analytical data, more seriously ill patients were found to have anemia and hyponatremia than the mildly ill patients (37.5% vs 10.1%, P = 0.014 and 46.6% vs 14.9%, P = 0.012, respectively

  16. HIF-1α, MDM2, CDK4, and p16 expression in ischemic fasciitis, focusing on its ischemic condition.

    PubMed

    Yamada, Yuichi; Kinoshita, Izumi; Kohashi, Kenichi; Yamamoto, Hidetaka; Kuma, Yuki; Ito, Takamichi; Koda, Kenji; Kisanuki, Atsushi; Kurosawa, Manabu; Yoshimura, Michiko; Furue, Masutaka; Oda, Yoshinao

    2017-07-01

    Ischemic fasciitis is a benign myofibroblastic lesion, occurring in the sacral region or proximal thigh of elderly or bedridden individuals. The pathogenesis of ischemic fasciitis is thought to be based on ischemic condition; however, it has never been demonstrated. In this study, we examined the expression of ischemia-associated proteins in ischemic fasciitis by immunohistochemical and genetic methods. Specifically, this study aimed to reveal the expression of HIF-1α, MDM2, CDK4, p16, and gene amplification of MDM2 gene. Seven cases of ischemic fasciitis from among the soft-tissue tumors registered at our institution were retrieved. Histopathological findings were as follows: poorly demarcated nodular masses, a proliferation of spindle-shaped fibroblastic or myofibroblastic cells with oval nuclei and eosinophilic or pale cytoplasm, zonal fibrinous deposition, pseudocystic degeneration, granulation-like proliferation of capillary vessels, ganglion-like cells, myxoid or hyalinized stroma, and chronic inflammatory infiltration. Immunohistochemically, the spindle cells were positive for HIF-1α (7/7 cases), MDM2 (4/7 cases), CDK4 (4/7 cases), p16 (7/7 cases), p53 (2/7 case), cyclin D1 (7/7 cases), and alpha-smooth muscle actin (6/7 cases). Neither MDM2 gene amplification nor USP6 gene split signal was detected in any case. Overexpression of the above proteins may be associated with the pathogenic mechanism of ischemic fasciitis. It is noted that the immunohistochemical positivity of MDM2, CDK4, and p16 do not necessarily indicate malignant neoplasm such as dedifferentiated liposarcoma.

  17. Characterization of pericardial and plasma ghrelin levels in patients with ischemic and non-ischemic heart disease.

    PubMed

    Sax, Balazs; Merkely, Béla; Túri, Katalin; Nagy, Andrea; Ahres, Abdelkrim; Hartyánszky, István; Hüttl, Tivadar; Szabolcs, Zoltán; Cseh, Károly; Kékesi, Violetta

    2013-09-10

    Ghrelin is an endocrine regulatory peptide with multiple functions including cardioprotective effects. It is produced in various tissues among others in the myocardium. Pericardial fluid has been proven to be a biologically active compartment of the heart that communicates with the myocardial interstitium. Thus, pericardial level of certain agents may reflect their concentration in the myocardium well. In our study we measured acylated (active) and total (acylated and non-acylated) pericardial and plasma ghrelin levels of patients with ischemic and non-ischemic heart disease. Pericardial fluid and plasma samples were obtained from patients with coronary artery disease (ISCH, n=54) or valvular heart disease (VHD, n=41) undergoing cardiac surgery. Acylated pericardial ghrelin concentrations were found to be significantly higher in patients with ischemic heart disease (ISCH vs. VHD, 32±3 vs. 16±2pg/ml, p<0.01), whereas plasma levels of the peptide showed no difference between patient groups. Pericardial-to-plasma ratio, an index abolishing systemic effects on local ghrelin level was also significantly higher in ISCH group for both acylated and total ghrelin. Plasma total ghrelin showed negative correlation to BMI, plasma insulin and insulin resistance index HOMA-A. Pericardial acylated and total ghrelin concentrations were negatively correlated with posterior wall thickness (R=-0.31, p<0.05 and R=-0.35, p<0.01, respectively). Plasma insulin concentration and HOMA-A showed significant negative correlation with pericardial ghrelin levels. In conclusion, increased pericardial active ghrelin content and higher pericardial-to-plasma ghrelin ratio were found in ischemic heart disease as compared to non-ischemic patients suggesting an increased ghrelin production of the chronically ischemic myocardium. According to our results, pericardial ghrelin content is negatively influenced by left ventricular hypertrophy and insulin resistance.

  18. Medications Used in the Treatment of Ischemic Heart Disease.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on medications used in the treatment of ischemic heart disease is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first.…

  19. Remote limb ischemic conditioning enhances motor learning in healthy humans

    PubMed Central

    Cherry-Allen, Kendra M.; Gidday, Jeff M.; Lee, Jin-Moo; Hershey, Tamara

    2015-01-01

    Brief bouts of sublethal ischemia have been shown to protect exposed tissue (ischemic conditioning) and tissues at remote sites (remote ischemic conditioning) against subsequent ischemic challenges. Given that the mechanisms of this protective phenomenon are multifactorial and epigenetic, we postulated that remote limb ischemic conditioning (RLIC) might enhance mechanisms responsible for neural plasticity, and thereby facilitate learning. Specifically, we hypothesized that conditioning of the nervous system with RLIC, achieved through brief repetitive limb ischemia prior to training, would facilitate the neurophysiological processes of learning, thus making training more effective and more long-lasting. Eighteen healthy adults participated in this study; nine were randomly allocated to RLIC and nine to sham conditioning. All subjects underwent seven consecutive weekday sessions and 2-wk and 4-wk follow-up sessions. We found that RLIC resulted in significantly greater motor learning and longer retention of motor performance gains in healthy adults. Changes in motor performance do not appear to be due to a generalized increase in muscle activation or muscle strength and were not associated with changes in serum brain-derived neurotrophic factor (BDNF) concentration. Of note, RLIC did not enhance cognitive learning on a hippocampus-dependent task. While future research is needed to establish optimal conditioning and training parameters, this inexpensive, clinically feasible paradigm might ultimately be implemented to enhance motor learning in individuals undergoing neuromuscular rehabilitation for brain injury and other pathological conditions. PMID:25867743

  20. Non-Ischemic Cardiomyopathy Attributed to Adult Myotonic Dystrophy

    PubMed Central

    Park, Hyun Kyung; Park, Won Hyeong; Song, Dae-Geun; Kim, Tae Gyoon; Min, Bo Young; Lee, Keun

    2009-01-01

    In patients with myotonic dystrophy (MD), impairment of the conduction system is a common and progressive finding. However, only a few cases of MD with cardiomyopathy have been reported. Herein we report a case of MD with progressive non-ischemic cardiomyopathy and severe electrocardiographic abnormalities. PMID:19949641

  1. Reactive astrocytes and therapeutic potential in focal ischemic stroke

    PubMed Central

    Choudhury, Gourav Roy; Ding, Shinghua

    2015-01-01

    Astrocytes are specialized and the most abundant cell type in the central nervous system (CNS). They play important roles in the physiology of the brain. Astrocytes are also critically involved in many CNS disorders including focal ischemic stroke, the leading cause of brain injury and death in patients. One of the prominent pathological features of a focal ischemic stroke is reactive astrogliosis and glial scar formation. Reactive astrogliosis is accompanied with changes in morphology, proliferation and gene expression in the reactive astrocytes. This study provides an overview of the most recent advances in astrocytic Ca2+ signaling, spatial and temporal dynamics of the morphology and proliferation of reactive astrocytes as well as signaling pathways involved in the reactive astrogliosis after ischemic stroke based on results from experimental studies performed in various animal models. This review also discusses the therapeutic potential of reactive astrocytes in a focal ischemic stroke. As reactive astrocytes exhibit high plasticity, we suggest that modulation of local reactive astrocytes is a promising strategy for cell-based stroke therapy. PMID:25982835

  2. [Bilateral ischemic optic neuropathy secondary to acute ergotism].

    PubMed

    Sommer, S; Delemazure, B; Wagner, M; Xenard, L; Rozot, P

    1998-02-01

    We report a case of a 31 year-old man who presented a bilateral ischemic optic neuropathy associated with headaches and severe systemic hypertension. This episode appeared after administration of ergotamine tartrate and macrolides. This medication probably led to a vasospasm which occurs in patients with hypertension. The cardiovascular and serum lipid evaluations were normal. A migraine optic neuropathy can be evoked.

  3. Heat shock proteins, end effectors of myocardium ischemic preconditioning?

    PubMed Central

    Guisasola, María Concepcion; Desco, Maria del Mar; Gonzalez, Fernanda Silvana; Asensio, Fernando; Dulin, Elena; Suarez, Antonio; Garcia Barreno, Pedro

    2006-01-01

    The purpose of this study was to investigate (1) whether ischemia-reperfusion increased the content of heat shock protein 72 (Hsp72) transcripts and (2) whether myocardial content of Hsp72 is increased by ischemic preconditioning so that they can be considered as end effectors of preconditioning. Twelve male minipigs (8 protocol, 4 sham) were used, with the following ischemic preconditioning protocol: 3 ischemia and reperfusion 5-minute alternative cycles and last reperfusion cycle of 3 hours. Initial and final transmural biopsies (both in healthy and ischemic areas) were taken in all animals. Heat shock protein 72 messenger ribonucleic acid (mRNA) expression was measured by a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method using complementary DNA normalized against the housekeeping gene cyclophilin. The identification of heat shock protein 72 was performed by immunoblot. In our “classic” preconditioning model, we found no changes in mRNA hsp72 levels or heat shock protein 72 content in the myocardium after 3 hours of reperfusion. Our experimental model is valid and the experimental techniques are appropriate, but the induction of heat shock proteins 72 as end effectors of cardioprotection in ischemic preconditioning does not occur in the first hours after ischemia, but probably at least 24 hours after it, in the so-called “second protection window.” PMID:17009598

  4. [Neuroprotective therapy for the treatment of acute ischemic stroke].

    PubMed

    Naritomi, H

    2001-12-01

    Following cerebral ischemia, various biochemical reactions are provoked in a stepwise manner leading neuronal cells to ischemic death. The prevention of these biochemical reactions may exert neuroprotective actions and consequently reduce the magnitude of ischemic cerebral injury. On the basis of such a view, numerous neuroprotective drugs have been developed during the last decade. Quite a few drugs were found effective in reducing the infarct volume in experimental studies, and more than 15 of them were subjected to clinical phase III trials to see a therapeutic effectiveness. However, the results of phase III trials were disappointing in the majority drugs. Only three drugs, nicaravene, ebselen and edaravone, all radical scavengers, were judged effective by small-sized trials with a wide therapeutic window, 48-72 hours after stroke, in Japan. The fact suggests that a one-point prevention of biochemical reactions by single drug is unable to rescue ischemic neuronal cells. Ischemic insult causes damages of vascular wall including the endothelium which play an important role in the development of hemorrhagic changes or cerebral edema. Vascular protection is considered as important as neuroprotection in treatment of clinical stroke. Mild hypothermia has neuroprotective and vascular protective actions and hence may be more effective than neuroprotective drugs for the treatment of stroke. The prevention of fever, which often occurs in severe stroke, may exert the similar effect as hypothermia in neuroprotection. Neuroprotective therapy in the future should proceed toward the simultaneous protections of neurons and vessels using combination of multiple drugs.

  5. The neuroprotective roles of BDNF in hypoxic ischemic brain injury

    PubMed Central

    CHEN, AI; XIONG, LI-JING; TONG, YU; MAO, MENG

    2013-01-01

    Hypoxia-ischemia (H/I) brain injury results in various degrees of damage to the body, and the immature brain is particularly fragile to oxygen deprivation. Hypothermia and erythropoietin (EPO) have long been known to be neuroprotective in ischemic brain injury. Brain-derived neurotrophic factor (BDNF) has recently been recognized as a potent modulator capable of regulating a wide repertoire of neuronal functions. This review was based on studies concerning the involvement of BDNF in the protection of H/I brain injury following a search in PubMed between 1995 and December, 2011. We initially examined the background of BDNF, and then focused on its neuroprotective mechanisms against ischemic brain injury, including its involvement in promoting neural regeneration/cognition/memory rehabilitation, angiogenesis within ischemic penumbra and the inhibition of the inflammatory process, neurotoxicity, epilepsy and apoptosis. We also provided a literature overview of experimental studies, discussing the safety and the potential clinical application of BDNF as a neuroprotective agent in the ischemic brain injury. PMID:24648914

  6. Ischemic Tolerance Protects the Rat Retina from Glaucomatous Damage

    PubMed Central

    Belforte, Nicolás; Sande, Pablo H.; de Zavalía, Nuria; Fernandez, Diego C.; Silberman, Dafne M.; Chianelli, Mónica S.; Rosenstein, Ruth E.

    2011-01-01

    Glaucoma is a leading cause of acquired blindness which may involve an ischemic-like insult to retinal ganglion cells and optic nerve head. We investigated the effect of a weekly application of brief ischemia pulses (ischemic conditioning) on the rat retinal damage induced by experimental glaucoma. Glaucoma was induced by weekly injections of chondroitin sulfate (CS) in the rat eye anterior chamber. Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 min; this maneuver started after 6 weekly injections of vehicle or CS and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. Glaucoma was evaluated in terms of: i) intraocular pressure (IOP), ii) retinal function (electroretinogram (ERG)), iii) visual pathway function (visual evoked potentials, (VEPs)) iv) histology of the retina and optic nerve head. Retinal thiobarbituric acid substances levels were assessed as an index of lipid peroxidation. Ischemic conditioning significantly preserved ERG, VEPs, as well as retinal and optic nerve head structure from glaucomatous damage, without changes in IOP. Moreover, ischemia pulses abrogated the increase in lipid peroxidation induced by experimental glaucoma. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies in glaucoma treatment. PMID:21887313

  7. Update on ischemic heart disease and critical care cardiology.

    PubMed

    Marín, Francisco; Díaz-Castro, Oscar; Ruiz-Nodar, Juan Miguel; García de la Villa, Bernardo; Sionis, Alessandro; López, Javier; Fernández-Ortiz, Antonio; Martínez-Sellés, Manuel

    2014-02-01

    This article summarizes the main developments reported in 2013 on ischemic heart disease, together with the most important innovations in the management of acute cardiac patients. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  8. Update on ischemic heart disease and intensive cardiac care.

    PubMed

    Sionis, Alessandro; Ruiz-Nodar, Juan Miguel; Fernández-Ortiz, Antonio; Marín, Francisco; Abu-Assi, Emad; Díaz-Castro, Oscar; Nuñez-Gil, Ivan J; Lidón, Rosa-Maria

    2015-03-01

    This article summarizes the main developments reported in 2014 on ischemic heart disease, together with the most important innovations in intensive cardiac care. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Electrocardiographic Left Atrial Abnormalities and Risk of Ischemic Stroke

    PubMed Central

    Kohsaka, Shun; Sciacca, Robert R.; Sugioka, Kenichi; Sacco, Ralph L.; Homma, Shunichi; Di Tullio, Marco R.

    2009-01-01

    Background and Purpose We evaluated the association between electrocardiographic left atrial abnormality (ECG-LAA) and ischemic stroke, especially whether ECG-LAA provides additional prognostic information to that provided by echocardiography. Methods A population-based, case-control study included 146 patients with first ischemic stroke and 195 age-, gender-, and race/ethnicity-matched community control subjects. ECG-LAA was defined as either P-wave duration >120 ms or P-terminal force in precordial lead V1 (PTFV1) >40 ms·mm. Results PTFV1 >40 ms·mm was associated with ischemic stroke after adjustment for other stroke risk factors (odds ratio [OR], 2.32; 95% CI, 1.29 to 4.18). The association remained significant after adding echocardiographic left atrial diameter to the model (OR, 2.31; 95% CI, 1.28 to 4.17). PTFV1 was independently associated with stroke in patients in the upper half of echocardiographically determined left ventricular mass (adjusted OR, 4.5; 95% CI, 2.20 to 9.15) but not in those in the lower half (OR, 0.58; 95% CI, 0.20 to 1.65; P=0.0008). Conclusions ECG-LAA can supplement 2D echocardiography in assessing the risk of ischemic stroke, especially in subjects with increased left ventricular mass. PMID:16210557

  10. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.

  11. Medications Used in the Treatment of Ischemic Heart Disease.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on medications used in the treatment of ischemic heart disease is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first.…

  12. Psychosocial Risk Factors Related to Ischemic Heart Disease in Women.

    PubMed

    Varghese, Tina; Hayek, Salim S; Shekiladze, Nikoloz; Schultz, William M; Wenger, Nanette K

    2016-01-01

    Psychosocial risk factors such as stress and psychiatric disorders are known to have negative impacts on health outcomes, but their effects on ischemic heart disease, particularly in women, remain to be fully understood despite contributing to one-third of the population attributable risk in acute myocardial infarction. The impact of stress, social isolation, low socioeconomic status, hostility and anger, and stress-related psychiatric disorders on cardiovascular outcomes and the potential mechanisms that underlie their association with ischemic heart disease, with a focus on women, is evaluated. Online search of relevant terms, including the aforementioned risk factors, women, and ischemic heart disease, was utilized to find recent and pertinent trials. Psychosocial risk factors increase cardiovascular risk in both women and men. However, current literature points to a greater degree of adverse cardiovascular events in women who experience these risk factors than in men, but the literature is not as well-defined as the data regarding traditional risk factors and cardiovascular disease. Dedicated study of the sex differences in ischemic heart disease incidence and recurrence, including the impact of psychosocial risk factors, is warranted for the development of appropriate gender-specific diagnostic testing and treatment options in heart disease.

  13. Remote limb ischemic conditioning enhances motor learning in healthy humans.

    PubMed

    Cherry-Allen, Kendra M; Gidday, Jeff M; Lee, Jin-Moo; Hershey, Tamara; Lang, Catherine E

    2015-06-01

    Brief bouts of sublethal ischemia have been shown to protect exposed tissue (ischemic conditioning) and tissues at remote sites (remote ischemic conditioning) against subsequent ischemic challenges. Given that the mechanisms of this protective phenomenon are multifactorial and epigenetic, we postulated that remote limb ischemic conditioning (RLIC) might enhance mechanisms responsible for neural plasticity, and thereby facilitate learning. Specifically, we hypothesized that conditioning of the nervous system with RLIC, achieved through brief repetitive limb ischemia prior to training, would facilitate the neurophysiological processes of learning, thus making training more effective and more long-lasting. Eighteen healthy adults participated in this study; nine were randomly allocated to RLIC and nine to sham conditioning. All subjects underwent seven consecutive weekday sessions and 2-wk and 4-wk follow-up sessions. We found that RLIC resulted in significantly greater motor learning and longer retention of motor performance gains in healthy adults. Changes in motor performance do not appear to be due to a generalized increase in muscle activation or muscle strength and were not associated with changes in serum brain-derived neurotrophic factor (BDNF) concentration. Of note, RLIC did not enhance cognitive learning on a hippocampus-dependent task. While future research is needed to establish optimal conditioning and training parameters, this inexpensive, clinically feasible paradigm might ultimately be implemented to enhance motor learning in individuals undergoing neuromuscular rehabilitation for brain injury and other pathological conditions.

  14. Expression profile based gene clusters for ischemic stroke detection.

    PubMed

    Adamski, Mateusz G; Li, Yan; Wagner, Erin; Yu, Hua; Seales-Bailey, Chloe; Soper, Steven A; Murphy, Michael; Baird, Alison E

    2014-09-01

    In microarray studies alterations in gene expression in circulating leukocytes have shown utility for ischemic stroke diagnosis. We studied forty candidate markers identified in three gene expression profiles to (1) quantitate individual transcript expression, (2) identify transcript clusters and (3) assess the clinical diagnostic utility of the clusters identified for ischemic stroke detection. Using high throughput next generation qPCR 16 of the 40 transcripts were significantly up-regulated in stroke patients relative to control subjects (p<0.05). Six clusters of between 5 and 7 transcripts were identified that discriminated between stroke and control (p values between 1.01e-9 and 0.03). A 7 transcript cluster containing PLBD1, PYGL, BST1, DUSP1, FOS, VCAN and FCGR1A showed high accuracy for stroke classification (AUC=0.854). These results validate and improve upon the diagnostic value of transcripts identified in microarray studies for ischemic stroke. The clusters identified show promise for acute ischemic stroke detection. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities.

    PubMed

    Rodrigo, Ramón; Fernández-Gajardo, Rodrigo; Gutiérrez, Rodrigo; Matamala, José Manuel; Carrasco, Rodrigo; Miranda-Merchak, Andrés; Feuerhake, Walter

    2013-08-01

    Stroke is the second leading cause of death, after ischemic heart disease, and accounts for 9% of deaths worldwide. According to the World Health Organization [WHO], 15 million people suffer stroke worldwide each year. Of these, more than 6 million die and another 5 million are permanently disabled. Reactive oxygen species [ROS] have been implicated in brain injury after ischemic stroke. There is evidence that a rapid increase in the production of ROS immediately after acute ischemic stroke rapidly overwhelm antioxidant defences, causing further tissue damage. These ROS can damage cellular macromolecules leading to autophagy, apoptosis, and necrosis. Moreover, the rapid restoration of blood flow increases the level of tissue oxygenation and accountsfor a second burst of ROS generation, which leads to reperfusion injury. Current measures to protect the brain against severe stroke damage are insufficient. Thus, it is critical to investigate antioxidant strategies that lead to the diminution of oxidative injury. The antioxidant vitamins C and E, the polyphenol resveratrol, the xanthine oxidase [XO] inhibitor allopurinol, and other antioxidant strategies have been reviewed in the setting of strokes. This review focuses on the mechanisms involved in ROS generation, the role of oxidative stress in the pathogenesis of ischemic stroke, and the novel therapeutic strategies to be tested to reduce the cerebral damage related to both ischemia and reperfusion.

  16. Collateral lessons from recent acute ischemic stroke trials.

    PubMed

    Liebeskind, David S

    2014-05-01

    Numerous acute ischemic stroke trials have recently published detailed results, providing an opportunity to consider the role of collaterals in stroke pathophysiology and their influential effect on patient outcomes. Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS), the largest randomized controlled trial of device therapy to date, tested the potential augmentation of collateral perfusion. SYNTHESIS Expansion, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE), and Interventional Management of Stroke (IMS) III chronicled the saga of endovascular therapy trialed against medical treatment for acute ischemic stroke. These recent randomized studies, however, largely neglect current device technology available for endovascular therapy as advanced by the TREVO2 and SOLITAIRE™(TM) FR With the Intention For Thrombectomy (SWIFT) studies. Such exhaustive efforts in recent trials have failed to introduce a new treatment for stroke that unequivocally improves patient outcomes. Collateral perfusion is widely recognized to vary across individuals in any population and exerts a dramatic effect on baseline variables including the time course of ischemic injury, stroke severity, imaging findings, and therapeutic opportunities. Similarly, collaterals have been recognized to influence recanalization, reperfusion, hemorrhagic transformation, and subsequent neurological outcomes after stroke. Collateral lessons may be gleaned from these trials, to expand consideration of overall study results and perhaps most importantly, alter ongoing and new trials in development. Detailed analyses of available information on collaterals from these trials demonstrate that collaterals may be more influential than the choice of treatment modality or intervention.

  17. Contraction of Blood Clots Is Impaired in Acute Ischemic Stroke.

    PubMed

    Tutwiler, Valerie; Peshkova, Alina D; Andrianova, Izabella A; Khasanova, Dina R; Weisel, John W; Litvinov, Rustem I

    2017-02-01

    Obstructive thrombi or thrombotic emboli are the pathogenic basis of ischemic stroke. In vitro blood clots and in vivo thrombi can undergo platelet-driven contraction (retraction), resulting in volume shrinkage. Clot contraction can potentially reduce vessel occlusion and improve blood flow past emboli or thrombi. The aim of this work was to examine a potential pathogenic role of clot contraction in ischemic stroke. We used a novel automated method that enabled us to quantify time of initiation and extent and rate of clot contraction in vitro. The main finding is that clot contraction from the blood of stroke patients was reduced compared with healthy subjects. Reduced clot contraction correlated with a lower platelet count and their dysfunction, higher levels of fibrinogen and hematocrit, leukocytosis, and other changes in blood composition that may affect platelet function and properties of blood clots. Platelets from stroke patents were spontaneously activated and displayed reduced responsiveness to additional stimulation. Clinical correlations with respect to severity and stroke pathogenesis suggest that the impaired clot contraction has the potential to be a pathogenic factor in ischemic stroke. The changeable ability of clots and thrombi to shrink in volume may be a novel unappreciated mechanism that aggravates or alleviates the course and outcomes of ischemic stroke. The clinical importance of clot or thrombus transformations in vivo and the diagnostic and prognostic value of this blood test for clot contraction need further exploration. © 2016 American Heart Association, Inc.

  18. Aortic atheromas in acute ischemic stroke patients in northern Israel.

    PubMed

    Telman, Gregory; Kouperberg, Efim; Sprecher, Elliot; Agmon, Yoram

    2012-01-01

    There are currently no data on ethnic differences in aortic atherosclerosis in Arab and Jewish patients from northern Israel with acute ischemic stroke. Data on demographic and risk factors alongside transesophageal echocardiography (TEE) data and treatment details for 509 patients with acute ischemic stroke were included in the study. The patients with aortic atheromas were older and had significantly more frequent vascular risk factors (hypertension, hyperlipidemia, and smoking), as well as vascular disease (ischemic heart disease, peripheral vascular disease, and carotid plaques). They were also treated with statins more often than those without aortic atheroma. Logistic regression analysis showed that age, smoking, ethnicity, and the presence of carotid plaques were independent predictors for aortic atheromas. Aortic plaques were found more frequently in Jewish patients than Arab patients (160 (41.9%) vs. 35 (27.3%); p= 0.003). This finding did not change after adjustment for age, sex, all vascular risk factors, and type of antithrombotic treatment. We did not find any difference between Arab and Jewish patients in the distribution of plaques by location or complexity before and after adjustment for age, sex, all vascular risk factors, or type of antithrombotic or lipid-lowering treatment. Our findings emphasize the influence of ethnicity on the prevalence of aortic atheromas in acute ischemic stroke patients in northern Israel. The search for genetic, cultural, socioeconomic, and other factors explaining these ethnic differences should be the topic of future studies.

  19. The effects of citicoline on acute ischemic stroke: a review.

    PubMed

    Overgaard, Karsten

    2014-08-01

    Early reopening of the occluded artery is, thus, important in ischemic stroke, and it has been calculated that 2 million neurons die every minute in an ischemic stroke if no effective therapy is given; therefore, "Time is Brain." In massive hemispheric infarction and edema, surgical decompression lowers the risk of death or severe disability defined as a modified Rankin Scale score greater than 4 in selected patients. The majority, around 80%-85% of all ischemic stroke victims, does not fulfill the criteria for revascularization therapy, and also for these patients, there is no effective acute therapy. Also there is no established effective acute treatment of spontaneous intracerebral bleeding. Therefore, an effective therapy applicable to all stroke victims is needed. The neuroprotective drug citicoline has been extensively studied in clinical trials with volunteers and more than 11,000 patients with various neurologic disorders, including acute ischemic stroke (AIS). The conclusion is that citicoline is safe to use and may have a beneficial effect in AIS patients and most beneficial in less severe stroke in older patients not treated with recombinant tissue plasminogen activator. No other neuroprotective agent had any beneficial effect in confirmative clinical trials or had any positive effect in the subgroup analysis. Citicoline is the only drug that in a number of different clinical stroke trials continuously had some neuroprotective benefit. Copyright © 2014. Published by Elsevier Inc.

  20. NLRP3 deficiency ameliorates neurovascular damage in experimental ischemic stroke.

    PubMed

    Yang, Fan; Wang, Ziying; Wei, Xinbing; Han, Huirong; Meng, Xianfang; Zhang, Yan; Shi, Weichen; Li, Fengli; Xin, Tao; Pang, Qi; Yi, Fan

    2014-04-01

    Although the innate immune response to induce postischemic inflammation is considered as an essential step in the progression of cerebral ischemia injury, the role of innate immunity mediator NLRP3 in the pathogenesis of ischemic stroke is unknown. In this study, focal ischemia was induced by middle cerebral artery occlusion in NLRP3(-/-), NOX2(-/-), or wild-type (WT) mice. By magnetic resonance imaging (MRI), Evans blue permeability, and electron microscopic analyses, we found that NLRP3 deficiency ameliorated cerebral injury in mice after ischemic stroke by reducing infarcts and blood-brain barrier (BBB) damage. We further showed that the contribution of NLRP3 to neurovascular damage was associated with an autocrine/paracrine pattern of NLRP3-mediated interleukin-1β (IL-1β) release as evidenced by increased brain microvessel endothelial cell permeability and microglia-mediated neurotoxicity. Finally, we found that NOX2 deficiency improved outcomes after ischemic stroke by mediating NLRP3 signaling. This study for the first time shows the contribution of NLRP3 to neurovascular damage and provides direct evidence that NLRP3 as an important target molecule links NOX2-mediated oxidative stress to neurovascular damage in ischemic stroke. Pharmacological targeting of NLRP3-mediated inflammatory response at multiple levels may help design a new approach to develop therapeutic strategies for prevention of deterioration of cerebral function and for the treatment of stroke.

  1. No influence of ischemic preconditioning on running economy.

    PubMed

    Kaur, Gungeet; Binger, Megan; Evans, Claire; Trachte, Tiffany; Van Guilder, Gary P

    2017-02-01

    Many of the potential performance-enhancing properties of ischemic preconditioning suggest that the oxygen cost for a given endurance exercise workload will be reduced, thereby improving the economy of locomotion. The aim of this study was to identify whether ischemic preconditioning improves exercise economy in recreational runners. A randomized sham-controlled crossover study was employed in which 18 adults (age 27 ± 7 years; BMI 24.6 ± 3 kg/m(2)) completed two, incremental submaximal (65-85% VO2max) treadmill running protocols (3 × 5 min stages from 7.2-14.5 km/h) coupled with indirect calorimetry to assess running economy following ischemic preconditioning (3 × 5 min bilateral upper thigh ischemia) and sham control. Running economy was expressed as mlO2/kg/km and as the energy in kilocalories required to cover 1 km of horizontal distance (kcal/kg/km). Ischemic preconditioning did not influence steady-state heart rate, oxygen consumption, minute ventilation, respiratory exchange ratio, energy expenditure, and blood lactate. Likewise, running economy was similar (P = 0.647) between the sham (from 201.6 ± 17.7 to 204.0 ± 16.1 mlO2/kg/km) and ischemic preconditioning trials (from 202.8 ± 16.2 to 203.1 ± 15.6 mlO2/kg/km). There was no influence (P = 0.21) of ischemic preconditioning on running economy expressed as the caloric unit cost (from 0.96 ± 0.12 to 1.01 ± 0.11 kcal/kg/km) compared with sham (from 1.00 ± 0.10 to 1.00 ± 0.08 kcal/kg/km). The properties of ischemic preconditioning thought to affect exercise performance at vigorous to severe exercise intensities, which generate more extensive physiological challenge, are ineffective at submaximal workloads and, therefore, do not change running economy.

  2. Ambient Air Pollution and the Risk of Acute Ischemic Stroke

    PubMed Central

    Wellenius, Gregory A.; Burger, Mary R.; Coull, Brent A.; Schwartz, Joel; Suh, Helen H.; Koutrakis, Petros; Schlaug, Gottfried; Gold, Diane R.; Mittleman, Murray A.

    2013-01-01

    Background The link between daily changes in ambient fine particulate matter air pollution (PM2.5) and cardiovascular morbidity and mortality is well established. Whether PM2.5 at levels below current US National Ambient Air Quality Standards also increases the risk of ischemic stroke remains uncertain. Methods We reviewed the medical records of 1705 Boston-area patients hospitalized with neurologist-confirmed ischemic stroke and abstracted data on the time of symptom onset and clinical characteristics. PM2.5 concentrations were measured at a central monitoring station. We used the time-stratified case-crossover study design to assess the association between the risk of ischemic stroke onset and PM2.5 levels in the hours and days preceding each event. We examined whether the association with PM2.5 differed by ischemic stroke etiology and patient characteristics. Results The estimated odds ratio of ischemic stroke onset was 1.34 (95% confidence interval (CI): 1.13, 1.58; p<0.001) following a 24-hour period classified as “moderate” (PM2.5 15–40 μg/m3) by the US Environmental Protection Agency’s (EPA) Air Quality Index compared to a 24-hour period classified as “good” (≤15 μg/m3). Considering PM2.5 as a continuous variable, the estimated odds ratio of ischemic stroke onset was 1.11 (95% CI: 1.03, 1.20; p=0.006) per interquartile range increase in PM2.5 (6.4 μg/m3). The increase in risk was greatest within 12–14 hours of exposure to PM2.5 and was most strongly associated with markers of traffic-related pollution. Conclusion These results suggest that exposure to PM2.5 levels considered generally safe by the US EPA increase the risk of ischemic stroke onset within hours of exposure. PMID:22332153

  3. Cardiac mast cell stabilization and cardioprotective effect of ischemic preconditioning in isolated rat heart.

    PubMed

    Parikh, V; Singh, M

    1998-05-01

    This study was designed to investigate the effect of disodium cromoglycate (DSCG), a mast cell stabilizer, on cardioprotective effect of ischemic preconditioning. Isolated rat heart was subjected to 30 min of global ischemia followed by 30 min of reperfusion. Ischemic preconditioning was provided by four episodes of 5-min global ischemia followed by 5 min of reperfusion before sustained ischemia. Ischemic preconditioning and DSCG (10 and 100 microM) treatment markedly decreased the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent and percentage incidence of ventricular premature beats (VPBs) and ventricular tachycardia/fibrillation (VT/VF) during reperfusion. Ischemic preconditioning and DSCG treatment also significantly reduced ischemia/reperfusion-induced mast cell peroxidase (MPO) release, a marker of mast cell degranulation. A significant increase in MPO release was observed immediately after ischemic preconditioning, and the release was found to be inhibited in hearts perfused with DSCG (10 and 100 microM) during ischemic preconditioning. DSCG administered during ischemic preconditioning (DSCG in ischemic preconditioning) attenuated the cardioprotective and antiarrhythmic effects of ischemic preconditioning. DSCG in ischemic preconditioning produced no marked effect on ischemia/reperfusion-induced MPO release. These findings tentatively suggest that DSCG administration during ischemic preconditioning abolishes its cardioprotective effect, perhaps by stabilizing resident cardiac mast cells.

  4. Advances in the Treatment of Ischemic Diseases by Mesenchymal Stem Cells

    PubMed Central

    Li, Shujing; Wang, Xianyun; Li, Jing; Zhang, Jun; Zhang, Fan; Hu, Jie; Qi, Yixin; Yan, Baoyong; Li, Quanhai

    2016-01-01

    Ischemic diseases are a group of diseases, including ischemic cerebrovascular disease, ischemic cardiomyopathy (ICM), and diabetic foot as well as other diseases which are becoming a leading cause of morbidity and mortality in the whole world. Mesenchymal stem cells (MSCs) have been used to treat a variety of ischemic diseases in animal models and clinical trials. Lots of recent publications demonstrated that MSCs therapy was safe and relieved symptoms in patients of ischemic disease. However, many factors could influence therapeutic efficacy including route of delivery, MSCs' survival and residential rate in vivo, timing of transplantation, particular microenvironment, and patient's clinical condition. In this review, the current status, therapeutic potential, and the detailed factors of MSCs-based therapeutics for ischemic cerebrovascular disease, ICM, and diabetic foot are presented and discussed. We think that MSCs transplantation would constitute an ideal option for patients with ischemic diseases. PMID:27293445

  5. Stem cell therapy in ischemic stroke: role of IV and intra-arterial therapy.

    PubMed

    Misra, Vivek; Ritchie, Michael M; Stone, Laura L; Low, Walter C; Janardhan, Vallabh

    2012-09-25

    Cell-based therapies are being investigated as an adjunct to IV thrombolysis or mechanical thrombectomy in ischemic stroke. This review summarizes the potential applications as well as challenges of intravascular cell delivery in ischemic stroke. We conducted a search of Medline as well as the clinicaltrials.gov Web site for all ongoing human clinical studies using stem cells in ischemic stroke patients. The pros and cons of the various donor cell types and routes of cell delivery, including intravascular delivery, in ischemic stroke are discussed. In addition, the potential challenges in translation from bench to bedside, the optimal techniques for intravascular cell delivery, and an updated comprehensive list of ongoing clinical trials in ischemic stroke are highlighted. Stem cells have shown a promising role in ischemic stroke, in preclinical studies as well as initial pilot studies. Further studies are needed to assess intravascular cell therapy as a potential adjunct to thrombolysis or mechanical thrombectomy in ischemic stroke.

  6. Healing of colonic ischemic anastomoses in the rat: role of superoxide radicals.

    PubMed

    Garcia, J G; Criado, F J; Persona, M A; Alonso, A G

    1998-07-01

    The aim of this study was to evaluate the role of superoxide radicals in the healing of ischemic colonic anastomoses in the rat. Adult male Wistar rats were used in a factorial design with two factors (normal or ischemic colonic anastomoses) each having two levels (treatment with saline or allopurinol). Colonic anastomoses were performed either in normal or previously devascularized colons (ischemic anastomoses) at identical locations, using the same technique. On the fourth postoperative day, animals were killed, and specimens were taken for determinations. Ischemic anastomoses displayed significant increases in superoxide radical (assayed as superoxide anion), superoxide dismutase, and glutathione peroxidase concentrations. Bursting strength and hydroxyproline levels were also significantly lower in these anastomoses. Allopurinol administration elicited a significant decrease in superoxide anions and raised both bursting strength and hydroxyproline levels only in ischemic anastomoses. Superoxide radicals are involved in the delay in healing of ischemic anastomoses. Allopurinol lowers superoxide anion production and has beneficial effects on the cicatrization of ischemic anastomoses.

  7. Etiologic Ischemic Stroke Phenotypes in the NINDS Stroke Genetics Network

    PubMed Central

    Ay, Hakan; Arsava, Ethem Murat; Andsberg, Gunnar; Benner, Thomas; Brown, Robert D.; Chapman, Sherita N.; Cole, John W.; Delavaran, Hossein; Dichgans, Martin; Engström, Gunnar; Giralt-Steinhauer, Eva; Grewal, Raji P.; Gwinn, Katrina; Jern, Christina; Jimenez-Conde, Jordi; Jood, Katarina; Katsnelson, Michael; Kissela, Brett; Kittner, Steven J.; Kleindorfer, Dawn O.; Labovitz, Daniel L.; Lanfranconi, Silvia; Lee, Jin-Moo; Lehm, Manuel; Lemmens, Robin; Levi, Chris; Li, Linxin; Lindgren, Arne; Markus, Hugh S.; McArdle, Patrick F.; Melander, Olle; Norrving, Bo; Peddareddygari, Leema Reddy; Pedersén, Annie; Pera, Joanna; Rannikmäe, Kristiina; Rexrode, Kathryn M.; Rhodes, David; Rich, Stephen S.; Roquer, Jaume; Rosand, Jonathan; Rothwell, Peter M.; Rundek, Tatjana; Sacco, Ralph L.; Schmidt, Reinhold; Schürks, Markus; Seiler, Stephan; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie; Thijs, Vincent; Woodfield, Rebecca; Worrall, Bradford B.; Meschia, James F.

    2014-01-01

    Background and Purpose NINDS Stroke Genetics Network (SiGN) is an international consortium of ischemic stroke studies that aims to generate high quality phenotype data to identify the genetic basis of etiologic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. Methods Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major etiologic groups without weighting towards the most likely cause) and causative ischemic stroke subtypes in 16,954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded re-adjudication of 1509 randomly selected cases. Results The distribution of etiologic categories varied by study, age, sex, and race (p<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke etiology (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (kappa 0.72, 95%CI:0.69-0.75) and phenotypic classifications (kappa 0.73, 95%CI:0.70-0.75). Conclusions This study demonstrates that etiologic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a stroke patient does not necessarily mean that it is the cause of stroke. PMID:25378430

  8. The role of HIF in cobalt-induced ischemic tolerance.

    PubMed

    Jones, S M; Novak, A E; Elliott, J P

    2013-11-12

    Understanding the endogenous survival pathways induced by ischemic tolerance may yield targets for neuroprotection from stroke. One well-studied pathway reported to be evoked by preconditioning stimuli is the transcription factor HIF (hypoxia-inducible factor). However, whether HIF induction by ischemic insults is neuroprotective or toxic is still unclear. We examined the ability of three prolyl-hydroxylase inhibitors, which induce HIF, to protect hippocampal cultures from oxygen-glucose deprivation. Hippocampal cultures were exposed to ischemic preconditioning or various concentrations of cobalt chloride, deferoxamine (DFO) or dimethyloxylalyglycine (DMOG), prior to lethal oxygen-glucose deprivation (OGD). Cell survival of neurons and astrocytes was determined with dual-label immunocytochemistry. The induction of HIF targets was assessed in mixed as well as astrocyte-enriched cultures. Ischemic preconditioning, as well as low concentrations of cobalt and DFO, enhanced the survival of neurons following OGD. However, DMOG exacerbates OGD-induced neuronal death. At low concentrations, all three prolyl-hydroxylase (PHD) inhibitors increased the survival of astrocytes. Neuroprotective concentrations of cobalt induced the transcription of the cytokine erythropoietin (EPO) in astrocyte cultures. In addition, pretreatment with recombinant human erythropoietin (rH-EPO) also protected neurons from OGD. Our data suggest that HIF-induced EPO, released from astrocytes, protects neurons from OGD. However, the three PHD inhibitors each exhibited different neuroprotective profiles at low concentrations, suggesting that not all PHD inhibitors are created equal. The protective effects at low doses is reminiscent of HIF involvement in ischemic tolerance, in which sub-lethal insults induce HIF pathways resulting in neuroprotection, whereas the high-dose toxicity suggests that over-activation of HIF is not always protective. Therefore, the choice of inhibitor and dose may determine

  9. Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients

    SciTech Connect

    Lee, Ching-Chih; Su, Yu-Chieh; Ho, Hsu-Chueh; Hung, Shih-Kai; Lee, Moon-Sing; Chiou, Wen-Yen; Chou, Pesus; Huang, Yung-Sung

    2011-12-01

    Purpose: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. Methods and Materials: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n = 1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n = 4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival rate between the two cohorts after adjusting for possible confounding and risk factors. Results: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35-54 had a 1.66 times (95% CI, 1.16-2.86; p = 0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55-64 years (hazard ratio = 0.87; 95% CI, 0.56-1.33; p = 0.524) after adjusting for other factors. Conclusions: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.

  10. Disruption of thrombospondin-2 accelerates ischemic fracture healing.

    PubMed

    Miedel, Emily; Dishowitz, Michael I; Myers, Marc H; Dopkin, Derek; Yu, Yan-Yiu; Miclau, Ted S; Marcucio, Ralph; Ahn, Jaimo; Hankenson, Kurt D

    2013-06-01

    Thrombospondin-2 (TSP2) is a matricellular protein that is highly up-regulated during fracture healing. TSP2 negatively regulates vascularity, vascular reperfusion following ischemia, and cutaneous wound healing. As well, TSP2-null mice show increased endocortical bone formation due to an enhanced number of mesenchymal progenitor cells and show increased cortical thickness. Mice deficient in TSP2 (TSP2-null) show an alteration in fracture healing, that is unrelated to their cortical bone phenotype, which is characterized by enhanced vascularization with a shift towards an intramembranous healing phenotype; thus, we hypothesized that there would be enhanced ischemic fracture healing in the absence of TSP2. We investigated whether an absence of TSP2 would enhance ischemic fracture healing utilizing Laser doppler, µCT and histological analysis. Ischemic tibial fractures were created in wildtype (WT) and TSP2-null mice and harvested 10, 20, or 40 days post-fracture. TSP2-null mice show enhanced vascular perfusion following ischemic fracture. At day 10 post-fracture, TSP2-null mice have 115% greater bone volume than WT mice. This is associated with a 122% increase in vessel density, 20% increase in cell proliferation, and 15% decrease in apoptosis compared to WT. At day 20, TSP2-null mice have 34% more bone volume, 51% greater bone volume fraction, and 37% more bone tissue mineral density than WT. By 40 days after fracture the TSP2-null mice have a 24% increase in bone volume fraction, but other parameters show no significant differences. These findings indicate TSP2 is a negative regulator of ischemic fracture healing and that in the absence of TSP2 bone regeneration is enhanced.

  11. Frequency of craniofacial pain in patients with ischemic heart disease

    PubMed Central

    Bakhshi, Mahin; Rezaei, Rezvan; Baharvand, Maryam

    2017-01-01

    Background Referred craniofacial pain of cardiac origin might be the only symptom of ischemic heart accidents. This study aimed to determine the frequency of craniofacial pain in patients with ischemic heart disease. Material and Methods This cross-sectional study was accomplished on 296 patients who met the criteria of having ischemic heart disease. Data regarding demographics, medical history and referred craniofacial pain were recorded in data forms. In addition, patients underwent oral examination to preclude any source of dental origin. Chi-square test, Student’s t-test and backward regression model were used to analyze the data by means of SPSS software version 21. P<0.05 was considered significant. Results A total of 296 patients were studied comprising of 211 men (71%) and 85 women (29%) with the mean age of 55.8. Craniofacial pain was experienced by 53 patients out of 296, 35 (66%) of whom were male and 18 (34%) were female. None of the patients experienced craniofacial pain solely. The most common sites of craniofacial pain were occipital and posterior neck (52.8%), head (43.3%), throat and anterior neck (41.5%) respectively. We found no relationship between craniofacial pain of cardiac origin with age, diabetes, hypertension, and family history. On the other hand, there was a significant relationship between hyperlipidemia and smoking with craniofacial pain of cardiac origin. Conclusions Radiating pain to face and head can be expected quite commonly during a cardiac ischemic event. Dental practitioners should be thoroughly aware of this symptomatology to prevent misdirected dental treatment and delay of medical care. Key words:Craniofacial pain, ischemic heart disease, myocardial infarction, angina pectoris, referred pain. PMID:28149470

  12. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack.

    PubMed

    Johnston, S Claiborne; Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Jonasson, Jenny; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence

    2016-07-07

    Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia. We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days. During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%. In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).

  13. Racial Difference in Cerebral Microbleed Burden among Ischemic Stroke Patients.

    PubMed

    Shahjouei, Shima; Tsivgoulis, Georgios; Singh, Mantinderpreet; McCormack, Michael; Noorbakhsh-Sabet, Nariman; Goyal, Nitin; Alexandrov, Anne W; Alexandrov, Andrei V; Zand, Ramin

    2017-08-21

    Data on the epidemiology of cerebral microbleeds (CMBs) among patients with ischemic stroke are limited. This study compared the number, associated factors, and topography of CMBs between African American and Caucasian ischemic stroke patients in the Mid-South United States. We evaluated consecutive ischemic stroke patients admitted to our tertiary stroke center, University of Tennessee Health Science Center, Memphis, Tennessee, in a two-year period. We analyzed T2*-weighted magnetic resonance images for the number, location, and topography of CMBs, as well as patients' demographic and clinical information. Among 760 ischemic stroke patients who were included (mean age was 62.1 ± 13.9 years, 51.4% men), 450 (59.2%) were African American. In comparison with Caucasians, African Americans were about five years younger (P = .000) and had a higher rate of hypertension (80.9% vs. 74.5%, P = .036). Similarly, African Americans had a higher prevalence of diabetes mellitus (P = .001). There was no significant difference between African-Americans and Caucasians in terms of CMBs presence and location. African Americans had a higher number of CMBs in comparison with Caucasians, but the difference was not significant. African Americans were more likely to have CMBs ≥5 (P = .047). Although African American stroke patients had a higher rate of large confluent white matter lesions, there was no significant racial difference regarding the rate and severity of deep white matter lesions. We did not observe any differences between African American and Caucasian patients with ischemic stroke patients regarding the presence, number, and location of CMBs. However, our results suggested that the prevalence of multiple CMBs (CMBs ≥5) might be higher among African American stroke patients. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Ischemic stroke and heart failure: facts and numbers.

    PubMed

    Scherbakov, Nadja; Haeusler, Karl Georg; Doehner, Wolfram

    2015-03-01

    Heart failure (HF) is pandemic in the modern society. Comorbidities of HF come increasingly to the fore in today's patient presentation and demand multidisciplinary treatment concepts. Ischemic stroke is a major comorbidity in HF patients and frequently contributes to the adverse outcome and functional dependency. Patients with HF are two-fold to three-fold more likely to suffer an ischemic stroke, have more than two times higher mortality and show worse functional outcome after stroke compared with non-HF subjects. The risk of recurrent stroke is about two-fold elevated in patients with HF. The risk of stroke increased with time duration of HF from 18 per 100 cases in the first year of HF to 47 per 1000 patients within the next 4-5 years. Moreover, so called 'silent' strokes (clinically asymptomatic brain lesions) are two to four times more likely in HF patients. In turn, 10-24% of stroke patients have HF. Specific characteristics of the interaction between ischemic stroke and HF have been uncovered in recent years. However, gaps in present knowledge need to be addressed in future studies. What are the detailed pathophysiologic links beyond atrial fibrillation, stroke patterns, and time courses in the interaction? What implication has HF with preserved versus reduced ejection fraction? Does treatment of HF prevents ischemic stroke or reduces stroke-related sequelae? This editorial provides a condensed overview on current insights and presents facts and numbers on the interaction between heart failure and ischemic stroke. © 2015 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

  15. Hyperglycemia predicts poststroke infections in acute ischemic stroke.

    PubMed

    Zonneveld, Thomas P; Nederkoorn, Paul J; Westendorp, Willeke F; Brouwer, Matthijs C; van de Beek, Diederik; Kruyt, Nyika D

    2017-04-11

    To investigate whether admission hyperglycemia predicts poststroke infections and, if so, whether poststroke infections modify the effect of admission hyperglycemia on functional outcome in ischemic stroke. We used data from acute ischemic stroke patients in the Preventive Antibiotics in Stroke Study (PASS), a multicenter randomized controlled trial (n = 2,550) investigating the effect of preventive antibiotics on functional outcome. Admission hyperglycemia was defined as blood glucose ≥7.8 mmol/L and poststroke infection as any infection during admission judged by an expert adjudication committee. Functional outcome at 3 months was assessed with the modified Rankin Scale. Of 1,676 nondiabetic ischemic stroke patients, 338 (20%) had admission hyperglycemia. After adjustment for potential confounding variables, admission hyperglycemia was associated with poststroke infection (adjusted odds ratio [aOR] 2.31, 95% CI 1.31-4.07), worse 3-month functional outcome (common aOR 1.40, 95% CI 1.12-1.73), and 3-month mortality (aOR 2.11, 95% CI 1.40-3.19). Additional adjustment for poststroke infection in the functional outcome analysis, done to assess poststroke infection as an intermediate in the pathway from admission hyperglycemia to functional outcome, did not substantially change the model. In patients with recorded diabetes mellitus (n = 418), admission hyperglycemia was not associated with poststroke infection (aOR 0.49, 95% CI 0.15-1.58). In nondiabetic acute ischemic stroke patients, admission hyperglycemia is associated with poststroke infection and worse functional outcome. Poststroke infections did not modify the effect of admission hyperglycemia on functional outcome in ischemic stroke. © 2017 American Academy of Neurology.

  16. Use of susceptibility-weighted imaging in assessing ischemic penumbra

    PubMed Central

    Wu, Xiujuan; Luo, Song; Wang, Ying; Chen, Yang; Liu, Jun; Bai, Jing; Feng, Jiachun; Zhang, Hongliang

    2017-01-01

    Abstract Rationale: The ischemic penumbra assessment is essential for the subsequent therapy and prediction of evolution in patients with acute ischemic infraction. Although controversial as a perfect equivalence to penumbra, perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch may predict the response to thrombolysis. Due to the reliance of PWI on contrast agents, noninvasive alternatives remain an unmet need. Patient concerns: We reported a 65-year-old man complained of paroxysmal hemiplegia of his right limbs and anepia for 2 days, whereas the symptoms lasted for about 12 hours when he admitted to the hospital. Diagnosis: We diagnosed it as acute ischemic stroke caused by the left middle cerebral artery stenosis. Interventions: Susceptibility-weighted imaging (SWI), multimodal magnetic resonance imaging (MRI) work-up which includes conventional MRI sequences (T1WI, T2WI, and FLAIR), DWI, PWI. Outcomes: His DWI-SWI mismatch was comparable to that of DWI-PWI at admission, suggesting that DWI-SWI could predict ischemic penumbra in patient with acute infarction. He refused the digital subtraction angiography examination or stenting, and he was treated with aspirin, atorvastain, and supportive treatment. The patient received a reexamination of the conventional MRI and SWI 11 days later. Expansion of the infarction in the affected MCA territory resulted from the penumbra indicated by the mismatch between DWI-SWI. Lessons: SWI can be used as a noninvasive alternative to evaluate the ischemic penumbra. Besides, SWI can provide perfusion information comparable to PWI and SWI is sufficient to identify occlusive arteries. PMID:28178170

  17. Migraine and Cerebrovascular Atherosclerosis in Patients With Ischemic Stroke.

    PubMed

    van Os, Hendrikus J A; Mulder, Inge A; Broersen, Alexander; Algra, Ale; van der Schaaf, Irene C; Kappelle, L Jaap; Velthuis, Birgitta K; Terwindt, Gisela M; Schonewille, Wouter J; Visser, Marieke C; Ferrari, Michel D; van Walderveen, Marianne A A; Wermer, Marieke J H

    2017-07-01

    Migraine is a well-established risk factor for ischemic stroke, but migraine is also related to other vascular diseases. This study aims to investigate the association between migraine and cerebrovascular atherosclerosis in patients with acute ischemic stroke. We retrieved data on patients with ischemic stroke from the DUST (Dutch Acute Stroke Study). Migraine history was assessed with a migraine screener and confirmed by telephone interview based on the ICHD criteria (International Classification of Headache Disorders). We assessed intra- and extracranial atherosclerotic changes and quantified intracranial internal carotid artery calcifications as measure of atherosclerotic burden on noncontrast computed tomography and computed tomographic angiography. We calculated risk ratios with adjustments for possible confounders with multivariable Poisson regression analyses. We included 656 patients, aged 18 to 99 years, of whom 53 had a history of migraine (29 with aura). Patients with migraine did not have more frequent atherosclerotic changes in intracranial (51% versus 74%; adjusted risk ratio, 0.82; 95% confidence interval, 0.64-1.05) or extracranial vessels (62% versus 79%; adjusted risk ratio, 0.93; 95% confidence interval, 0.77-1.12) than patients without migraine and had comparable internal carotid artery calcification volumes (largest versus medium and smallest volume tertile, 23% versus 35%; adjusted risk ratio, 0.93; 95% confidence interval, 0.57-1.52). Migraine is not associated with excess atherosclerosis in large vessels in patients with acute ischemic stroke. Our findings suggest that the biological mechanisms by which migraine results in ischemic stroke are not related to macrovascular cerebral atherosclerosis. © 2017 American Heart Association, Inc.

  18. Ischemic Stroke in Young Adults and Preexisting Psychiatric Disorders

    PubMed Central

    Chiu, Yu-Chuan; Bai, Ya-Mei; Su, Tung-Ping; Chen, Tzeng-Ji; Chen, Mu-Hong

    2015-01-01

    Abstract Previous studies showed that psychiatric disorders such as major depression, bipolar disorders, and alcohol misuse are associated with an increased risk of ischemic stroke. However, the link between psychiatric disorders and stroke in the young population is rarely investigated. Using the Taiwan National Health Insurance Research Database, 2063 young adults aged between 18 and 45 years with ischemic stroke and 8252 age- and sex-matched controls were enrolled in our study between 1998 and 2011. Participants who had preexisting psychiatric disorders were identified. After adjusting for preexisting physical disorders and demographic data, patients with ischemic stroke had an increased risk of having preexisting psychiatric disorders, including bipolar disorder (odds ratio [OR]: 2.23, 95% confidence interval [CI]: 1.06∼4.67), unipolar depression (OR: 2.15, 95% CI: 1.62∼2.86), anxiety disorders (OR: 2.63, 95% CI: 1.87∼3.69), and alcohol use disorders (OR: 2.86, 95% CI: 1.79∼4.57). Young ischemic stroke (age ≥30 years) was related to the risk of preexisting unipolar depression (OR: 1.49, 95% CI: 1.05∼2.11), anxiety disorders (OR: 1.99, 95% CI: 1.33∼2.97), and alcohol use disorders (OR: 2.54, 95% CI: 1.55∼4.14); very young stroke (age <30 years) was only associated with the risk of preexisting unipolar depression (OR: 4.15, 95% CI: 1.47∼11.72). Patients who had experienced ischemic stroke at age younger than 45 years had a higher risk of having pre-existing bipolar disorder, unipolar depression, anxiety disorders, and alcohol use disorders than those who did not after adjusting for demographic data and stroke-related medical comorbidities. PMID:26402806

  19. Expression profile based gene clusters for ischemic stroke detection Whole blood gene clusters for ischemic stroke detection

    PubMed Central

    Adamski, Mateusz G; Li, Yan; Wagner, Erin; Yu, Hua; Seales-Bailey, Chloe; Soper, Steven A; Murphy, Michael; Baird, Alison E

    2014-01-01

    In microarray studies alterations in gene expression in circulating leukocytes have shown utility for ischemic stroke diagnosis. We studied forty candidate markers identified in three gene expression profiles to (1) quantitate individual transcript expression, (2) identify transcript clusters and (3) assess the clinical diagnostic utility of the clusters identified for ischemic stroke detection. Using high throughput next generation qPCR 16 of the 40 transcripts were significantly up-regulated in stroke patients relative to control subjects (p<0.05). Six clusters of between 5 and 7 transcripts discriminated between stroke and control (p values between 1.01e-9 and 0.03). A 7 transcript cluster containing PLBD1, PYGL, BST1, DUSP1, FOS, VCAN and FCGR1A showed high accuracy for stroke classification (AUC=0.854). These results validate and improve upon the diagnostic value of transcripts identified in microarray studies for ischemic stroke. The clusters identified show promise for acute ischemic stroke detection. PMID:25135788

  20. Detection of paroxysmal atrial fibrillation or flutter in patients with acute ischemic stroke or transient ischemic attack by Holter monitoring.

    PubMed

    Thakkar, Sandeep; Bagarhatta, Rajeev

    2014-01-01

    Paroxysmal atrial fibrillation and flutter are strong risk factors for stroke. Due to high recurrence rate of ischemic events and given the benefit of oral anticoagulation over antiplatelet drugs, it is important to identify this arrhythmia. Unfortunately, paroxysmal AF or flutter is asymptomatic in majority and therefore, difficult to detect. Consecutive patients presenting with symptoms of acute ischemic stroke or transient ischemic attack were included. All patients free of AF or flutter on presentation underwent 24 h Holter monitoring within 7 days of admission. Overall, fifty two (52) patients (mean age 59.51 ± 13.45 years) with acute stroke (80.8%) and TIA (19.8%) underwent 24 h Holter monitoring. Paroxysmal AF was detected in 3 cases (5.8%), all 3 patients had acute stroke and were older than age 60 years. Type of stroke was the only factor which was associated with greater risk of having paroxysmal AF or flutter, AF accounted for 50% cases (2 out of 4) of clinically suspected cardio embolic stroke. Screening consecutive patients with ischemic stroke with routine Holter monitoring will identify new atrial fibrillation/flutter in approximately one in 17 patients. Older age and type of stroke are strongly associated with increased risk. By carefully selecting the patients, the detection rates could be further increased. Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  1. Development and Validation of Electronic Quality Measures to Assess Care for Patients With Transient Ischemic Attack and Minor Ischemic Stroke.

    PubMed

    Bravata, Dawn M; Myers, Laura J; Cheng, Eric; Reeves, Mathew; Baye, Fitsum; Yu, Zhangsheng; Damush, Teresa; Miech, Edward J; Sico, Jason; Phipps, Michael; Zillich, Alan; Johanning, Jason; Chaturvedi, Seemant; Austin, Curt; Ferguson, Jared; Maryfield, Bailey; Snow, Kathy; Ofner, Susan; Graham, Glenn; Rhude, Rachel; Williams, Linda S; Arling, Greg

    2017-09-01

    Despite interest in using electronic health record (EHR) data to assess quality of care, the accuracy of such data is largely unknown. We sought to develop and validate transient ischemic attack and minor ischemic stroke electronic quality measures (eQMs) using EHR data. A random sample of patients with transient ischemic attack or minor ischemic stroke, cared for in Veterans Health Administration facilities (fiscal year 2011), was identified. We constructed 31 eQMs based on existing quality measures. Chart review was the criterion standard for validating the eQMs. To evaluate eQMs in terms of eligibility, we calculated the proportion of patients who were genuinely not eligible to receive a process (based on chart review) and who were correctly identified as not eligible by the EHR data (specificity). To assess eQMs about classification of whether patients received a process, we calculated the proportion of patients who actually received the process (based on chart review) and who were classified correctly by the EHR data as passing (sensitivity). Seven hundred sixty-three patients were included. About eligibility, specificity varied from 25% (brain imaging; carotid imaging) to 99% (anticoagulation quality). About pass rates, sensitivity varied from 30% (antihypertensive class) to 100% (coronary risk assessment; international normalized ratio measured). The 16 eQMs with ≥70% specificity in eligibility and ≥70% sensitivity in pass rates included coronary risk assessment, international normalized ratio measured, HbA1c measurement, speech language pathology consultation, anticoagulation for atrial fibrillation, discharge on statin, lipid management, neurology consultation, Holter, deep vein thrombosis prophylaxis, oral hypoglycemic intensification, cholesterol medication intensification, antihypertensive intensification, antihypertensive class, carotid stenosis intervention, and substance abuse referral for alcohol. It is feasible to construct valid eQMs for

  2. Statin Prescription Adhered to Guidelines for Patients Hospitalized due to Acute Ischemic Stroke or Transient Ischemic Attack

    PubMed Central

    Hong, Keun-Sik; Oh, Mi Sun; Choi, Hye-Yeon; Cho, A-Hyun; Kwon, Hyung-Min; Yu, Kyung-Ho; Bae, Hee-Joon; Lee, Juneyoung

    2013-01-01

    Background and Purpose Secondary stroke prevention guidelines recommend statins for the management of dyslipidemia in ischemic stroke and transient ischemic attack (TIA). This study assessed the guideline-based statin prescription (GBSP) rate in Korea and the associated physician and patient factors. Methods A survey was conducted to assess Korean neurologists' knowledge of and attitude toward the current dyslipidemia management guidelines. The characteristics and discharge statin prescription for all consecutive patients with acute ischemic stroke or TIA treated by participating neurologists during the 6 months prior to the survey were abstracted. Using algorithms to determine GBSP, we assessed the rate and independent factors of GBSP. Results Of the 174 participating neurologists, 79 (45.4%) were categorized as a higher-level knowledge group. For the 4407 patients (mean age, 66.4 years; female, 42.5%; 90.6% with ischemic stroke and 9.4% with TIA) enrolled in this study, the GBSP rate at discharge was 78.6%. The GBSP rate increased significantly with increasing physician knowledge level (test for trend, p<0.0001), and was higher among patients treated by the higher-level knowledge group than for those treated by the lower-level knowledge group (81.6% vs. 74.7%; unadjusted p<0.0001 and adjusted p=0.045). Other independent factors associated with a higher GBSP rate were hypercholesterolemia and higher low-density lipoprotein cholesterol level, while those associated with a lower GBSP rate were cardioembolism, undetermined etiology due to negative or incomplete work-up, other determined etiology, and TIA presentation. Conclusions More than three-quarters of acute ischemic stroke survivors and TIA patients receive a GBSP at discharge, and this proportion would be further improved by improving the knowledge of dyslipidemia management guidelines among neurologists. PMID:24285962

  3. Remote ischemic perconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke: a randomized trial.

    PubMed

    Hougaard, Kristina Dupont; Hjort, Niels; Zeidler, Dora; Sørensen, Leif; Nørgaard, Anne; Hansen, Troels Martin; von Weitzel-Mudersbach, Paul; Simonsen, Claus Z; Damgaard, Dorte; Gottrup, Hanne; Svendsen, Kristina; Rasmussen, Peter Vestergaard; Ribe, Lars R; Mikkelsen, Irene K; Nagenthiraja, Kartheban; Cho, Tae-Hee; Redington, Andrew N; Bøtker, Hans Erik; Østergaard, Leif; Mouridsen, Kim; Andersen, Grethe

    2014-01-01

    Remote ischemic preconditioning is neuroprotective in models of acute cerebral ischemia. We tested the effect of prehospital rPerC as an adjunct to treatment with intravenous alteplase in patients with acute ischemic stroke. Open-label blinded outcome proof-of-concept study of prehospital, paramedic-administered rPerC at a 1:1 ratio in consecutive patients with suspected acute stroke. After neurological examination and MRI, patients with verified stroke receiving alteplase treatment were included and received MRI at 24 hours and 1 month and clinical re-examination after 3 months. The primary end point was penumbral salvage, defined as the volume of the perfusion-diffusion mismatch not progressing to infarction after 1 month. Four hundred forty-three patients were randomized after provisional consent, 247 received rPerC and 196 received standard treatment. Patients with a nonstroke diagnosis (n=105) were excluded from further examinations. The remaining patients had transient ischemic attack (n=58), acute ischemic stroke (n=240), or hemorrhagic stroke (n=37). Transient ischemic attack was more frequent (P=0.006), and National Institutes of Health Stroke Scale score on admission was lower (P=0.016) in the intervention group compared with controls. Penumbral salvage, final infarct size at 1 month, infarct growth between baseline and 1 month, and clinical outcome after 3 months did not differ among groups. After adjustment for baseline perfusion and diffusion lesion severity, voxelwise analysis showed that rPerC reduced tissue risk of infarction (P=0.0003). Although the overall results were neutral, a tissue survival analysis suggests that prehospital rPerC may have immediate neuroprotective effects. Future clinical trials should take such immediate effects, and their duration, into account. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00975962.

  4. The complexity of atrial fibrillation newly diagnosed after ischemic stroke and transient ischemic attack: advances and uncertainties

    PubMed Central

    Cerasuolo, Joshua O.; Cipriano, Lauren E.; Sposato, Luciano A.

    2017-01-01

    Purpose of review Atrial fibrillation is being increasingly diagnosed after ischemic stroke and transient ischemic attack (TIA). Patient characteristics, frequency and duration of paroxysms, and the risk of recurrent ischemic stroke associated with atrial fibrillation detected after stroke and TIA (AFDAS) may differ from atrial fibrillation already known before stroke occurrence. We aim to summarize major recent advances in the field, in the context of prior evidence, and to identify areas of uncertainty to be addressed in future research. Recent findings Half of all atrial fibrillations in ischemic stroke and TIA patients are AFDAS, and most of them are asymptomatic. Over 50% of AFDAS paroxysms last less than 30 s. The rapid initiation of cardiac monitoring and its duration are crucial for its timely and effective detection. AFDAS comprises a heterogeneous mix of atrial fibrillation, possibly including cardiogenic and neurogenic types, and a mix of both. Over 25 single markers and at least 10 scores have been proposed as predictors of AFDAS. However, there are considerable inconsistencies across studies. The role of AFDAS burden and its associated risk of stroke recurrence have not yet been investigated. Summary AFDAS may differ from atrial fibrillation known before stroke in several clinical dimensions, which are important for optimal patient care strategies. Many questions remain unanswered. Neurogenic and cardiogenic AFDAS need to be characterized, as it may be possible to avoid some neurogenic cases by initiating timely preventive treatments. AFDAS burden may differ in ischemic stroke and TIA patients, with distinctive diagnostic and treatment implications. The prognosis of AFDAS and its risk of recurrent stroke are still unknown; therefore, it is uncertain whether AFDAS patients should be treated with oral anticoagulants. PMID:27984303

  5. Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery.

    PubMed

    Hausenloy, Derek J; Candilio, Luciano; Evans, Richard; Ariti, Cono; Jenkins, David P; Kolvekar, Shyam; Knight, Rosemary; Kunst, Gudrun; Laing, Christopher; Nicholas, Jennifer; Pepper, John; Robertson, Steven; Xenou, Maria; Clayton, Tim; Yellon, Derek M

    2015-10-08

    Whether remote ischemic preconditioning (transient ischemia and reperfusion of the arm) can improve clinical outcomes in patients undergoing coronary-artery bypass graft (CABG) surgery is not known. We investigated this question in a randomized trial. We conducted a multicenter, sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG (with or without valve surgery) with blood cardioplegia. After anesthesia induction and before surgical incision, patients were randomly assigned to remote ischemic preconditioning (four 5-minute inflations and deflations of a standard blood-pressure cuff on the upper arm) or sham conditioning (control group). Anesthetic management and perioperative care were not standardized. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, coronary revascularization, or stroke, assessed 12 months after randomization. We enrolled a total of 1612 patients (811 in the control group and 801 in the ischemic-preconditioning group) at 30 cardiac surgery centers in the United Kingdom. There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote ischemic preconditioning group and those in the control group (212 patients [26.5%] and 225 patients [27.7%], respectively; hazard ratio with ischemic preconditioning, 0.95; 95% confidence interval, 0.79 to 1.15; P=0.58). Furthermore, there were no significant between-group differences in either adverse events or the secondary end points of perioperative myocardial injury (assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours), inotrope score (calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery), acute kidney injury, duration of stay in the intensive care unit and hospital, distance on the 6-minute walk test, and quality of life

  6. Stress hyperglycemia and acute ischemic stroke in-hospital outcome.

    PubMed

    Tziomalos, Konstantinos; Dimitriou, Panagiotis; Bouziana, Stella D; Spanou, Marianna; Kostaki, Stavroula; Angelopoulou, Stella-Maria; Papadopoulou, Maria; Giampatzis, Vasilios; Savopoulos, Christos; Hatzitolios, Apostolos I

    2017-02-01

    Stress hyperglycemia is frequent in patients with acute ischemic stroke. However, it is unclear whether stress hyperglycemia only reflects stroke severity or if it is directly associated with adverse outcome. We aimed to evaluate the prognostic significance of stress hyperglycemia in acute ischemic stroke. We prospectively studied 790 consecutive patients who were admitted with acute ischemic stroke (41.0% males, age 79.4±6.8years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Stress hyperglycemia was defined as fasting serum glucose levels at the second day after admission ≥126mg/dl in patients without type 2 diabetes mellitus (T2DM). The outcome was assessed with adverse outcome rates at discharge (modified Rankin scale between 2 and 6) and with in-hospital mortality. In the total study population, 8.6% had stress hyperglycemia. Patients with stress hyperglycemia had more severe stroke. Independent predictors of adverse outcome at discharge were age, prior ischemic stroke and NIHSS at admission whereas treatment with statins prior to stroke was associated with favorable outcome. When the NIHSS was removed from the multivariate model, independent predictors of adverse outcome were age, heart rate at admission, prior ischemic stroke, log-triglyceride (TG) levels and stress hyperglycemia, whereas treatment with statins prior to stroke was associated with favorable outcome. Independent predictors of in-hospital mortality were atrial fibrillation (AF), diastolic blood pressure (DBP), serum log-TG levels and NIHSS at admission. When the NIHSS was removed from the multivariate model, independent predictors of in-hospital mortality were age, AF, DBP, log-TG levels and stress hyperglycemia. Stress hyperglycemia does not appear to be directly associated with the outcome of acute ischemic stroke. However, given that patients with stress hyperglycemia had higher prevalence of cardiovascular risk factors than

  7. Rodent models of ischemic stroke lack translational relevance... are baboon models the answer?

    PubMed

    Kwiecien, Timothy D; Sy, Christopher; Ding, Yuchuan

    2014-05-01

    Rodent models of ischemic stroke are associated with many issues and limitations, which greatly diminish the translational potential of these studies. Recent studies demonstrate that significant differences exist between rodent and human ischemic stroke. These differences include the physical characteristics of the stroke, as well as changes in the subsequent inflammatory and molecular pathways following the acute ischemic insult. Non-human primate (NHP) models of ischemic stroke, however, are much more similar to humans. In addition to evident anatomical similarities, the physiological responses that NHPs experience during ischemic stroke are much more applicable to the human condition and thus make it an attractive model for future research. The baboon ischemic stroke model, in particular, has been studied extensively in comparison to other NHP models. Here we discuss the major shortcomings associated with rodent ischemic stroke models and provide a comparative overview of baboon ischemic stroke models. Studies have shown that baboons, although more difficult to obtain and handle, are more representative of ischemic events in humans and may have greater translational potential that can offset these deficiencies. There remain critical issues within these baboon stroke studies that need to be addressed in future investigations. The most critical issue revolves around the size and the variability of baboon ischemic stroke. Compared to rodent models, however, issues such as these can be addressed in future studies. Importantly, baboon models avoid many drawbacks associated with rodent models including vascular variability and inconsistent inflammatory responses - issues that are inherent to the species and cannot be avoided.

  8. Retinal proteomic changes under different ischemic conditions - implication of an epigenetic regulatory mechanism

    PubMed Central

    Stowell, Cheri; Wang, Lin; Arbogast, Brian; Lan, Jing-quan; Cioffi, George A; Burgoyne, Claude F; Zhou, An

    2010-01-01

    In retina, an ischemic injury-resistant condition (ischemic tolerance) can be induced by a sub-lethal ischemic treatment (preconditioning) prior to an otherwise injurious ischemic insult. In this work, we compared retinal proteomic changes under three different ischemic conditions, as a means to identify the effector mechanisms that underlie retinal ischemic tolerance. Transient retinal ischemia was induced by elevating the intraocular pressure (IOP) in three groups of adult rats as follows: Group 1, ischemic-preconditioned, 110 mmHg for 8 minutes followed by 48 hours reperfusion; Group 2, ischemic-injured, 110 mmHg for 60 minutes followed by 24 hours reperfusion; Group 3, ischemic-tolerant, preconditioning treatment followed by another 60 minutes of 110 mmHg and 24 hours reperfusion. Protein quantities in retinas from each of the afore-mentioned retinal ischemic conditions, as determined by quantitative mass spectrometry, were compared with that of the contralateral control eyes (sham-treated). As a result, a total of 328 proteins were identified and quantified; among them, 30–60% of proteins showed a change in abundance under one or more retinal ischemic conditions. In particular, in ischemic-tolerant retinas, histone proteins H2B, H3 and H4 demonstrated an increase in abundance, whereas histone H2A showed a decrease in abundance. Further immunohistochemical analyses confirmed the results of proteomic analyses, and detected an up regulation of tri-methylated histone H3, mono-ubiquitinated histone H2A and Polycomb group protein RING2. Together, these results suggest a role of epigenetic regulation in the induction of retinal ischemic tolerance that involves histone and polycomb proteins. PMID:20740046

  9. TNFR1 mediates increased neuronal membrane EAAT3 expression after in vivo cerebral ischemic preconditioning.

    PubMed

    Pradillo, J M; Hurtado, O; Romera, C; Cárdenas, A; Fernández-Tomé, P; Alonso-Escolano, D; Lorenzo, P; Moro, M A; Lizasoain, I

    2006-01-01

    A short ischemic event (ischemic preconditioning) can result in subsequent resistance to severe ischemic injury (ischemic tolerance). Glutamate is released after ischemia and produces cell death. It has been described that after ischemic preconditioning, the release of glutamate is reduced. We have shown that an in vitro model of ischemic preconditioning produces upregulation of glutamate transporters which mediates brain tolerance. We have now decided to investigate whether ischemic preconditioning-induced glutamate transporter upregulation takes also place in vivo, its cellular localization and the mechanisms by which this upregulation is controlled. A period of 10 min of temporary middle cerebral artery occlusion was used as a model of ischemic preconditioning in rat. EAAT1, EAAT2 and EAAT3 glutamate transporters were found in brain from control animals. Ischemic preconditioning produced an up-regulation of EAAT2 and EAAT3 but not of EAAT1 expression. Ischemic preconditioning-induced increase in EAAT3 expression was reduced by the TNF-alpha converting enzyme inhibitor BB1101. Intracerebral administration of either anti-TNF-alpha antibody or of a TNFR1 antisense oligodeoxynucleotide also inhibited ischemic preconditioning-induced EAAT3 up-regulation. Immunohistochemical studies suggest that, whereas the expression of EAAT3 is located in both neuronal cytoplasm and plasma membrane, ischemic preconditioning-induced up-regulation of EAAT3 is mainly localized at the plasma membrane level. In summary, these results demonstrate that in vivo ischemic preconditioning increases the expression of EAAT2 and EAAT3 glutamate transporters the upregulation of the latter being at least partly mediated by TNF-alpha converting enzyme/TNF-alpha/TNFR1 pathway.

  10. Remote ischemic preconditioning improves post resuscitation cerebral function via overexpressing neuroglobin after cardiac arrest in rats.

    PubMed

    Fan, Ran; Yu, Tao; Lin, Jia-Li; Ren, Guang-Dong; Li, Yi; Liao, Xiao-Xing; Huang, Zi-Tong; Jiang, Chong-Hui

    2016-10-01

    In this study, we investigated the effects of remote ischemic preconditioning on post resuscitation cerebral function in a rat model of cardiac arrest and resuscitation. The animals were randomized into six groups: 1) sham operation, 2) lateral ventricle injection and sham operation, 3) cardiac arrest induced by ventricular fibrillation, 4) lateral ventricle injection and cardiac arrest, 5) remote ischemic preconditioning initiated 90min before induction of ventricular fibrillation, and 6) lateral ventricle injection and remote ischemic preconditioning before cardiac arrest. Reagent of Lateral ventricle injection is neuroglobin antisense oligodeoxynucleotides which initiated 24h before sham operation, cardiac arrest or remote ischemic preconditioning. Remote ischemic preconditioning was induced by four cycles of 5min of limb ischemia, followed by 5min of reperfusion. Ventricular fibrillation was induced by current and lasted for 6min. Defibrillation was attempted after 6min of cardiopulmonary resuscitation. The animals were then monitored for 2h and observed for an additionally maximum 70h. Post resuscitation cerebral function was evaluated by neurologic deficit score at 72h after return of spontaneous circulation. Results showed that remote ischemic preconditioning increased neurologic deficit scores. To investigate the neuroprotective effects of remote ischemic preconditioning, we observed neuronal injury at 48 and 72h after return of spontaneous circulation and found that remote ischemic preconditioning significantly decreased the occurrence of neuronal apoptosis and necrosis. To further comprehend mechanism of neuroprotection induced by remote ischemic preconditioning, we found expression of neuroglobin at 24h after return of spontaneous circulation was enhanced. Furthermore, administration of neuroglobin antisense oligodeoxynucleotides before induction of remote ischemic preconditioning showed that the level of neuroglobin was decreased then partly abrogated

  11. Death and rehospitalization after transient ischemic attack or acute ischemic stroke: one-year outcomes from the adherence evaluation of acute ischemic stroke-longitudinal registry.

    PubMed

    Olson, Daiwai M; Cox, Margueritte; Pan, Wenqin; Sacco, Ralph L; Fonarow, Gregg C; Zorowitz, Richard; Labresh, Kenneth A; Schwamm, Lee H; Williams, Linda; Goldstein, Larry B; Bushnell, Cheryl D; Peterson, Eric D

    2013-10-01

    Longitudinal data directly comparing the rates of death and rehospitalization of patients discharged after transient ischemic attack (TIA) versus acute ischemic stroke (AIS) are lacking. Data were analyzed from 2802 patients (TIA n = 552; AIS n = 2250) admitted to 100 U.S. hospitals participating in the Get With The Guidelines-Stroke and the Adherence Evaluation of Acute Ischemic Stroke-Longitudinal registry. The primary composite outcome was the adjusted rate of all-cause death and rehospitalization over 1 year after discharge. Four additional single or combined outcomes were explored. Compared with AIS, TIA patients were older (median 69 v 66 years; P = .007) and more likely female (53.3% v 44.2%; P < .0001). Secondary prevention medication use after hospital discharge was less intensive after TIA, with underuse for both conditions. All-cause death or rehospitalization at 1 year was similar for TIA and AIS patients (37.7% v 34.6%; P = .271); the frequency for TIA patients was higher after covariate adjustment (hazard ratio [HR] 1.19; 95% confidence interval [CI] 1.01-1.41). One-year all-cause mortality was similar among those with TIA compared to AIS patients (3.8% v 5.7%; P = .071; adjusted HR 0.86; 95% CI 0.52-1.42). All-cause rehospitalizations were higher for TIA compared to AIS patients (36.4% v 33.0%; P = .186; adjusted HR 1.20; 95% CI 1.02-1.42), but similar for stroke rehospitalizations (10.1% v 7.4%; P = .037; adjusted HR 1.38, 95% CI 0.997-1.92). Patients with TIA have similar or worse 12-month postdischarge risk of death or rehospitalization as compared with those with AIS. Outcomes after TIA and AIS might be improved with better adherence to secondary preventive guidelines. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  12. [Multimodal imaging of ischemic heart diseases: A 2015 update].

    PubMed

    Di Marco, L; Rosset, M; Zhang-Yin, J; Ohana, M

    2016-05-01

    Current realities and future possibilities of imaging in the ischemic heart diseases are very broad and constantly evolving, with the improvement of existing technologies and the introduction of new features such as dual-energy CT, strain ultrasound, multimodality fusion or perfusion MRI. Regular collaboration between prescribing clinicians, cardiologists, radiologists and nuclear radiologists is therefore essential to tailor the examination to the specific clinical question. The indications for each modality will therefore depend on its diagnostic performance, cost, acquisition and post-processing times and eventual radiation exposure. This review will detail principles and applications of current cardiac imaging examinations: echocardiography, nuclear medicine, MRI, CT and coronary angiography, emphasizing their current strengths and weaknesses in the ischemic heart diseases management.

  13. Trypanosomiasis, cardiomyopathy and the risk of ischemic stroke.

    PubMed

    Carod-Artal, Francisco Javier

    2010-05-01

    American (Chagas disease) and African (sleeping sickness) trypanosomiasis are neglected tropical diseases and are a heavy burden in Latin America and Africa, respectively. Chagas disease is an independent risk factor for stroke. Apical aneurysm, heart failure and cardiac arrhythmias are associated with ischemic stroke in chagasic cardiomyopathy. Not all chagasic patients who suffer an ischemic stroke have a severe cardiomyopathy, and stroke may be the first manifestation of Chagas disease. Cardioembolism affecting the middle cerebral artery is the most common stroke subtype. Risk of recurrence is high and careful evaluation of recurrence risk should be addressed. Repolarization changes, low voltage and prolonged QT interval are common electrocardiography alterations in human African trypanosomiasis, and can be found in more than 70% of patients. Epidemiological studies are needed to asses the risk of stroke in African trypanosomiasis perimyocarditis.

  14. The Siblings With Ischemic Stroke Study (SWISS): A Progress Report

    PubMed Central

    Meschia, James F.; Kissela, Brett M.; Brott, Thomas G.; Brown, Robert D.; Worrall, Bradford B.; Beck, Jeanne; Skarp, Alexa N.

    2006-01-01

    There is increasing evidence that genetic factors are associated with ischemic stroke, including multiple recent reports of association with the gene PDE4D, encoding phosphodiesterase 4D, on chromosome 5q12. Genetic studies of stroke are important but can be logistically difficult to perform. This article reviews the design of the Siblings With Ischemic Stroke Study (SWISS) and discusses problems in performing a sibling-based pedigree study where proband-initiated consent is used to enroll pedigree members. Proband-initiated enrollment optimizes privacy protections for family members, but it is associated with a substantial pedigree non-completion rate such that 3 to 4 probands must be identified to obtain one completed sibling pedigree. This report updates the progress of enrollment in the SWISS protocol, discusses barriers to pedigree completion and describes innovative approaches used by the SWISS investigators to enhance enrollment. PMID:16595789

  15. Ischemic Colitis Secondary to Ergotamine Use: A Case Study

    PubMed Central

    Rodman, Regina E.; Willson, Thomas D.; Connolly, Mark M.; Podbielski, Francis J.

    2011-01-01

    A 48-year-old woman with a history of chronic migraines, initially admitted for inpatient management of intractable migraine headaches, developed new onset abdominal pain, hypotension, and diarrhea on hospital day number ten. In our institution's headache unit, patients are treated by a multidisciplinary approach, including individualized drug therapy based on diagnosis and previous response to therapy. Given the patient's hypotension and clinical appearance, she was transferred to the intensive care unit and treated for septic shock and metabolic acidosis. A bedside colonscopy revealed diffuse ischemic colitis. Final pathology after colon resection showed widespread, transmural necrosis of the colonic wall. We review the pathophysiology of ergotamine use and its potential association with ischemic colitis. PMID:22347148

  16. Optical-resolution photoacoustic microscopy of ischemic stroke

    NASA Astrophysics Data System (ADS)

    Hu, Song; Gonzales, Ernie; Soetikno, Brian; Gong, Enhao; Yan, Ping; Maslov, Konstantin; Lee, Jin-Moo; Wang, Lihong V.

    2011-03-01

    A major obstacle in understanding the mechanism of ischemic stroke is the lack of a tool to noninvasively or minimally invasively monitor cerebral hemodynamics longitudinally. Here, we applied optical-resolution photoacoustic microscopy (OR-PAM) to longitudinally study ischemic stroke induced brain injury in a mouse model with transient middle cerebral artery occlusion (MCAO). OR-PAM showed that, during MCAO, the average hemoglobin oxygen saturation (sO2) values of feeder arteries and draining veins within the stroke core region dropped ~10% and ~34%, respectively. After reperfusion, arterial sO2 recovered back to the baseline; however, the venous sO2 increased above the baseline value by ~7%. Thereafter, venous sO2 values were close to the arterial sO2 values, suggesting eventual brain tissue infarction.

  17. Blood-brain barrier tight junction permeability and ischemic stroke.

    PubMed

    Sandoval, Karin E; Witt, Ken A

    2008-11-01

    The blood-brain barrier (BBB) is formed by the endothelial cells of cerebral microvessels, providing a dynamic interface between the peripheral circulation and the central nervous system. The tight junctions (TJs) between the endothelial cells serve to restrict blood-borne substances from entering the brain. Under ischemic stroke conditions decreased BBB TJ integrity results in increased paracellular permeability, directly contributing to cerebral vasogenic edema, hemorrhagic transformation, and increased mortality. This loss of TJ integrity occurs in a phasic manner, which is contingent on several interdependent mechanisms (ionic dysregulation, inflammation, oxidative and nitrosative stress, enzymatic activity, and angiogenesis). Understanding the inter-relation of these mechanisms is critical for the development of new therapies. This review focuses on those aspects of ischemic stroke impacting BBB TJ integrity and the principle regulatory pathways, respective to the phases of paracellular permeability.

  18. Nanoparticles-Assisted Stem Cell Therapy for Ischemic Heart Disease.

    PubMed

    Zhu, Kai; Li, Jun; Wang, Yulin; Lai, Hao; Wang, Chunsheng

    2016-01-01

    Stem cell therapy has attracted increasing attention as a promising treatment strategy for cardiac repair in ischemic heart disease. Nanoparticles (NPs), with their superior physical and chemical properties, have been widely utilized to assist stem cell therapy. With the help of NPs, stem cells can be genetically engineered for enhanced paracrine profile. To further understand the fate and behaviors of stem cells in ischemic myocardium, imaging NPs can label stem cells and be tracked in vivo under multiple modalities. Besides that, NPs can also be used to enhance stem cell retention in myocardium. These facts have raised efforts on the development of more intelligent and multifunctional NPs for cellular application. Herein, an overview of the applications of NPs-assisted stem cell therapy is given. Key issues and future prospects are also critically addressed.

  19. Antisense oligonucleotide for tissue factor inhibits hepatic ischemic reperfusion injury.

    PubMed

    Nakamura, Kenji; Kadotani, Yayoi; Ushigome, Hidetaka; Akioka, Kiyokazu; Okamoto, Masahiko; Ohmori, Yoshihiro; Yaoi, Takeshi; Fushiki, Shinji; Yoshimura, Rikio; Yoshimura, Norio

    2002-09-27

    Tissue factor (TF) is an initiation factor for blood coagulation and its expression is induced on endothelial cells during inflammatory or immune responses. We designed an antisense oligodeoxynucleotide (AS-1/TF) for rat TF and studied its effect on hepatic ischemic reperfusion injury. AS-1/TF was delivered intravenously to Lewis rats. After 10 h, hepatic artery and portal vein were partially clamped. Livers were reperfused after 180 min and harvested. TF expression was studied using immunohistochemical staining. One of 10 rats survived in a 5-day survival rate and TF was strongly stained on endothelial cells in non-treatment group. However, by treatment with AS-1/TF, six of seven survived and TF staining was significantly reduced. Furthermore, we observed that fluorescein-labeled AS-1/TF was absorbed into endothelial cells. These results suggest that AS-1/TF can strongly suppress the expression of TF and thereby inhibit ischemic reperfusion injury to the rat liver.

  20. Zoster sine herpete, vertebral artery stenosis, and ischemic stroke.

    PubMed

    Chen, Wei-Hsi; Chui, Chi; Yin, Hsin-Ling

    2013-10-01

    Although a previous or recent history of varicella-zoster virus (VZV) infection is known to increase the risk of stroke in both children and adults, the influence of zoster sine herpetic remains unclear. We report an immunocompetent man with common cold symptoms and conjunctivitis, followed by an acute onset of bulbar weakness and hemihypesthesia without preceding skin rash. Acute medullary infarction and left vertebral artery stenosis were detected. VZV infection was finally identified. Zoster sine herpetic interferes with accurate diagnosis of infectious stroke, and vertebral artery involvement is unusual in ischemic stroke in this situation. An unexplained course of ischemic stroke event should be suspected in patients with VZV cerebrovasculopathy, especially in those without conventional stroke risk factors and those exhibiting concomitant infectious complications. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. Spontaneous sternocleidomastoid muscle hematoma following thrombolysis for acute ischemic stroke.

    PubMed

    Giannantoni, Nadia Mariagrazia; Della Marca, Giacomo; Broccolini, Aldobrando; Pilato, Fabio; Profice, Paolo; Morosetti, Roberta; Caliandro, Pietro; Frisullo, Giovanni

    2014-06-15

    Spontaneous or traumatic bleeding is a common complication of systemic thrombolysis in patients with acute ischemic stroke. We report the case of an 83 y.o. woman with right facio-brachio-crural hemiparesis, left deviation of the head and aphasia who developed, after thrombolytic therapy, a spontaneous sternocleidomastoid muscle hematoma that regressed few days later. To our knowledge, this is the first case reported in the literature of asymptomatic and spontaneous skeletal muscle hematoma following thrombolysis for the treatment of acute ischemic stroke. The occurrence of lateral cervical tuberculosis lymphadenitis ipsilateral to sternocleidomastoid muscle hematoma may suggest a causal relationship between local chronic inflammation of active mycobacterial infection and thrombolysis-related extravasation. This case should suggest caution in thrombolytic treatment in patients with chronic immune dysregulation and vascular inflammation such as extra-pulmonary tuberculosis.

  2. Mechanisms of gender-linked ischemic brain injury

    PubMed Central

    Liu, Mingyue; Dziennis, Suzan; Hurn, Patricia D.; Alkayed, Nabil J.

    2010-01-01

    Biological sex is an important determinant of stroke risk and outcome. Women are protected from cerebrovascular disease relative to men, an observation commonly attributed to the protective effect of female sex hormones, estrogen and progesterone. However, sex differences in brain injury persist well beyond the menopause and can be found in the pediatric population, suggesting that the effects of reproductive steroids may not completely explain sexual dimorphism in stroke. We review recent advances in our understanding of sex steroids (estradiol, progesterone and testosterone) in the context of ischemic cell death and neuroprotection. Understanding the molecular and cell-based mechanisms underlying sex differences in ischemic brain injury will lead to a better understanding of basic mechanisms of brain cell death and is an important step toward designing more effective therapeutic interventions in stroke. PMID:19531872

  3. Neuroprotection in acute ischemic stroke – current status

    PubMed Central

    Auriel, E; Bornstein, NM

    2010-01-01

    Abstract With the growing understanding of the mechanism of cell death in ischemia, new approaches for treatment such as neuroprotection have emerged. The basic aim of this strategy is to interfere with the events of the ischemic cascade, blocking the pathological processes and preventing the death of nerve cells in the ischemic penumebra. This concept involves inhibition of the pathological molecular events which eventually leads to the influx of calcium, activation of free radicals and neuronal death. Despite encouraging data from experimental animal models, all clinical trials of neuroprotective therapies have to date been unsuccessful. This article reviews some of the reasons for the failure of neuroprotection in the clinical trials so far. Despite all the negative reports, we believe it would be wrong to give up at this point, since there is still reasonable hope of finding an effective neuroprotection for stroke. PMID:20716132

  4. Ischemic stroke as the first manifestation of hepatic epithelioid hemangioendothelioma.

    PubMed

    Zis, Panagiotis; Assi, Avraam; Kravaritis, Dimitrios; Sevastianos, Vassilios A

    2014-03-01

    A 38-year-old obese woman, with a past medical history of cholecystectomy and dyslipidaemia, presented with acute occipital headache, vomiting and rotational vertigo which lasted 8 hours. On admission neurological examination was unremarkable, however general physical examination revealed hepatomegaly. Routine blood tests showed abnormal liver function tests. MRI scan indicated an acute ischemic infarct in the right cerebellum. Extensive investigation was negative. However, liver MRI revealed multiple lesions in both liver lobes. Ultrasound guided liver biopsy and histopathological analysis confirmed the diagnosis of hepatic hemangioendothelioma. In conclusion, hypercoaguable state related to hepatic epithelioid hemangioendothelioma can lead to an ischemic stroke, as a rare first manifestation of the disease. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. Amelioration of ischemic brain damage by peritoneal dialysis

    PubMed Central

    Godino, María del Carmen; Romera, Victor G.; Sánchez-Tomero, José Antonio; Pacheco, Jesus; Canals, Santiago; Lerma, Juan; Vivancos, José; Moro, María Angeles; Torres, Magdalena; Lizasoain, Ignacio; Sánchez-Prieto, José

    2013-01-01

    Ischemic stroke is a devastating condition, for which there is still no effective therapy. Acute ischemic stroke is associated with high concentrations of glutamate in the blood and interstitial brain fluid. The inability of the tissue to retain glutamate within the cells of the brain ultimately provokes neuronal death. Increased concentrations of interstitial glutamate exert further excitotoxic effects on healthy tissue surrounding the infarct zone. We developed a strategy based on peritoneal dialysis to reduce blood glutamate levels, thereby accelerating brain-to-blood glutamate clearance. In a rat model of stroke, this simple procedure reduced the transient increase in glutamate, consequently decreasing the size of the infarct area. Functional magnetic resonance imaging demonstrated that the rescued brain tissue remained functional. Moreover, in patients with kidney failure, peritoneal dialysis significantly decreased glutamate concentrations. Our results suggest that peritoneal dialysis may represent a simple and effective intervention for human stroke patients. PMID:23999426

  6. Interactions between Age, Sex, and Hormones in Experimental Ischemic Stroke

    PubMed Central

    Liu, Fudong; McCullough, Louise D.

    2012-01-01

    Age, sex, and gonadal hormones have profound effects on ischemic stroke outcomes, although how these factors impact basic stroke pathophysiology remains unclear. There is a plethora of inconsistent data reported throughout the literature, primarily due to differences in the species examined, the timing and methods used to evaluate injury, the models used, and confusion regarding differences in stroke incidence as seen in clinical populations versus effects on acute neuroprotection or neurorepair in experimental stroke models. Sex and gonadal hormone exposure have considerable independent impact on stroke outcome, but these factors also interact with each other, and the contribution of each differs throughout the lifespan. The contribution of sex and hormones to experimental stroke will be the focus of this review. Recent advances and our current understanding of age, sex, and hormone interactions in ischemic stroke with a focus on inflammation will be discussed. PMID:23068990

  7. [Segmental ischemic lesions of the mesenteric small intestine].

    PubMed

    Maurano, A; Cirillo, L C; de Lutio di Castelguidone, E; Fondacaro, R

    1987-01-01

    Segmental ischemic disease consists of segmental infarctions and ischemic stenoses. Vasculitis (LES, polyarteritis nodosa, Schönlein-Henoch syndrome), thrombosis, arteriosclerotic changes, mechanical obstructions (adhesions, hernia, volvulus, traumas), hemorrhagic disorders are the most common causes of these intestinal lesions. The authors report their experience achieved during three years on 428 small bowel examinations; among these, 197 were double contrast enemas. Ten patients showed roentgenographic features referred to vascular diseases: 1 LES, 1 Schönlein-Henoch syndrome, 3 polyarteritis nodosa, 5 spontaneous hemorrhagic disorders or due to treatment with anticoagulants. The authors, after a review of the radiological findings, emphasize the high sensitivity and low specificity of double contrast small bowel enema. Furthermore they underline the usefulness of this method in demonstrating and monitoring intestinal pathologic changes.

  8. Investigation of reperfusion injury and ischemic preconditioning in microsurgery.

    PubMed

    Wang, Wei Zhong

    2009-01-01

    Ischemia/reperfusion (I/R) is inevitable in many vascular and musculoskeletal traumas, diseases, free tissue transfers, and during time-consuming reconstructive surgeries in the extremities. Salvage of a prolonged ischemic extremity or flap still remains a challenge for the microvascular surgeon. One of the common complications after microsurgery is I/R-induced tissue death or I/R injury. Twenty years after the discovery, ischemic preconditioning has emerged as a powerful method for attenuating I/R injury in a variety of organs or tissues. However, its therapeutic expectations still need to be fulfilled. In this article, the author reviews some important experimental evidences of I/R injury and preconditioning-induced protection in the fields relevant to microsurgery.

  9. Endovascular reperfusion therapies for acute ischemic stroke: dissecting the evidence.

    PubMed

    Tsivgoulis, Georgios; Safouris, Apostolos; Krogias, Christos; Arthur, Adam S; Alexandrov, Andrei V

    2016-05-01

    Ischemic stroke is a major cause of death and disability and intravenous thrombolysis has been the only approved acute reperfusion therapy (RT) for many years. Seven randomized-controlled clinical trials (RCTs) evaluating the safety and efficacy of endovascular therapy in patients with acute ischemic stroke (AIS) due to emergent large vessel occlusion (ELVO) have been recently published. These studies have changed the treatment paradigm by establishing mechanical thrombectomy (MT) as the most effective acute stroke therapy for improving functional outcome in anterior circulation ELVO with a NNT of 6. The present review will critically evaluate the results of these RCTs and of the existing meta-analyses investigating the safety and efficacy of endovascular therapy for AIS. Points of debate such as acute stroke imaging, posterior circulation stroke and general anesthesia will be addressed. We will also discuss health policies aiming to increase the availability of endovascular treatment for stroke patients.

  10. Endocardial substrate mapping for monomorphic ventricular tachycardia ablation in ischemic and non-ischemic cardiomyopathy.

    PubMed

    Fukuzawa, Koji; Yoshida, Akihiro; Kubo, Shinya; Takano, Takatsugu; Kiuchi, Kunihiko; Kanda, Gaku; Takami, Kaoru; Kumagai, Hiroyuki; Torii, Satoko; Takami, Mitsuru; Yokoyama, Mitsuhiro; Hirata, Ken-ichi

    2008-07-18

    We investigated the differences in the endocardial substrates between ischemic cardiomyopathy (ICM) and non-ICM (NICM) by using electro-anatomical mapping and pace-mapping. We studied 18 patients (ICM and NICM, 9 each) with monomorphic ventricular tachycardia (VT) documented by 12-leads ECG. Low voltage area was defined by signal amplitude <1.5 mV. A pace-map QRS morphology that matched VT in >10 of the 12-leads ECG was regarded as a pace-map match. And conduction delay during pace-mapping was defined as the stimulus to QRS interval >or=40 ms. Low voltage area was 53.8 +/- 21.5 and 20.8 +/- 16.7 cm2 in ICM and NICM patients, respectively (P = 0.002). Pace-mapping was assessed in 6 ICM and 9 NICM. Pace-map match with conduction delay were obtained in all the 6 ICM patients. But in NICM patients, pace-map match with conduction delay was obtained in 3 patients. Pace-map match sites where conduction delay was not observed were obtained in 5 patients. Pace-map match could not be obtained in 1 patient. We attempted ablation in 6 ICM and 7 NICM patients. Subsequently, VT recurrence was not observed in ICM but it was observed in 6 of 7 NICM patients (log-rank P = 0.0016). In NICM patients, the arrhythmogenic substrate that represented the abnormal electrogram and conduction delay was observed less within the endocardial surface when compared with that observed in ICM. VT recurrence rate subsequent to endocardial ablation was higher in NICM than in ICM patients.

  11. Tat-glyoxalase protein inhibits against ischemic neuronal cell damage and ameliorates ischemic injury.

    PubMed

    Shin, Min Jea; Kim, Dae Won; Lee, Yeom Pyo; Ahn, Eun Hee; Jo, Hyo Sang; Kim, Duk-Soo; Kwon, Oh-Shin; Kang, Tae-Cheon; Cho, Yong-Jun; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2014-02-01

    Methylglyoxal (MG), a metabolite of glucose, is the major precursor of protein glycation and induces apoptosis. MG is associated with neurodegeneration, including oxidative stress and impaired glucose metabolism, and is efficiently metabolized to S-D-lactoylglutathione by glyoxalase (GLO). Although GLO has been implicated as being crucial in various diseases including ischemia, its detailed functions remain unclear. Therefore, we investigated the protective effect of GLO (GLO1 and GLO2) in neuronal cells and an animal ischemia model using Tat-GLO proteins. Purified Tat-GLO protein efficiently transduced into HT-22 neuronal cells and protected cells against MG- and H2O2-induced cell death, DNA fragmentation, and activation of caspase-3 and mitogen-activated protein kinase. In addition, transduced Tat-GLO protein increased D-lactate in MG- and H2O2-treated cells whereas glycation end products (AGE) and MG levels were significantly reduced in the same cells. Gerbils treated with Tat-GLO proteins displayed delayed neuronal cell death in the CA1 region of the hippocampus compared with a control. Furthermore, the combined neuroprotective effects of Tat-GLO1 and Tat-GLO2 proteins against ischemic damage were significantly higher than those of each individual protein. Those results demonstrate that transduced Tat-GLO protein protects neuronal cells by inhibiting MG- and H2O2-mediated cytotoxicity in vitro and in vivo. Therefore, we suggest that Tat-GLO proteins could be useful as a therapeutic agent for various human diseases related to oxidative stress including brain diseases. © 2013 Elsevier Inc. All rights reserved.

  12. Prevalence of positive diffusion-weighted imaging findings and ischemic stroke recurrence in transient ischemic attack.

    PubMed

    Gon, Yasufumi; Sakaguchi, Manabu; Okazaki, Shuhei; Mochizuki, Hideki; Kitagawa, Kazuo

    2015-05-01

    The relationship between transient ischemic attack (TIA) clinical etiology, positive diffusion-weighted imaging (DWI) findings, and stroke recurrence is controversial. This study aimed to clarify the prevalence of positive DWI findings and TIA recurrence in relation to TIA patient characteristics. The subjects were patients admitted to our stroke unit within 7 days after symptom onset between January 2006 and July 2013. We examined DWI findings and TIA recurrence according to etiologic subtypes. We enrolled 139 patients with lacunar TIA (n = 17), atherothrombotic TIA (n = 35), cardioembolic TIA (n = 25), TIA due to other causes (n = 32), or TIA with undetermined etiology (n = 30). The prevalence of positive DWI findings was highest among the cardioembolic TIA patients (56.0%). No association was found between the prevalence of positive DWI findings and symptom duration, motor presence, or ABCD(2) score. Plasma d-dimer level was significantly higher in the DWI-positive group than that in the DWI-negative group (P = .01). The prevalence of TIA recurrence was highest (5 of 35, 14.3%) among the atherothrombotic TIA patients, regardless of positive DWI findings. None of the patients treated with the anticoagulant and antiplatelet combination therapy experienced a recurrence. In contrast, almost all patients with cardioembolic TIA received anticoagulant treatment and none experienced recurrence. The prevalence of positive DWI findings was high among the cardiogenic TIA patients. TIA recurrence was often observed among the atherothrombotic TIA patients treated with antiplatelets. Management of patients with atherothrombotic TIA requires further aggressive antithrombotic strategy. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  13. Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

    PubMed Central

    Legrand, Matthieu; Mik, Egbert G; Johannes, Tanja; Payen, Didier; Ince, Can

    2008-01-01

    Ischemia is the most common cause of acute renal failure. Ischemic-induced renal tissue hypoxia is thought to be a major component in the development of acute renal failure in promoting the initial tubular damage. Renal oxygenation originates from a balance between oxygen supply and consumption. Recent investigations have provided new insights into alterations in oxygenation pathways in the ischemic kidney. These findings have identified a central role of microvascular dysfunction related to an imbalance between vasoconstrictors and vasodilators, endothelial damage and endothelium–leukocyte interactions, leading to decreased renal oxygen supply. Reduced microcirculatory oxygen supply may be associated with altered cellular oxygen consumption (dysoxia), because of mitochondrial dysfunction and activity of alternative oxygen-consuming pathways. Alterations in oxygen utilization and/or supply might therefore contribute to the occurrence of organ dysfunction. This view places oxygen pathways’ alterations as a potential central player in the pathogenesis of acute kidney injury. Both in regulation of oxygen supply and consumption, nitric oxide seems to play a pivotal role. Furthermore, recent studies suggest that, following acute ischemic renal injury, persistent tissue hypoxia contributes to the development of chronic renal dysfunction. Adaptative mechanisms to renal hypoxia may be ineffective in more severe cases and lead to the development of chronic renal failure following ischemia-reperfusion. This paper is aimed at reviewing the current insights into oxygen transport pathways, from oxygen supply to oxygen consumption in the kidney and from the adaptation mechanisms to renal hypoxia. Their role in the development of ischemia-induced renal damage and ischemic acute renal failure are discussed. PMID:18488066

  14. VEGF expression in human brain tissue after acute ischemic stroke.

    PubMed

    Mărgăritescu, Otilia; Pirici, D; Mărgăritescu, Cl

    2011-01-01

    Ischemic stroke is the third most common cause of death in humans, requiring further studies to elucidate its pathophysiological background. One potential mechanism to increase oxygen delivery to the affected tissue is induction of angiogenesis. The most potent proangiogenic factor is VEGF. For this reason, our study investigated immunohistochemically VEGF reactivity in different cellular brain compartments from 15 ischemic stroke patients, as well as from 2 age control cases. By enzymatic immunohistochemistry, we investigate VEGF expression in different brain cell compartments and then we quantified its signal intensity by assessing integrated optical densities (IOD). To establish the exact cellular brain topography of VEGF immunoreactivity we performed double fluorescent immunohistochemistry series (VEGF÷NeuN, GFAP, CD68, CD105). In control samples, VEGF reactivity was observed especially in neurons from the Brodmann cortical layers IV to VI and in protoplasmic astrocytes from the deeper layers of gray matter and in endothelial cells from normal blood vessels because of systemic hypoxia generated after death. In acute ischemic stroke samples, this reactivity was noticed in all brain cellular compartments but with different intensities. The most reactive compartment was the neurons, the intensity of VEGF reaction decreasing with the lesional age from the core infarct toward intact adjacent brain cortex. With a lower intensity, VEGF reaction was noticed in astrocytes compartments, especially in gemistocytic astrocytes adjacent to the liquefaction zone. We also noticed a weak reaction in activated non-phagocytic microglia from the periphery of liquefaction zones, and high VEGF-CD105 colocalization values at the level of microvessels that surround the infarcted brain area. In conclusion, this reactivity could suggest that VEGF might exhibit neuronal and glial protective effects and also a neoangiogenic property in acute ischemic stroke, facts that may have

  15. Amphetamine-related ischemic colitis causing gastrointestinal bleeding

    PubMed Central

    Panikkath, Deepa

    2016-01-01

    A 43-year-old woman presented with acute lower intestinal bleeding requiring blood transfusion. Multiple initial investigations did not reveal the cause of the bleeding. Colonoscopy performed 2 days later showed features suggestive of ischemic colitis. On detailed history, the patient admitted to using amphetamines, and her urine drug screen was positive for them. She was managed conservatively and advised not to use amphetamines again. She did not have any recurrence on 2-year follow-up. PMID:27365888

  16. Lipid Profile Components and Risk of Ischemic Stroke

    PubMed Central

    Willey, Joshua Z.; Xu, Qiang; Boden-Albala, Bernadette; Paik, Myunghee C.; Moon, Yeseon Park; Sacco, Ralph L.; Elkind, Mitchell S. V.

    2010-01-01

    Objective To explore the relationship between lipid profile components and incident ischemic stroke in a stroke-free prospective cohort. Design Population-based prospective cohort study. Setting Northern Manhattan, New York. Patients Stroke-free community residents. Intervention As part of the Northern Manhattan Study, baseline fasting blood samples were collected on stroke-free community residents followed up for a mean of 7.5 years. Main Outcome Measures Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for lipid profile components and ischemic stroke after adjusting for demographic and risk factors. In secondary analyses, we used repeated lipid measures over 5 years from a 10% sample of the population to calculate the change per year of each of the lipid parameters and to impute time-dependent lipid parameters for the full cohort. Results After excluding those with a history of myocardial infarction, 2940 participants were available for analysis. Baseline high-density lipoprotein cholesterol, triglyceride, and total cholesterol levels were not associated with risk of ischemic stroke. Low-density lipoprotein cholesterol (LDL-C) and non–high-density lipoprotein cholesterol levels were associated with a paradoxical reduction in risk of stroke. There was an interaction with use of cholesterol-lowering medication on follow-up, such that LDL-C level was only associated with a reduction in stroke risk among those taking medications. An LDL-C level greater than 130 mg/dL as a time-dependent covariate showed an increased risk of ischemic stroke (adjusted hazard ratio, 3.81; 95% confidence interval, 1.53–9.51). Conclusions Baseline lipid panel components were not associated with an increased stroke risk in this cohort. Treatment with cholesterol-lowering medications and changes in LDL-C level over time may have attenuated the risk in this population, and lipid measurements at several points may be a better marker of

  17. [Uncaria tomentosa and acute ischemic kidney injury in rats].

    PubMed

    de Fátima Fernandes Vattimo, Maria; da Silva, Natalia Oliveira

    2011-03-01

    The objective of this study was to evaluate the renoprotective effects of Uncaria Tomentosa (cat's claw) on ischemic acute kidney injury induced by renal clamping in rats. The hypoxia and hypoperfusion increase the production of reactive species already present in the inflammatory process. Results showed that the renal function evaluated by creatinine clearance, the urinary excretion of peroxides and malondealdehyde indexes demonstrated that UT induced renoprotection, probably related to its antioxidant activities.

  18. "Cat scratch colon" in a patient with ischemic colitis.

    PubMed

    Park, Eui Ju; Lee, Joon Seong; Lee, Tae Hee; Choi, Dae Han; Kim, Eui Bae; Jeon, Seong Ran; Hong, Su Jin; Kim, Jin-Oh

    2015-03-01

    "Cat scratch colon" is a gross finding characterized by hemorrhagic mucosal scratches on colonoscopy. It is usually associated with a normal colon and is rarely associated with collagenous colitis. In a previous report, cat scratch colon was noted in the cecum and ascending colon, but has also been observed in the distal transverse colon. The patient in this study was also diagnosed with ischemic colitis that may have played a role in the development of cat scratch colon.

  19. "Cat Scratch Colon" in a Patient with Ischemic Colitis

    PubMed Central

    Park, Eui Ju; Lee, Tae Hee; Choi, Dae Han; Kim, Eui Bae; Jeon, Seong Ran; Hong, Su Jin; Kim, Jin-Oh

    2015-01-01

    "Cat scratch colon" is a gross finding characterized by hemorrhagic mucosal scratches on colonoscopy. It is usually associated with a normal colon and is rarely associated with collagenous colitis. In a previous report, cat scratch colon was noted in the cecum and ascending colon, but has also been observed in the distal transverse colon. The patient in this study was also diagnosed with ischemic colitis that may have played a role in the development of cat scratch colon. PMID:25844349

  20. Loss of the Mexican American survival advantage after ischemic stroke

    PubMed Central

    Morgenstern, Lewis B.; Brown, Devin L.; Smith, Melinda A.; Sánchez, Brisa N.; Zahuranec, Darin B.; Garcia, Nelda; Kerber, Kevin A.; Skolarus, Lesli E.; Meurer, William J; Burke, James F; Adelman, Eric E.; Baek, Jonggyu; Lisabeth, Lynda D.

    2014-01-01

    Background and Purpose Mexican Americans (MAs) were previously found to have lower mortality following ischemic stroke than non Hispanic Whites (NHWs). We studied mortality trends in a population-based design. Methods Active and passive surveillance were used to find all ischemic stroke cases from January, 2000–December, 2011 in Nueces County, Texas. Deaths were ascertained from the Texas Department of Health through December 31 2012. Cumulative 30-day and 1 year mortality adjusted for covariates was estimated using log-binomial models with a linear term for year of stroke onset used to model time trends. Models used data from the entire study period to estimate adjusted mortality among stroke cases in 2000 and 2011, and to calculate projected ethnic differences. Results There were 1,974 ischemic strokes among NHWs and 2,439 among MAs. Between 2000 and 2011, model estimated mortality declined among NHWs at 30 days (7.6% to 5.6%, p=0.24) and 1 year (20.8% to 15.5%, p=0.02). Among MAs, 30-day model estimated mortality remained stagnant at 5.1% to 5.2% (p=0.92), and a slight decline from 17.4% to 15.3% was observed for 1 year mortality (p=0.26). While ethnic differences in 30-day (p=0.01) and 1 year (p=0.06) mortality were apparent in 2000, they were not so in 2011 (30-day, p=0.63; 1 year p=0.92). Conclusions Overall, mortality following ischemic stroke has declined in the last decade, although significant declines were only observed for NHWs and not MAs at 1 year. The survival advantage previously documented among MAs vanished by 2011. Renewed stroke prevention and treatment efforts for MAs are needed. PMID:25074514

  1. Compromised Wound Healing in Ischemic Type 2 Diabetic Rats

    PubMed Central

    Yu, Tianyi; Chang, Qingxuan; Wang, Di; Gao, Min; Zhang, Xiong; Liu, Yan

    2016-01-01

    Ischemia is one of the main epidemic factors and characteristics of diabetic chronic wounds, and exerts a profound effect on wound healing. To explore the mechanism of and the cure for diabetic impaired wound healing, we established a type 2 diabetic rat model. We used an 8weeks high fat diet (HFD) feeding regimen followed by multiple injections of streptozotocin (STZ) at a dose of 10mg/kg to induce Wister rat to develop type 2 diabetes. Metabolic characteristics were assessed at the 5th week after the STZ injections to confirm the establishment of diabetes mellitus on the rodent model. A bipedicle flap, with length to width ratio 1.5, was performed on the back of the rat to make the flap area ischemic. Closure of excisional wounds on this bipedicle flap and related physiological and pathological changes were studied using histological, immunohistochemical, real time PCR and protein immunoblot approaches. Our results demonstrated that a combination of HFD feeding and a low dose of STZ is capable of inducing the rats to develop type 2 diabetes with noticeable insulin resistance, persistent hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol and high triglyceride levels. The excision wounds on the ischemic double pedicle flap showed deteriorative healing features comparing with non-ischemic diabetic wounds, including: delayed healing, exorbitant wound inflammatory response, excessive and prolonged ROS production and excessive production of MMPs. Our study suggested that HFD feeding combined with STZ injection could induce type 2 diabetes in rat. Our ischemic diabetic wound model is suitable for the investigation of human diabetic related wound repair; especically for diabetic chronic wounds. PMID:27028201

  2. Association of serum uric acid with ischemic stroke.

    PubMed

    Khalil, M I; Islam, M J; Ullah, M A; Khan, R K; Munira, S; Haque, M A; Mamun, M A; Islam, M T; Khan, M H

    2013-04-01

    The present study has examined the association between ischemic stroke and hyperuricemia in Bangladeshi population. This age and sex matched case control study was carried out in the Department of Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh during the period of January 2007 to December 2008. A total of 120 subjects were included in this study, among them 60 were cases and another 60 were controls. Data were collected purposively. Multiple logistic regressions were done to identify the risk factors for ischemic stroke. In this study 68.3% were male and 31.7% were female in both the groups. Male and female ratio of stroke patients was 2.16:1. Mean±SD of serum uric acid level of case and control group was 4.94±1.76 and 3.72±1.09 respectively. Among the case group 76.7% had normal and 23.3% had abnormal serum uric acid level. On the other hand, 93.3% respondents of control group had normal and 6.7% had abnormal serum uric acid (SUA) level. Significant differences was found between case and control group in term of SUA level (p<0.05). Since SUA level is a quantitative numerical variable, an increase in 1mg/dl has a 47.0% (95% CI 1.0% to 2.16%) increase in odds ratio (OR) of having ischemic stroke. This 47.0% is obtained by taking OR for uric acid-1. Elevated serum uric acid level is not significant for ischemic stroke among the Bangladeshi population.

  3. Neonatal parechovirus leucoencephalitis- radiological pattern mimicking hypoxic-ischemic encephalopathy.

    PubMed

    Amarnath, C; Helen Mary, T; Periakarupan, A; Gopinathan, K; Philson, J

    2016-02-01

    Our objective is to study the MR imaging pattern in neonatal parechoviral leucoencephalitis, a rare cause of neonatal white matter abnormality and to differentiate it from hypoxic-ischemic encephalopathy which is the commonest cause of white matter change in neonates. We evaluated 25 neonates who presented with features of encephalopathy. Cranial ultrasound and MR imaging was done in all the cases. The pattern of white matter abnormality was analyzed in all cases. Neonatal leucoencephalitis caused by HPeV has a distinctive clinical presentation and has predilection for the white matter, causing diffusion restricting signal intensity changes involving the periventricular and subcortical white matter, in particular the frontal white matter, also the corpus callosum, internal capsule, external capsule and pyramidal tracts of the supratentorial brain and cerebral peduncle with relative sparing of occipital white matter, thalamus, basal ganglia and the infratentorial regions. Follow up imaging shows disappearance of the lesion without white matter loss. Whereas mild to moderate hypoxic-ischemic injury in a full-term neonate causes lesions in the watershed areas, and subcortical white matter predominantly involving the parietooccipital region and perirolandic region. Thalamus, brainstem, cerebellum, and deep gray matter structures are involved depending on the severity. White matter changes in the neonatal period are commonly associated with hypoxic-ischemic injuries and metabolic causes, less frequently, infection like parechovirus leucoencephalitis. HPeV infection must be considered in infants with specific pattern of white matter change but no convincing history of a perinatal hypoxic-ischemic insult, thus differentiating it from HIE. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. MRI patterns of global hypoxic-ischemic injury in adults.

    PubMed

    Muttikkal, Thomas J Eluvathingal; Wintermark, Max

    2013-07-01

    To assess MRI patterns and associated clinical outcome in adults with global hypoxic-ischemic injury. In order to identify the patients with evidence of global hypoxic-ischemic injury, we retrospectively searched our radiology information system for reports of brain MRI studies from 01/01/2004 to 12/31/2010, containing the keywords - "hypoxia", "hypoxic", "anoxia" and "anoxic". A board certified neuroradiologist visually inspected the corresponding MR images for the presence, location and extent (focal versus diffuse) of ischemic findings. Clinical data for these patients was collected from the electronic medical records, including mechanism of the hypoxic-ischemic injury, and clinical outcome was measured using modified Rankin Scale (mRS). Review of radiology reports identified 151 cases, of which 64 patients remained after exclusion of normal studies ("no hypoxia" in the report), pediatric patients and patients with remote perinatal hypoxia. Five patients had relatively favorable clinical outcome (mRS of 1 to 3) and 59 had poor outcome (mRS of 4 to 6). Patterns associated with relatively favorable clinical outcome were: a) watershed pattern and b) basal ganglia without cortical involvement. Patterns associated with poor clinical outcome were: a) diffuse cortical and deep grey matter pattern, with and without perirolandic sparing; (b) medial occipital with perirolandic involvement; c) precentral gyrus involvement; d) diffuse white matter involvement; e) brainstem involvement; f) cerebellar involvement and g) hippocampal involvement. The vast majority of patients with MRI patterns of hypoxic-anoxic injury have a poor clinical outcome, independently of the observed pattern, with the only relative exception being the watershed pattern and the basal ganglia pattern without cortical involvement. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  5. Ischemic Stroke in the Elderly: Septuagenarians Versus Octogenarians

    PubMed Central

    BAŞTAN, Birgül; GÜNAYDIN, Sefer; BALCI, Fatma Belgin; ACAR, Hürtan; MUTLU, Aytül; ÖZER, Feriha; ÇOKAR, Özlem

    2016-01-01

    Introduction Stroke prevalence is known to increase with age. Approximately 50% of acute ischemic stroke patients are aged between 70 and 89 years. Methods In this study, records of 770 ischemic stroke patients who were 70–89 years old were retrospectively examined (407 septuagenarians and 363 octogenarians). The demographics, comorbid conditions, ischemic stroke type, and stroke outcome for the two age groups were analyzed. Results Comorbid hypertension, diabetes mellitus, and HbA1c levels of ≥6.5% more frequently occurred in septuagenarians than in octogenarians (80.6% versus 70.8%, p=0.002; 32.2% versus 21.8%, p=0.001; and 35% versus 23.2%, p=0.003, respectively), whereas atrial fibrillation was significantly higher in octogenarians (49.3% versus 41.5%, p=0.03). Hypercholesterolemia, previous stroke history, and antiaggregant and/or anticoagulant use were not significantly different between the two age groups. Based on the Oxfordshire Community Stroke Project classification, the most common stroke subtype in the septuagenarian group was a lacunar infarction and in the octogenarian group, it was a partial anterior circulation infarct. According to the Modified Ranking Score, the number of patients living independently was higher for septuagenarians (42.8% versus 27.8%, p<0.001). Conclusion The present findings indicate that the clinical characteristics of ischemic stroke differed between septuagenarians and octogenarians. Therefore, elderly stroke patients cannot be accepted as a homogeneous group. Because this is a hospital-based study, our findings need to be tested via additional epidemiological studies. PMID:28360808

  6. Dysplasia-like epithelial atypia in ischemic bowel disease.

    PubMed

    Abraham, Susan C; Taggart, Melissa W; Loftus, Edward V; Wu, Tsung-Teh

    2014-07-01

    Inflammatory and reactive conditions are known to mimic dysplasia or malignancy in the gastrointestinal tract. Epithelial atypia that closely mimics low-grade dysplasia (LGD) or high-grade dysplasia (HGD) can sometimes be seen in ischemic bowel. To study this phenomenon, we evaluated surgical resections for ischemic enteritis (n = 65) and ischemic colitis (n = 99) that included sections of viable epithelium adjacent to necrosis. Viable epithelium was classified as normal, obviously reactive, LGD-like atypia or high-grade dysplasia (HGD)-like atypia. Cases with available paraffin blocks were characterized immunohistochemically with antibodies to p16, p53, and MIB-1. Fourteen dysplastic lesions in chronic ulcerative colitis served as controls. Dysplasia-like atypia was found in 13 small bowel resections (20%) and 15 colectomies (15%), most common near re-epithelializing erosions. Two colectomies had extensive dysplasia-like atypia, whereas the other 26 demonstrated focal or several foci of atypia. Nine cases contained HGD-like atypia, 15 contained LGD-like atypia, and 4 showed both HGD- and LGD-like atypia. Features indicating subacute-to-chronic ischemia were more frequent in LGD-like atypia (13/15, 87%) than HGD-like atypia (2/9, 22%; P = .003). Dysplasia-like atypia showed overexpression of p16 (73%), p53 (50%), and MIB-1 (92%), but these markers did not reliably distinguish dysplasia-like atypia from true dysplasia in chronic ulcerative colitis (P = .45 for p16, P = .51 for p53, P = .08 for MIB-1). These results underscore the frequency of dysplasia-like atypia in ischemic bowel, which can occasionally be an extensive and worrisome finding. Distinction from true dysplasia requires recognizing the context of the epithelial atypia because cell cycle markers were not helpful in classifying individual cases. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Classifiers for Ischemic Stroke Lesion Segmentation: A Comparison Study

    PubMed Central

    Maier, Oskar; Schröder, Christoph; Forkert, Nils Daniel; Martinetz, Thomas; Handels, Heinz

    2015-01-01

    Motivation Ischemic stroke, triggered by an obstruction in the cerebral blood supply, leads to infarction of the affected brain tissue. An accurate and reproducible automatic segmentation is of high interest, since the lesion volume is an important end-point for clinical trials. However, various factors, such as the high variance in lesion shape, location and appearance, render it a difficult task. Methods In this article, nine classification methods (e.g. Generalized Linear Models, Random Decision Forests and Convolutional Neural Networks) are evaluated and compared with each other using 37 multiparametric MRI datasets of ischemic stroke patients in the sub-acute phase in terms of their accuracy and reliability for ischemic stroke lesion segmentation. Within this context, a multi-spectral classification approach is compared against mono-spectral classification performance using only FLAIR MRI datasets and two sets of expert segmentations are used for inter-observer agreement evaluation. Results and Conclusion The results of this study reveal that high-level machine learning methods lead to significantly better segmentation results compared to the rather simple classification methods, pointing towards a difficult non-linear problem. The overall best segmentation results were achieved by a Random Decision Forest and a Convolutional Neural Networks classification approach, even outperforming all previously published results. However, none of the methods tested in this work are capable of achieving results in the range of the human observer agreement and the automatic ischemic stroke lesion segmentation remains a complicated problem that needs to be explored in more detail to improve the segmentation results. PMID:26672989

  8. Inflammation and glial responses in ischemic brain lesions.

    PubMed

    Stoll, G; Jander, S; Schroeter, M

    1998-10-01

    Focal cerebral ischemia elicits a strong inflammatory response involving early recruitment of granulocytes and delayed infiltration of ischemic areas and the boundary zones by T cells and macrophages. Infiltration of hematogenous leukocytes is facilitated by an upregulation of the cellular adhesion molecules P-selectin, intercellular adhesion molecule-1 and vascular adhesion molecule-1 on endothelial cells. Blocking of the leukocyte/endothelial cell adhesion process significantly reduces stroke volume after transient, but not permanent middle cerebral artery occlusion. In the infarct region microglia are activated within hours and within days transform into phagocytes. Astrocytes upregulate intermediate filaments, synthesize neurotrophins and form glial scars. Local microglia and infiltrating macrophages demarcate infarcts and rapidly remove debris. Remote from the lesion no cellular infiltration occurs, but astroglia and microglia are transiently activated. Astrocytic activation is induced by spreading depression. In focal ischemia neurons die acutely by necrosis and in a delayed fashion by programmed cell death, apoptosis. Proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 beta are upregulated within hours in ischemic brain lesions. Either directly or via induction of neurotoxic mediators such as nitric oxide, cytokines may contribute to infarct progression in the post-ischemic period. On the other hand, inflammation is tightly linked with rapid removal of debris and repair processes. At present it is unclear whether detrimental effects of inflammation outweigh neuroprotective mechanisms or vice versa. In global ischemia inflammatory responses are limited, but micro- and astroglia are also strongly activated. Glial responses significantly differ between brain regions with selective neuronal death and neighbouring areas that are more resistent to ischemic damage.

  9. Predictors and Outcomes of Dysphagia Screening After Acute Ischemic Stroke.

    PubMed

    Joundi, Raed A; Martino, Rosemary; Saposnik, Gustavo; Giannakeas, Vasily; Fang, Jiming; Kapral, Moira K

    2017-04-01

    Guidelines advocate screening all acute stroke patients for dysphagia. However, limited data are available regarding how many and which patients are screened and how failing a swallowing screen affects patient outcomes. We sought to evaluate predictors of receiving dysphagia screening after acute ischemic stroke and outcomes after failing a screening test. We used the Ontario Stroke Registry from April 1, 2010, to March 31, 2013, to identify patients hospitalized with acute ischemic stroke and determine predictors of documented dysphagia screening and outcomes after failing the screening test, including pneumonia, disability, and death. Among 7171 patients, 6677 patients were eligible to receive dysphagia screening within 72 hours, yet 1280 (19.2%) patients did not undergo documented screening. Patients with mild strokes were significantly less likely than those with more severe strokes to have documented screening (adjusted odds ratio, 0.51; 95% confidence interval [CI], 0.41-0.64). Failing dysphagia screening was associated with poor outcomes, including pneumonia (adjusted odds ratio, 4.71; 95% CI, 3.43-6.47), severe disability (adjusted odds ratio, 5.19; 95% CI, 4.48-6.02), discharge to long-term care (adjusted odds ratio, 2.79; 95% CI, 2.11-3.79), and 1-year mortality (adjusted hazard ratio, 2.42; 95% CI, 2.09-2.80). Associations were maintained in patients with mild strokes. One in 5 patients with acute ischemic stroke did not have documented dysphagia screening, and patients with mild strokes were substantially less likely to have documented screening. Failing dysphagia screening was associated with poor outcomes, including in patients with mild strokes, highlighting the importance of dysphagia screening for all patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

  10. Compromised Wound Healing in Ischemic Type 2 Diabetic Rats.

    PubMed

    Yang, Peilang; Pei, Qing; Yu, Tianyi; Chang, Qingxuan; Wang, Di; Gao, Min; Zhang, Xiong; Liu, Yan

    2016-01-01

    Ischemia is one of the main epidemic factors and characteristics of diabetic chronic wounds, and exerts a profound effect on wound healing. To explore the mechanism of and the cure for diabetic impaired wound healing, we established a type 2 diabetic rat model. We used an 8 weeks high fat diet (HFD) feeding regimen followed by multiple injections of streptozotocin (STZ) at a dose of 10mg/kg to induce Wister rat to develop type 2 diabetes. Metabolic characteristics were assessed at the 5th week after the STZ injections to confirm the establishment of diabetes mellitus on the rodent model. A bipedicle flap, with length to width ratio 1.5, was performed on the back of the rat to make the flap area ischemic. Closure of excisional wounds on this bipedicle flap and related physiological and pathological changes were studied using histological, immunohistochemical, real time PCR and protein immunoblot approaches. Our results demonstrated that a combination of HFD feeding and a low dose of STZ is capable of inducing the rats to develop type 2 diabetes with noticeable insulin resistance, persistent hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol and high triglyceride levels. The excision wounds on the ischemic double pedicle flap showed deteriorative healing features comparing with non-ischemic diabetic wounds, including: delayed healing, exorbitant wound inflammatory response, excessive and prolonged ROS production and excessive production of MMPs. Our study suggested that HFD feeding combined with STZ injection could induce type 2 diabetes in rat. Our ischemic diabetic wound model is suitable for the investigation of human diabetic related wound repair; especically for diabetic chronic wounds.

  11. Angiogenesis-regulating microRNAs and ischemic stroke

    PubMed Central

    Yin, Ke-Jie; Hamblin, Milton; Chen, Y. Eugene

    2014-01-01

    Stroke is a leading cause of death and disability worldwide. Ischemic stroke is the dominant subtype of stroke and results from focal cerebral ischemia due to occlusion of major cerebral arteries. Thus, the restoration or improvement of reduced regional cerebral blood supply in a timely manner is very critical for improving stroke outcomes and post-stroke functional recovery. The recovery from ischemic stroke largely relies on appropriate restoration of blood flow via angiogenesis. Newly formed vessels would allow increased cerebral blood flow, thus increasing the amount of oxygen and nutrients delivered to affected brain tissue. Angiogenesis is strictly controlled by many key angiogenic factors in the central nervous system, and these molecules have been well-documented to play an important role in the development of angiogenesis in response to various pathological conditions. Promoting angiogenesis via various approaches that target angiogenic factors appears to be a useful treatment for experimental ischemic stroke. Most recently, microRNAs (miRs) have been identified as negative regulators of gene expression in a post-transcriptional manner. Accumulating studies have demonstrated that miRs are essential determinants of vascular endothelial cell biology/angiogenesis as well as contributors to stroke pathogenesis. In this review, we summarize the knowledge of stroke-associated angiogenic modulators, as well as the role and molecular mechanisms of stroke-associated miRs with a focus on angiogenesis-regulating miRs. Moreover, we further discuss their potential impact on miR-based therapeutics in stroke through targeting and enhancing post-ischemic angiogenesis. PMID:26156265

  12. Mechanical Thrombectomy in Acute Ischemic Stroke: A Systematic Review.

    PubMed

    Lambrinos, Anna; Schaink, Alexis K; Dhalla, Irfan; Krings, Timo; Casaubon, Leanne K; Sikich, Nancy; Lum, Cheemun; Bharatha, Aditya; Pereira, Vitor Mendes; Stotts, Grant; Saposnik, Gustavo; Kelloway, Linda; Xie, Xuanqian; Hill, Michael D

    2016-07-01

    Although intravenous thrombolysis increases the probability of a good functional outcome in carefully selected patients with acute ischemic stroke, a substantial proportion of patients who receive thrombolysis do not have a good outcome. Several recent trials of mechanical thrombectomy appear to indicate that this treatment may be superior to thrombolysis. We therefore conducted a systematic review and meta-analysis to evaluate the clinical effectiveness and safety of new-generation mechanical thrombectomy devices with intravenous thrombolysis (if eligible) compared with intravenous thrombolysis (if eligible) in patients with acute ischemic stroke caused by a proximal intracranial occlusion. We systematically searched seven databases for randomized controlled trials published between January 2005 and March 2015 comparing stent retrievers or thromboaspiration devices with best medical therapy (with or without intravenous thrombolysis) in adults with acute ischemic stroke. We assessed risk of bias and overall quality of the included trials. We combined the data using a fixed or random effects meta-analysis, where appropriate. We identified 1579 studies; of these, we evaluated 122 full-text papers and included five randomized control trials (n=1287). Compared with patients treated medically, patients who received mechanical thrombectomy were more likely to be functionally independent as measured by a modified Rankin score of 0-2 (odds ratio, 2.39; 95% confidence interval, 1.88-3.04; I2=0%). This finding was robust to subgroup analysis. Mortality and symptomatic intracerebral hemorrhage were not significantly different between the two groups. Mechanical thrombectomy significantly improves functional independence in appropriately selected patients with acute ischemic stroke.

  13. Thrombolysis in Chinese Ischemic Stroke Patients with Renal Dysfunction

    PubMed Central

    Lo, Wai Ting; Cheung, Chi Yuen; Li, Chung Ki; Chau, Ka Foon; Fong, Wing Chi

    2015-01-01

    Background Current data concerning the relationship between renal function and clinical outcome among stroke patients treated with intravenous thrombolytic therapy are conflicting. Our aim is to analyze whether the clinical outcome of Chinese ischemic stroke patients treated with thrombolytic therapy is affected by the presence of renal dysfunction. Methods Chinese patients who received intravenous thrombolytic therapy for acute ischemic stroke were recruited. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2. The primary outcome was independent function (modified Rankin Scale, mRS, 0-2) at 3 months, while secondary outcomes included early improvement of the National Institute of Health Stroke Scale (NIHSS) score of ≥4 points at 24 h, symptomatic intracerebral hemorrhage (ICH) within 36 h of treatment and 30-day mortality. Results A total of 199 patients were recruited, of whom 51.3% had renal dysfunction. There were no significant differences in functional independence at 3 months, NIHSS improvement at 24 h post-thrombolysis and 30-day mortality between patients with or without renal dysfunction. Multivariate analysis showed that eGFR as a continuous variable was not an independent risk factor for symptomatic ICH. Conclusion Chinese ischemic stroke patients with renal dysfunction who received thrombolytic therapy had clinical outcomes similar to those without renal dysfunction. PMID:26019713

  14. Acute bile duct ligation ameliorates ischemic renal failure.

    PubMed

    Jeyarajah, D Rohan; Kielar, Mariusz L; Zhou, Xin J; Zhang, Ying; Lu, Christopher Y

    2003-01-01

    Biliary obstruction affects the renal response to ischemia and also elicits a hepatic cytokine response. Using a murine model, we now test the hypothesis that these hepatic cytokines help determine the outcome of ischemic acute renal failure. C3H/HEN mice were subjected to bile duct ligation 24 h (ABDL) or 7 days (CBDL) prior to induction of acute ischemic renal failure (ARF). Serum creatinine (Scr), cytokine mRNA abundance, and renal histology were studied 24 h after renal ischemia. ABDL prior to ARF resulted in amelioration of renal injury (Scr 0.7 +/- 0.1 mg/dl compared to 2.5 +/- 0.1 mg/dl in sham/ARF group, (mean +/- SE, n = 11/group). CBDL exacerbated renal injury. Increased hepatic mRNA for interleukin-10 (IL10) and interleukin-1 receptor antagonist (IL1RA) was detected in the ABDL/ARF group but not in the CBDL/ARF group. These data suggest that hepatic production of IL10 and IL1RA in response to ABDL ameliorates ischemic ARF, an effect that is lost after several days of BDL. Our data support the concept that hepatic cytokines modulate renal injury. This adds a new dimension in our understanding of renal injury in the setting of hepatic disease. Copyright 2003 S. Karger AG, Basel

  15. Pituitary function and IGF-I levels following ischemic stroke.

    PubMed

    Boehncke, Sandra; Ackermann, Hanns; Badenhoop, Klaus; Sitzer, Matthias

    2011-01-01

    Pituitary dysfunction is a known complication of traumatic brain injury and subarachnoidal hemorrhage but there are few data about pituitary dysfunction as a complication of ischemic stroke. We prospectively studied patients 66-274 days after an ischemic stroke, evaluating the prevalence of pituitary dysfunction (by combined releasing hormone testing: GHRH, CRH), stroke severity, outcome and incidence of anxiety and depression. Thirty-two patients (82%) presented with some degree of pituitary dysfunction with predominantly impaired growth hormone response (79.5%) and secondary adrenal failure (14.6%). Abnormal anxiety and/or depression was found in 28.3 and 32.7% of the patients. NIHSS (National Institute of Health Stroke Scale) varied between 1 and 15. Improvement in neurological deficit (ΔNIHSS) correlated significantly with NIHSS at baseline (p < 0.001) but not with pituitary function. Patients with ischemic stroke may suffer from pituitary dysfunction with predominantly impaired growth hormone response and secondary adrenal failure. We suggest that patients who suffer from stroke should undergo pituitary testing. Copyright © 2010 S. Karger AG, Basel.

  16. Human umbilical mesenchymal stem cells promote recovery after ischemic stroke.

    PubMed

    Lin, Yu-Ching; Ko, Tsui-Ling; Shih, Yang-Hsin; Lin, Maan-Yuh Anya; Fu, Tz-Win; Hsiao, Hsiao-Sheng; Hsu, Jung-Yu C; Fu, Yu-Show

    2011-07-01

    Stroke is a cerebrovascular defect that leads to many adverse neurological complications. Current pharmacological treatments for stroke remain unclear in their effectiveness, whereas stem cell transplantation shows considerable promise. Previously, we have shown that human umbilical mesenchymal stem cells (HUMSCs) can differentiate into neurons in neuronal-conditioned medium. Here we evaluate the therapeutic potential of HUMSC transplantation for ischemic stroke in rats. Focal cerebral ischemia was produced by middle cerebral artery occlusion and reperfusion. The HUMSCs treated with neuronal-conditioned medium or not treated were transplanted into the ischemic cortex 24 hours after surgery. Histology and MRI revealed that rats implanted with HUMSCs treated with neuronal-conditioned medium or not treated exhibited a trend toward less infarct volume and significantly less atrophy compared with the control group, which received no HUMSCs. Moreover, rats receiving HUMSCs showed significant improvements in motor function, greater metabolic activity of cortical neurons, and better revascularization in the infarct cortex. Implanted HUMSCs, treated or not treated, survived in the infarct cortex for at least 36 days and released neuroprotective and growth-associated cytokines, including brain-derived neurotrophic factor, platelet-derived growth factor-AA, basic fibroblast growth factor, angiopoietin-2, CXCL-16, neutrophil-activating protein-2, and vascular endothelial growth factor receptor-3. Our results demonstrate the therapeutic benefits of HUMSC transplantation for ischemic stroke, likely due to the ability of the cells to produce growth-promoting factors. Thus, HUMSC transplantation may be an effective therapy in the future.

  17. Ginsenoside Rd and ischemic stroke; a short review of literatures☆

    PubMed Central

    Nabavi, Seyed Fazel; Sureda, Antoni; Habtemariam, Solomon; Nabavi, Seyed Mohammad

    2015-01-01

    Panax ginseng is a well-known economic medical plant that is widely used in Chinese traditional medicine. This species contains a unique class of natural products—ginsenosides. Recent clinical and experimental studies have presented numerous lines of evidence on the promising role of ginsenosides on different diseases including neurodegenerative diseases, cardiovascular diseases, and certain types of cancer. Nowadays, most of the attention has focused on ginsenoside Rd as a neuroprotective agent to attenuate ischemic stroke damages. Some of the evidence showed that ginsenoside Rd ameliorates ischemic stroke-induced damages through the suppression of oxidative stress and inflammation. Ginsenoside Rd can prolong neural cells' survival through the upregulation of the endogenous antioxidant system, phosphoinositide-3-kinase/AKT and extracellular signal-regulated protein kinase 1/2 pathways, preservation of mitochondrial membrane potential, suppression of the nuclear factor-kappa B, transient receptor potential melastatin, acid sensing ion channels 1a, poly(ADP-ribose) polymerase-1, protein tyrosine kinase activation, as well as reduction of cytochrome c-releasing and apoptosis-inducing factor. In the current work, we review the available reports on the promising role of ginsenoside Rd on ischemic stroke. We also discuss its chemistry, source, and the molecular mechanism underlying this effect. PMID:26869821

  18. Stress worsens endothelial function and ischemic stroke via glucocorticoids.

    PubMed

    Balkaya, Mustafa; Prinz, Vincent; Custodis, Florian; Gertz, Karen; Kronenberg, Golo; Kroeber, Jan; Fink, Klaus; Plehm, Ralph; Gass, Peter; Laufs, Ulrich; Endres, Matthias

    2011-11-01

    Chronic stress is associated with increased stroke risk. However, the underlying pathophysiological mechanisms are poorly understood. We examined the effects of chronic stress on endothelial function and ischemic brain injury in a mouse model. 129/SV mice were treated with glucocorticoid receptor antagonist mifepristone (25 mg kg(-1)/d) or vehicle and exposed to 28 days of chronic stress consisting of exposure to rat, restraint stress, and tail suspension. Heart rate and blood pressure were continuously recorded by telemetry. Endothelial nitric oxide synthase mRNA and protein expression as well as superoxide production and lipid hydroperoxides were quantified. Endothelium-dependent vasorelaxation was measured in aortic rings. Ischemic lesion volume was quantified after 30 minutes filamentous middle cerebral artery occlusion and 72 hours reperfusion. Chronic stress caused a significant increase in heart rate, impaired endothelium-dependent vasorelaxation, increased superoxide production, and reduced aortic and brain endothelial nitric oxide synthase levels. Animals exposed to chronic stress showed major increases in ischemic lesion size. These deleterious effects of stress were completely reversed by treatment with mifepristone. Chronic stress increases stroke vulnerability likely through endothelial dysfunction, which can be reversed by a glucocorticoid receptor antagonist.

  19. Neuroanatomical correlates of severe cardiac arrhythmias in acute ischemic stroke.

    PubMed

    Seifert, Frank; Kallmünzer, Bernd; Gutjahr, Isabell; Breuer, Lorenz; Winder, Klemens; Kaschka, Iris; Kloska, Stephan; Doerfler, Arnd; Hilz, Max-Josef; Schwab, Stefan; Köhrmann, Martin

    2015-05-01

    Neurocardiological interactions can cause severe cardiac arrhythmias in patients with acute ischemic stroke. The relationship between the lesion location in the brain and the occurrence of cardiac arrhythmias is still discussed controversially. The aim of the present study was to correlate the lesion location with the occurrence of cardiac arrhythmias in patients with acute ischemic stroke. Cardiac arrhythmias were systematically assessed in patients with acute ischemic stroke during the first 72 h after admission to a monitored stroke unit. Voxel-based lesion-symptom mapping (VLSM) was used to correlate the lesion location with the occurrence of clinically relevant severe arrhythmias. Overall 150 patients, 56 with right-hemispheric and 94 patients with a left-hemispheric lesion, were eligible to be included in the VLSM study. Severe cardiac arrhythmias were present in 49 of these 150 patients (32.7%). We found a significant association (FDR correction, q < 0.05) between lesions in the right insular, right frontal and right parietal cortex as well as the right amygdala, basal ganglia and thalamus and the occurrence of cardiac arrhythmias. Because left- and right-hemispheric lesions were analyzed separately, the significant findings rely on the 56 patients with right-hemispheric lesions. The data indicate that these areas are involved in central autonomic processing and that right-hemispheric lesions located to these areas are associated with an elevated risk for severe cardiac arrhythmias.

  20. Computer simulation of the reentrant cardiac arrhythmias in ischemic myocardium.

    PubMed

    Zhang, Hong; Yang, Lin; Jin, Yin-bin; Zhang, Zhen-xi; Huang, Yi-zhuo

    2005-09-30

    Computer simulation was performed to determine how reentrant activity could occur due to the spatial heterogeneity in refractoriness induced by the regional ischemia. Two regional ischemic models were developed by decreasing the intracellular ATP concentration, reducing conductance of the inward Na+ current and increasing the extracellular K+ concentration on the two-dimensional sheet. Operator splitting method was used to integrate the models. The vulnerability to reentry was estimated from the timings of premature stimuli on the constructed models, which could result in unidirectionally propagating action potentials. Two kinds of sustained spiral waves and their Pseudo-Electroscardiograms were observed in numerical simulation. The results showed that the dispersion of refractory period increased with ischemic aggravation, and led to augment of the vulnerable window. A permature stimulation within the vulnerable window could easily induce spiral reentry. The Pseudo-Electrocardiograms of the spiral waves exhibited monomorphic tachycardiac waveforms. Thus, the spatial heterogeneity in refractoriness could be a substrate for reentrant ventricular tachyarrhythmias on the regional ischemic tissue.

  1. Reperfusion therapies for acute ischemic stroke: an update.

    PubMed

    Dorado, Laura; Millán, Mònica; Dávalos, Antoni

    2014-11-01

    Acute ischemic stroke is a major cause of morbidity and mortality in developed countries. Intravenous thrombolysis with tissue plasminogen activator (tPA) within 4.5 hours of symptoms onset significantly improves clinical outcomes in patients with acute ischemic stroke. This narrow window for treatment leads to a small proportion of eligible patients to be treated. Intravenous or intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries have been investigated or are currently being explored to increase patient eligibility and to improve arterial recanalization and clinical outcome. New retrievable stent-based devices offer higher revascularization rates with shorter time to recanalization and are now generally preferred to first generation thrombectomy devices such as Merci Retriever or Penumbra System. These devices have been shown to be effective for opening up occluded vessels in the brain but its efficacy for improving outcomes in patients with acute stroke has not yet been demonstrated in a randomized clinical trial. We summarize the results of the major systemic thrombolytic trials and the latest trials employing different endovascular approaches to ischemic stroke.

  2. Innate immune inflammatory response in the acutely ischemic myocardium.

    PubMed

    Deftereos, Spyridon; Angelidis, Christos; Bouras, Georgios; Raisakis, Konstantinos; Gerckens, Ulrich; Cleman, Michael W; Giannopoulos, Georgios

    2014-01-01

    The "holy grail" of modern interventional cardiology is the salvage of viable myocardial tissue in the distribution of an acutely occluded coronary artery. Thrombolysis and percutaneous coronary interventions, provided they can be delivered on time, can interrupt the occlusion and save tissue. At the same time restoring the patency of the coronary vessels and providing the ischemic myocardium with blood can cause additional tissue damage. A key element of ischemic and reperfusion injury and major determinant of the evolution of damage in the injured myocardium is the inflammatory response. The innate immune system initiates and directs this response which is a prerequisite for subsequent healing. The complement cascade is set in motion following the release of subcellular membrane constituents. Endogenous 'danger' signals known as danger-associated molecular patterns (DAMPs) released from ischemic and dying cells alert the innate immune system and activate several signal transduction pathways through interactions with the highly conserved Toll like receptors (TLRs). Reactive oxygen species (ROS) generation directly induces pro-inflammatory cascades and triggers formation of the inflammasome. The challenge lies into designing strategies that specifically block the inflammatory cascades responsible for tissue damage without affecting those concerned with tissue healing.

  3. Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage.

    PubMed

    Puentes, Sandra; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Yoshimoto, Yuhei; Mikuni, Masahiko; Imai, Hideaki; Ishizaki, Yasuki

    2012-08-21

    Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia.

  4. Effect of glutathion pretreatment on hypothermic ischemic cardioplegia.

    PubMed

    Amano, J; Sunamori, M; Okamura, T; Suzuki, A

    1982-01-01

    Glutathion (GSH) plays an important role in maintenance of the redox state of the myocardium and acts as the membrane stabilizer. Seventeen patients who underwent cardiac surgery were subjected to cardiopulmonary bypass (CPB) and ischemic cardioplegia. The effect of GSH on ischemic myocardium was evaluated by serum lysosomal enzymes (acid phosphatase, beta-glucuronidase), isoenzymes of creatine phosphokinase (MB-CPK) and aspartate aminotransferase (m-GOT). standard CPB was instituted and systemic hypothermia was employed. GSH was administered to 8 patients in a dose of 200 mg/kg i.v. prior to institution of CPB. Mixed venous blood was sampled before administration of GSH, 10 min after institution of CPB and 0, 1, 6, 24 and 48 hr of reperfusion period following cardioplegia. Activity of acid phosphatase and beta-glucuronidase were significantly suppressed in the GSH-treated group compared to the non-treated group at 24 hours of reperfusion and immediately after aortic unclamping, respectively. Serum MB-CPK levels remained stable during reperfusion, but in the non-treated group, the level increased significantly at 6 hours of reperfusion. Increment of serum m-GOT levels was significantly suppressed at 1, 6 and 24 hours of reperfusion, compared to the non-treated group. These data suggest that pretreatment of GSH can protect the myocardium subjected to CPB from ischemic insult.

  5. Protein methionine oxidation augments reperfusion injury in acute ischemic stroke

    PubMed Central

    Gu, Sean X.; Blokhin, Ilya O.; Wilson, Katina M.; Dhanesha, Nirav; Doddapattar, Prakash; Grumbach, Isabella M.; Chauhan, Anil K.; Lentz, Steven R.

    2016-01-01

    Reperfusion injury can exacerbate tissue damage in ischemic stroke, but little is known about the mechanisms linking ROS to stroke severity. Here, we tested the hypothesis that protein methionine oxidation potentiates NF-κB activation and contributes to cerebral ischemia/reperfusion injury. We found that overexpression of methionine sulfoxide reductase A (MsrA), an antioxidant enzyme that reverses protein methionine oxidation, attenuated ROS-augmented NF-κB activation in endothelial cells, in part, by protecting against the oxidation of methionine residues in the regulatory domain of calcium/calmodulin-dependent protein kinase II (CaMKII). In a murine model, MsrA deficiency resulted in increased NF-κB activation and neutrophil infiltration, larger infarct volumes, and more severe neurological impairment after transient cerebral ischemia/reperfusion injury. This phenotype was prevented by inhibition of NF-κB or CaMKII. MsrA-deficient mice also exhibited enhanced leukocyte rolling and upregulation of E-selectin, an endothelial NF-κB–dependent adhesion molecule known to contribute to neurovascular inflammation in ischemic stroke. Finally, bone marrow transplantation experiments demonstrated that the neuroprotective effect was mediated by MsrA expressed in nonhematopoietic cells. These findings suggest that protein methionine oxidation in nonmyeloid cells is a key mechanism of postischemic oxidative injury mediated by NF-κB activation, leading to neutrophil recruitment and neurovascular inflammation in acute ischemic stroke. PMID:27294204

  6. Targeting MMP-2 to treat ischemic heart injury.

    PubMed

    Hughes, Bryan G; Schulz, Richard

    2014-07-01

    Matrix metalloproteinase (MMPs) are long understood to be involved in remodeling of the extracellular matrix. However, over the past decade, it has become clear that one of the most ubiquitous MMPs, MMP-2, has numerous intracellular targets in cardiac myocytes. Notably, MMP-2 proteolyzes components of the sarcomere, and its intracellular activity contributes to ischemia-reperfusion injury of the heart. Together with the well documented role played by MMPs in the myocardial remodeling that occurs following myocardial infarction, this has led to great interest in targeting MMPs to treat cardiac ischemic injury. In this review we will describe the expanding understanding of intracellular MMP-2 biology, and how this knowledge may lead to improved treatments for ischemic heart injury. We also critically review the numerous preclinical studies investigating the effects of MMP inhibition in animal models of myocardial infarction and ischemia-reperfusion injury, as well as the recent clinical trials that are part of the effort to translate these results into clinical practice. Acknowledging the disappointing results of past clinical trials of MMP inhibitors for other diseases, we discuss the need for carefully designed preclinical and clinical studies to avoid mistakes that have been previously made. We conclude that inhibition of MMPs, and in particular MMP-2, shows promise as a therapy to prevent the progression from ischemic injury to heart failure. However, it is critical that the full breadth of MMP-2 biology be taken into account as such therapies are developed.

  7. Asymmetric Dimethyarginine as Marker and Mediator in Ischemic Stroke

    PubMed Central

    Chen, Shufen; Li, Na; Deb-Chatterji, Milani; Dong, Qiang; Kielstein, Jan T.; Weissenborn, Karin; Worthmann, Hans

    2012-01-01

    Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, is known as mediator of endothelial cell dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. Accordingly, clinical studies found evidence that increased ADMA levels are associated with a higher risk of cerebrovascular events. After the acute event of ischemic stroke, levels of ADMA and its analog symmetric dimethylarginine (SDMA) are elevated through augmentation of protein methylation and oxidative stress. Furthermore, cleavage of ADMA through dimethylarginine dimethylaminohydrolases (DDAHs) is reduced. This increase of dimethylarginines might be predictive for adverse clinical outcome. However, the definite role of ADMA after acute ischemic stroke still needs to be clarified. On the one hand, ADMA might contribute to brain injury by reduction of cerebral blood flow. On the other hand, ADMA might be involved in NOS-induced oxidative stress and excitotoxic neuronal death. In the present review, we highlight the current knowledge from clinical and experimental studies on ADMA and its role for stroke risk and ischemic brain injury in the hyperacute stage after stroke. Finally, further studies are warranted to unravel the relevance of the close association of dimethylarginines with stroke. PMID:23443106

  8. Peripheral blood stem cell transplantation for ischemic femoral head necrosis.

    PubMed

    Song, H-J; Lan, B-Sh; Cheng, B; Zhang, K-F; Yan, H-W; Wang, W-Zh; Gao, Z-Q

    2010-06-01

    Avascular necrosis of the femoral head (ANFH) is a highly mutilating disease. There is no effective way to treat femoral head ischemia. This study was designed to show the curative effects of peripheral blood stem cell transplantation to induce vascular regeneration and improve ischemic femoral head necrosis in rabbits. Twenty New Zealand white rabbits underwent ischemic femoral head necrosis in both hindlimbs using liquid-nitrogen refrigeration. One cohort of rats was intraperitoneally injected with granulocyte-specific colony-stimulating factor (250 microg/kg/d), and control animals received equivalent saline solution. The right side was used as the transplantation group and the left as the control. After separation of peripheral blood, a stem cell suspension was poured into the right femoral artery and saline solution into the left femoral artery. At 4 weeks after peripheral stem cell transplantation, standing ability and activity of the the transplanted right hindlimb were remarkably improved, but there were no obvious changes in the control limbs. The experimental rabbits underwent arteriography of bilateral femoral heads, which indicated increased and thickened blood supply to the transplanted right hindlimb compared with the left control. Peripheral blood stem cell transplantation improved ischemic femoral head necrosis.

  9. Ischemic necrosis following clubfoot surgery: the purple hallux sign.

    PubMed

    David, R Hootnick; Packard, David S; Levinsohn, E Mark; Berkowitz, Scott A; Aronsson, David D; Crider, Russell J

    2004-09-01

    Ischemic necrosis, which develops rarely after clubfoot surgery, may have a vascular etiology, since many idiopathic and neurogenic clubfeet have congenital deficiency of the anterior tibial and dorsalis pedis arteries. Dorsalis pedis deficiency is demonstrated more frequently in those clubfeet showing greater deformity. Substantial hypoplasia of the profunda femoris and posterior and anterior tibial arteries was evident in the affected limb of a patient in this series who underwent postoperative arteriography. Herein, we report massive necrosis in seven limbs of six patients after clubfoot surgery and have combined this series with seven previously published cases. Additional cases support our hypothesis that arterial deficiencies put some postoperative clubfeet at risk of perioperative ischemic necrosis. Necrosis occurs in those regions supplied by the congenitally diminished anterior tibial and dorsalis pedis arteries. Knowing that children with congenital vascular deficiency are at risk for ischemic necrosis, surgeons should be alert to the subtle, early signs of ischemia and be prepared to prevent or ameliorate the consequences of this condition. Since hypoperfusion in these postoperative feet is a surgical emergency, we propose clinical guidelines for treatment for this phenomenon, which we have named the purple hallux sign.

  10. Prevalence of Cerebral Microbleeds in Thai Patients with Ischemic Stroke.

    PubMed

    Potigumjon, Artit; Watcharakorn, Arvemas; Dharmasaroja, Pornpatr A

    2017-01-01

    With the widespread use of magnetic resonance imaging (MRI), cerebral microbleeds (CMBs) are commonly detected. Ethnicity seems to play a role in the prevalence of CMB, with higher prevalence in participants from Asian origin. The purpose of the study is to look for the prevalence of CMBs and associated factors in Thai patients with ischemic stroke. Patients with acute ischemic stroke who had MRI and magnetic resonance angiography during January-August 2014 were included in the study. T2*-weighted gradient-recalled echo was used to define CMBs. Baseline characteristics, stroke subtypes, and severity of white matter lesions were compared between patients with and without CMBs. Two hundred patients were included in the study. Mean age of the patients was 61-year-old. Mean National Institutes of Health Stroke Scale was 8. The prevalence of CMBs was 20% (39/200 patients). Hypertension (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.07-8.68, P = 0.037), and moderate-to-severe white matter lesions (Fazekas 2-3, OR 7.61, 95% CI 3.06-18.95, P < 0.001) were related to the presence of CMBs. CMBs were found in 20% of patients with ischemic stroke, which was lower than those reported from Japanese studies but comparable to a Chinese study. CMBs were associated with hypertension and severity of the white matter lesions.

  11. Prevalence of Cerebral Microbleeds in Thai Patients with Ischemic Stroke

    PubMed Central

    Potigumjon, Artit; Watcharakorn, Arvemas; Dharmasaroja, Pornpatr A.

    2017-01-01

    Background: With the widespread use of magnetic resonance imaging (MRI), cerebral microbleeds (CMBs) are commonly detected. Ethnicity seems to play a role in the prevalence of CMB, with higher prevalence in participants from Asian origin. The purpose of the study is to look for the prevalence of CMBs and associated factors in Thai patients with ischemic stroke. Methods: Patients with acute ischemic stroke who had MRI and magnetic resonance angiography during January–August 2014 were included in the study. T2*-weighted gradient-recalled echo was used to define CMBs. Baseline characteristics, stroke subtypes, and severity of white matter lesions were compared between patients with and without CMBs. Results: Two hundred patients were included in the study. Mean age of the patients was 61-year-old. Mean National Institutes of Health Stroke Scale was 8. The prevalence of CMBs was 20% (39/200 patients). Hypertension (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.07–8.68, P = 0.037), and moderate-to-severe white matter lesions (Fazekas 2–3, OR 7.61, 95% CI 3.06–18.95, P < 0.001) were related to the presence of CMBs. Conclusions: CMBs were found in 20% of patients with ischemic stroke, which was lower than those reported from Japanese studies but comparable to a Chinese study. CMBs were associated with hypertension and severity of the white matter lesions. PMID:28479795

  12. Increased hematocrit mitigates ischemic renal damage in the splenectomized dog.

    PubMed

    Bell, R D; Mandal, A K

    1989-03-01

    Splenectomy (SPLX) prevents ischemic acute tubular necrosis (ATN) and peritubular capillary (PTC) congestion. This study attempts to reverse the protective effect of splenectomy in the ischemic model of ATN by increasing hematocrit before inducing ATN. Sham-SPLX, SPLX, and SPLX dogs given packed red cells to elevate hematocrit by 30% (SPLX-high hematocrit) received bilateral renal artery obstruction (RAO) for 120 minutes. Renal function was tested for 6 days post-RAO. Hematocrit in the SPLX-high hematocrit group was greater (p less than .05) than the SPLX-RAO group but did not differ from the non-SPLX group. All groups had different (p less than .05) serum creatinine levels for 48 hours post-RAO, and untreated animals differed from all the others at 144 hours. Serum creatinine was highest in untreated, lowest in SPLX-high hematocrit, and intermediate in noninfused SPLX animals. The same pattern was observed in blood urea nitrogen, creatinine clearance and renal histopathology. Fractional excretion of sodium in the SPLX groups was six times that in the intact animals (p less than .05), irrespective of hematocrit level. We conclude that increased hematocrit is protective in ischemic ATN, and does not promote PTC congestion or ATN in the SPLX animal. In addition, the protective effect of splenectomy may be mediated, in part, by mechanism(s) that alter sodium transport or osmolar excretion.

  13. Sesamin attenuates neurotoxicity in mouse model of ischemic brain stroke.

    PubMed

    Ahmad, Saif; Elsherbiny, Nehal M; Haque, Rizwanul; Khan, M Badruzzaman; Ishrat, Tauheed; Shah, Zahoor A; Khan, Mohammad M; Ali, Mehboob; Jamal, Arshad; Katare, Deepshikha Pande; Liou, Gregory I; Bhatia, Kanchan

    2014-12-01

    Stroke is a severe neurological disorder characterized by the abrupt loss of blood circulation into the brain resulting into wide ranging brain and behavior abnormalities. The present study was designed to evaluate molecular mechanism by which sesamin (SES) induces neuroprotection in mouse model of ischemic stroke. The results of this study demonstrate that SES treatment (30 mg/kg bwt) significantly reduced infarction volume, lipid per-oxidation, cleaved-caspase-3 activation, and increased GSH activity following MCAO in adult male mouse. SES treatment also diminished iNOS and COX-2 protein expression, and significantly restored SOD activity and protein expression level in the ischemic cortex of the MCAO animals. Furthermore, SES treatment also significantly reduced inflammatory and oxidative stress markers including Iba1, Nox-2, Cox-2, peroxynitrite compared to placebo MCAO animals. Superoxide radical production, as studied by DHE staining method, was also significantly reduced in the ischemic cortex of SES treated compared to placebo MCAO animals. Likewise, downstream effects of superoxide free radicals i.e. MAPK/ERK and P38 activation was also significantly attenuated in SES treated compared to placebo MCAO animals. In conclusion, these results suggest that SES induces significant neuroprotection, by ameliorating many signaling pathways activated/deactivated following cerebral ischemia in adult mouse. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Topical fentanyl stimulates healing of ischemic wounds in diabetic rats

    PubMed Central

    FAROOQUI, Mariya; ERICSON, Marna E; GUPTA, Kalpna

    2016-01-01

    Background Topically applied opioids promote angiogenesis and healing of ischemic wounds in rats. We examined if topical fentanyl stimulates wound healing in diabetic rats by stimulating growth-promoting signaling, angiogenesis, lymphangiogenesis and nerve regeneration. Methods We used Zucker diabetic fatty rats that develop obesity and diabetes on a high fat diet due to a mutation in the Leptin receptor. Fentanyl blended with hydrocream was applied topically on ischemic wounds twice daily, and wound closure was analyzed regularly. Wound histology was analyzed by hematoxylin and eosin staining. Angiogenesis, lymphangiogenesis, nerve fibers and phospho-PDGFR-β were visualized by CD31-, lymphatic vessel endothelium-1, protein gene product 9.5- and anti-phospho PDGFR-β-immunoreactivity, respectively. Nitric oxide synthase (NOS) and PDGFR-β signaling were analyzed using Western immunoblotting. Results Fentanyl significantly promoted wound closure as compared to PBS. Histology scores were significantly higher in fentanyl-treated wounds, indicative of increased granulation tissue formation, reduced edema and inflammation, and increased matrix deposition. Fentanyl treatment resulted in increased wound angiogenesis, lymphatic vasculature, nerve fibers, nitric oxide, NOS and PDGFR-β signaling as compared to PBS. Phospho PDGFR-β co-localized with CD31 co-staining for vasculature. Conclusions Topically applied fentanyl promotes closure of ischemic wounds in diabetic rats. Increased angiogenesis, lymphangiogenesis, peripheral nerve regeneration, NO and PDGFR-β signaling are associated with fentanyl-induced tissue remodeling and wound healing. PMID:25266258

  15. Reperfusion Therapies for Acute Ischemic Stroke: An Update

    PubMed Central

    Dorado, Laura; Millán, Mònica; Dávalos, Antoni

    2014-01-01

    Acute ischemic stroke is a major cause of morbidity and mortality in developed countries. Intravenous thrombolysis with tissue plasminogen activator (tPA) within 4.5 hours of symptoms onset significantly improves clinical outcomes in patients with acute ischemic stroke. This narrow window for treatment leads to a small proportion of eligible patients to be treated. Intravenous or intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries have been investigated or are currently being explored to increase patient eligibility and to improve arterial recanalization and clinical outcome. New retrievable stent-based devices offer higher revascularization rates with shorter time to recanalization and are now generally preferred to first generation thrombectomy devices such as Merci Retriever or Penumbra System. These devices have been shown to be effective for opening up occluded vessels in the brain but its efficacy for improving outcomes in patients with acute stroke has not yet been demonstrated in a randomized clinical trial. We summarize the results of the major systemic thrombolytic trials and the latest trials employing different endovascular approaches to ischemic stroke. PMID:24646159

  16. Design and rationale for examining neuroimaging genetics in ischemic stroke

    PubMed Central

    Giese, Anne-Katrin; Schirmer, Markus D.; Donahue, Kathleen L.; Cloonan, Lisa; Irie, Robert; Winzeck, Stefan; Bouts, Mark J.R.J.; McIntosh, Elissa C.; Mocking, Steven J.; Dalca, Adrian V.; Sridharan, Ramesh; Xu, Huichun; Frid, Petrea; Giralt-Steinhauer, Eva; Holmegaard, Lukas; Roquer, Jaume; Wasselius, Johan; Cole, John W.; McArdle, Patrick F.; Broderick, Joseph P.; Jimenez-Conde, Jordi; Jern, Christina; Kissela, Brett M.; Kleindorfer, Dawn O.; Lemmens, Robin; Lindgren, Arne; Meschia, James F.; Rundek, Tatjana; Sacco, Ralph L.; Schmidt, Reinhold; Sharma, Pankaj; Slowik, Agnieszka; Thijs, Vincent; Woo, Daniel; Worrall, Bradford B.; Kittner, Steven J.; Mitchell, Braxton D.; Rosand, Jonathan; Golland, Polina; Wu, Ona

    2017-01-01

    Objective: To describe the design and rationale for the genetic analysis of acute and chronic cerebrovascular neuroimaging phenotypes detected on clinical MRI in patients with acute ischemic stroke (AIS) within the scope of the MRI–GENetics Interface Exploration (MRI-GENIE) study. Methods: MRI-GENIE capitalizes on the existing infrastructure of the Stroke Genetics Network (SiGN). In total, 12 international SiGN sites contributed MRIs of 3,301 patients with AIS. Detailed clinical phenotyping with the web-based Causative Classification of Stroke (CCS) system and genome-wide genotyping data were available for all participants. Neuroimaging analyses include the manual and automated assessments of established MRI markers. A high-throughput MRI analysis pipeline for the automated assessment of cerebrovascular lesions on clinical scans will be developed in a subset of scans for both acute and chronic lesions, validated against gold standard, and applied to all available scans. The extracted neuroimaging phenotypes will improve characterization of acute and chronic cerebrovascular lesions in ischemic stroke, including CCS subtypes, and their effect on functional outcomes after stroke. Moreover, genetic testing will uncover variants associated with acute and chronic MRI manifestations of cerebrovascular disease. Conclusions: The MRI-GENIE study aims to develop, validate, and distribute the MRI analysis platform for scans acquired as part of clinical care for patients with AIS, which will lead to (1) novel genetic discoveries in ischemic stroke, (2) strategies for personalized stroke risk assessment, and (3) personalized stroke outcome assessment. PMID:28852707

  17. Xanthine dehydrogenase to xanthine oxidase conversion in ischemic rat intestine

    SciTech Connect

    McKelvey, T.G.; Engerson, T.D.; Elmore, C.R.; Jones, H.P. )

    1990-02-26

    The ischemic conversion of the NADH-producing xanthine dehydrogenase (XDH) to an oxidase form, that produces both superoxide radical and hydrogen peroxide, has been proposed as an important step in initiating oxygen radical-mediated ischemia-reperfusion injury. It has also been reported that two forms of converted oxidase are produced in ischemic rat liver; a reversible xanthine oxidase produced through sulfhydryl oxidation, that can be reconverted to XDH by incubation with 10mM dithiothreitol (Dtt) at 37{degrees}C, and a Dtt-irreversible oxidase produced via proteolysis. The authors report that increased oxidase in the ischemic rat intestine results from significant increases in both the Dtt-reversible and Dtt-irreversible forms of xanthine oxidase. Total oxidase activity (Irreversible + Dtt-reversible) was 19% of the total enzyme activity (XDH + XO) in control ileum and distal jejunum, increased to 26% after 1 hour of ischemia at 37{degrees}C, and significantly to 36% after 1.5 hours. After 3 hours 73% of the activity was in the oxidase form. Irreversible oxidase comprised 15% of the total activity in control intestine, significantly increased to 25% after 2 hours, and further to 42% after 3 hours. Dtt-reversible oxidase was 3% of the total activity in controls, increased to 13% after 1.5 hours, and significantly to 29% after 2 hours.

  18. Elevated body temperature in ischemic stroke associated with neurological improvement.

    PubMed

    Khanevski, A N; Naess, H; Thomassen, L; Waje-Andreassen, U; Nacu, A; Kvistad, C E

    2017-11-01

    Some studies suggest that high body temperature within the first few hours of ischemic stroke onset is associated with improved outcome. We hypothesized an association between high body temperature on admission and detectable improvement within 6-9 hours of stroke onset. Consecutive ischemic stroke patients with NIHSS scores obtained within 3 hours and in the interval 6-9 hours after stroke onset were included. Body temperature was measured on admission. A total of 315 patients with ischemic stroke were included. Median NIHSS score on admission was 6. Linear regression showed that NIHSS score 6-9 hours after stroke onset was inversely associated with body temperature on admission after adjusting for confounders including NIHSS score <3 hours after stroke onset (P<.001). The same result was found in patients with proximal middle cerebral occlusion on admission. We found an inverse association between admission body temperature and neurological improvement within few hours after admission. This finding may be limited to patients with documented proximal middle cerebral artery occlusion on admission and suggests a beneficial effect of higher body temperature on clot lysis within the first three hours. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke.

    PubMed

    Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro

    2010-07-08

    Cannabis contains the psychoactive component delta⁸-tetrahydrocannabinol (delta⁸-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta⁸-THC and other cannabinoid CB₁ receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta⁸-THC also mediates psychological effects through the activation of the CB₁ receptor in the central nervous system. In addition to the CB₁ receptor agonists, cannabis also contains therapeutically active components which are CB₁ receptor independent. Of the CB₁ receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson's disease, Alzheimer's disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB₁ receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.

  20. Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

    PubMed Central

    Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro

    2010-01-01

    Cannabis contains the psychoactive component delta9-tetrahydrocannabinol (delta9-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke. PMID:27713349

  1. Do energy drinks cause epileptic seizure and ischemic stroke?

    PubMed

    Dikici, Suber; Saritas, Ayhan; Besir, Fahri Halit; Tasci, Ahmet Hakan; Kandis, Hayati

    2013-01-01

    Energy drinks are popular among young individuals and marketed to college students, athletes, and active individuals between the ages of 21 and 35 years. We report a case that had ischemic stroke and epileptic seizure after intake of energy drink with alcohol. To the best of our knowledge, the following case is the first report of ischemic stroke after intake of energy drink. A previously healthy 37-year-old man was brought to the emergency department after a witnessed tonic-clonic seizure. According to his wife's testimony, just before loss of consciousness, the patient had been drinking 3 boxes of energy drinks (Redbull, Istanbul, Turkey, 250 mL) with vodka on an empty stomach. He did not have a history of seizures, head trauma, or family history of seizures or another disease. In cranial diffusion magnetic resonance imaging, there were hyperintense signal changes in bilateral occipital area (more pronounced in the left occipital lobe), right temporal lobe, frontal lobe, and posterior parietal lobe. All tests associated with possible etiologic causes of ischemic stroke in young patients were negative. Herein, we want to attract attention to adverse effect of energy drink usage.

  2. Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke

    PubMed Central

    Liu, Zhongwu; Chopp, Michael

    2015-01-01

    Astrocytes are the most abundant cell type within the central nervous system. They play essential roles in maintaining normal brain function, as they are a critical structural and functional part of the tripartite synapses and the neurovascular unit, and communicate with neurons, oligodendrocytes and endothelial cells. After an ischemic stroke, astrocytes perform multiple functions both detrimental and beneficial, for neuronal survival during the acute phase. Aspects of the astrocytic inflammatory response to stroke may aggravate the ischemic lesion, but astrocytes also provide benefit for neuroprotection, by limiting lesion extension via anti-excitotoxicity effects and releasing neurotrophins. Similarly, during the late recovery phase after stroke, the glial scar may obstruct axonal regeneration and subsequently reduce the functional outcome; however, astrocytes also contribute to angiogenesis, neurogenesis, synaptogenesis, and axonal remodeling, and thereby promote neurological recovery. Thus, the pivotal involvement of astrocytes in normal brain function and responses to an ischemic lesion designates them as excellent therapeutic targets to improve functional outcome following stroke. In this review, we will focus on functions of astrocytes and astrocyte-mediated events during stroke and recovery. We will provide an overview of approaches on how to reduce the detrimental effects and amplify the beneficial effects of astrocytes on neuroprotection and on neurorestoration post stroke, which may lead to novel and clinically relevant therapies for stroke. PMID:26455456

  3. Migraine Mutations Increase Stroke Vulnerability by Facilitating Ischemic Depolarizations

    PubMed Central

    Eikermann-Haerter, Katharina; Lee, Jeong Hyun; Yuzawa, Izumi; Liu, Christina H.; Zhou, Zhipeng; Shin, Hwa Kyoung; Zheng, Yi; Qin, Tao; Kurth, Tobias; Waeber, Christian; Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.; Moskowitz, Michael A.; Ayata, Cenk

    2012-01-01

    Background Migraine is an independent risk factor for stroke. Mechanisms underlying this association are unclear. Familial hemiplegic migraine (FHM), a migraine subtype that also carries an increased stroke risk, is a useful model for common migraine phenotypes because of shared aura and headache features, trigger factors, and underlying glutamatergic mechanisms. Methods and Results Here, we show that FHM type 1 (FHM1) mutations in CaV2.1 voltage-gated Ca2+ channels render the brain more vulnerable to ischemic stroke. Compared to wild-type, two FHM1 mutant mouse strains developed earlier onset of anoxic depolarization and more frequent peri-infarct depolarizations, associated with rapid expansion of infarct core on diffusion-weighted MRI and larger perfusion deficits on laser speckle flowmetry. Cerebral blood flow required for tissue survival was higher in the mutants, leading to infarction with milder ischemia. As a result, mutants developed larger infarcts and worse neurological outcomes after stroke, which were selectively attenuated by a glutamate receptor antagonist. Conclusions We propose that enhanced susceptibility to ischemic depolarizations akin to spreading depression predisposes migraineurs to infarction during mild ischemic events, thereby increasing the stroke risk. PMID:22144569

  4. Imaging biomarkers in acute ischemic stroke trials: a systematic review.

    PubMed

    Harston, G W J; Rane, N; Shaya, G; Thandeswaran, S; Cellerini, M; Sheerin, F; Kennedy, J

    2015-05-01

    Imaging biomarkers are increasingly used to provide a better understanding of the pathophysiology of acute ischemic stroke. However, this approach of routinely using imaging biomarkers to inform treatment decisions has yet to be translated into successful randomized trials. The aim of this study was to systematically review the use of imaging biomarkers in randomized controlled trials in patients with acute ischemic stroke, exploring the purposes for which the imaging biomarkers were used. We performed a systematic review of imaging biomarkers used in randomized controlled trials of acute ischemic stroke, in which a therapeutic intervention was trialed within 48 hours of symptom onset. Data bases searched included MEDLINE, EMBASE, strokecenter.org, and the Virtual International Stroke Trials Archive (1995-2014). Eighty-four studies met the criteria, of which 49 used imaging to select patients; 31, for subgroup analysis; and 49, as an outcome measure. Imaging biomarkers were broadly used for 8 purposes. There was marked heterogeneity in the definitions and uses of imaging biomarkers and significant publication bias among post hoc analyses. Imaging biomarkers offer the opportunity to refine the trial cohort by minimizing participant variation, to decrease sample size, and to personalize treatment approaches for those who stand to benefit most. However, within imaging modalities, there has been little consistency between stroke trials. Greater effort to prospectively use consistent imaging biomarkers should help improve the development of novel treatment strategies in acute stroke and improve comparison between studies. © 2015 by American Journal of Neuroradiology.

  5. [Technical standards for the interventional treatment of acute ischemic stroke].

    PubMed

    Möhlenbruch, M A; Bendszus, M

    2015-10-01

    Acute ischemic stroke is the leading cause of acquired disability and its treatment is still a major challenge. For more than a decade, various mechanical devices have been developed for the recanalization of proximal artery occlusions in acute ischemic stroke but most of them have been approved for clinical use, only on the basis of uncontrolled case series. Intravenous thrombolysis with recombinant tissue-specific plasminogen activator administered (iv rtPA) within 4.5 h of symptom onset is so far the only approved medicinal treatment in the acute phase of cerebral infarction. With the introduction of stent retrievers, mechanical thrombectomy has demonstrated substantial rates of partial or complete arterial recanalization and improved outcomes compared with iv rtPA and best medical treatment alone in multiple randomized clinical trials in select patients with acute ischemic stroke and proximal artery occlusions. This review discusses the evolution of endovascular stroke therapy followed by a discussion of the current technical standards of mechanical thrombectomy that have to be considered during endovascular stroke therapy and the updated treatment recommendations of the ESO Karolinska stroke update.

  6. Targeting neutrophils in ischemic stroke: translational insights from experimental studies

    PubMed Central

    Jickling, Glen C; Liu, DaZhi; Ander, Bradley P; Stamova, Boryana; Zhan, Xinhua; Sharp, Frank R

    2015-01-01

    Neutrophils have key roles in ischemic brain injury, thrombosis, and atherosclerosis. As such, neutrophils are of great interest as targets to treat and prevent ischemic stroke. After stroke, neutrophils respond rapidly promoting blood–brain barrier disruption, cerebral edema, and brain injury. A surge of neutrophil-derived reactive oxygen species, proteases, and cytokines are released as neutrophils interact with cerebral endothelium. Neutrophils also are linked to the major processes that cause ischemic stroke, thrombosis, and atherosclerosis. Thrombosis is promoted through interactions with platelets, clotting factors, and release of prothrombotic molecules. In atherosclerosis, neutrophils promote plaque formation and rupture by generating oxidized-low density lipoprotein, enhancing monocyte infiltration, and degrading the fibrous cap. In experimental studies targeting neutrophils can improve stroke. However, early human studies have been met with challenges, and suggest that selective targeting of neutrophils may be required. Several properties of neutrophil are beneficial and thus may important to preserve in patients with stroke including antimicrobial, antiinflammatory, and neuroprotective functions. PMID:25806703

  7. Treatment of ischemic leg ulcers with pentoxifylline: a case report and theoretical considerations.

    PubMed

    Velanovich, V; Fahey, M J

    1990-07-01

    Ischemic ulcers remain difficult to treat. We describe a patient with bilateral ischemic leg ulcers treated preoperatively with pentoxifylline. She had a successful skin graft with no rejection of the graft. The theoretical advantage of treatment with pentoxifylline is discussed, with emphasis not only on its hemorheological properties, but also on its actions on the prostaglandin pathway, platelet aggregation, and thrombosis. We suggest that preoperative pentoxifylline treatment may be a useful adjunct in the closure of ischemic ulcers.

  8. The effect of ischemic preconditioning on the recovery of skeletal muscle following tourniquet ischemia.

    PubMed

    Whetzel, T P; Stevenson, T R; Sharman, R B; Carlsen, R C

    1997-12-01

    It has been well documented that ischemic preconditioning limits ischemic-reperfusion injury in cardiac muscle, but the ability of ischemic preconditioning to limit skeletal muscle injury is less clear. Previous reports have emphasized the beneficial effects of ischemic preconditioning on skeletal muscle structure and capillary perfusion but have not evaluated muscle function. We investigated the morphologic and functional consequences of ischemic preconditioning, followed by a 2-hour period of tourniquet ischemia on muscles in the rat hindlimb. The 2-hour ischemia was imposed without preconditioning, or was preceded by three brief (10 minutes on/10 minutes off) preischemic conditioning intervals. We compared muscle morphology, isometric contractile function, and muscle fatigue properties in predominantly fast-twitch, tibialis anterior muscles 3 (n = 8) and 7 (n = 8) days after ischemia-reperfusion. Two hours of ischemia, followed by reperfusion, results in a 20 percent reduction of muscle mass (p < 0.05) and a 33 percent reduction in tetanic tension (p < 0.05) when compared with controls (n = 8) at 3 days. The same protocol, when preceded by ischemic preconditioning, results in similar decreases in muscle mass and contractile function. Neuromuscular transmission was also impaired in both ischemic groups 7 days after ischemia. Nerve-evoked maximum tetanic tension was 69 percent of the tension produced by direct muscle stimulation in the ischemia group and 65 percent of direct tension in the ischemic preconditioning/ischemia group. In summary, ischemic preconditioning, using the same protocol reported to be effective in limiting infarct size in porcine muscle, had no significant benefit in limiting injury or improving recovery in the ischemic rat tibialis anterior. The value of ischemic preconditioning in reducing imposed ischemic-reperfusion-induced functional deficits in skeletal muscle remains to be demonstrated.

  9. Genetic Polymorphisms and Clopidogrel Efficacy for Acute Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis.

    PubMed

    Pan, Yuesong; Chen, Weiqi; Xu, Yun; Yi, Xingyang; Han, Yan; Yang, Qingwu; Li, Xin; Huang, Li'an; Johnston, S Claiborne; Zhao, Xingquan; Liu, Liping; Zhang, Qi; Wang, Guangyao; Wang, Yongjun; Wang, Yilong

    2017-01-03

    The association of genetic polymorphisms and clopidogrel efficacy in patients with ischemic stroke or transient ischemic attack (TIA) remains controversial. We performed a systematic review and meta-analysis to assess the association between genetic polymorphisms, especially CYP2C19 genotype, and clopidogrel efficacy for ischemic stroke or TIA. We conducted a comprehensive search of PubMed and EMBASE from their inceptions to June 24, 2016. Studies that reported clopidogrel-treated patients with stroke or TIA and with information on genetic polymorphisms were included. The end points were stroke, composite vascular events, and any bleeding. Among 15 studies of 4762 patients with stroke or TIA treated with clopidogrel, carriers of CYP2C19 loss-of-function alleles (*2, *3, and *8) were at increased risk of stroke in comparison with noncarriers (12.0% versus 5.8%; risk ratio, 1.92, 95% confidence interval, 1.57-2.35; P<0.001). Composite vascular events were also more frequent in carriers of CYP2C19 loss-of-function alleles than in noncarriers (13.7% versus 9.4%; risk ratio, 1.51, 95% confidence interval, 1.10-2.06; P=0.01), whereas bleeding rates were similar (2.4% versus 3.1%; risk ratio, 0.89, 95% confidence interval, 0.58-1.35; P=0.59). There was no evidence of statistical heterogeneity among the included studies for stroke, but there was for composite vascular events. Genetic variants other than CYP2C19 were not associated with clinical outcomes, with the exception that significant associations of PON1, P2Y12, and COX-1 with outcomes were observed in 1 study. Carriers of CYP2C19 loss-of-function alleles are at greater risk of stroke and composite vascular events than noncarriers among patients with ischemic stroke or TIA treated with clopidogrel. © 2016 American Heart Association, Inc.

  10. eNOS is required for acute in vivo ischemic preconditioning of the heart: effects of ischemic duration and sex

    PubMed Central

    Talukder, M. A. Hassan; Yang, Fuchun; Shimokawa, Hiroaki

    2010-01-01

    Ischemic preconditioning (IPC) is a powerful phenomenon that provides potent cardioprotection in mammalian hearts; however, the role of endothelial nitric oxide (NO) synthase (eNOS)-mediated NO in this process remains highly controversial. Questions also remain regarding this pathway as a function of sex and ischemic duration. Therefore, we performed extensive experiments in wild-type (WT) and eNOS knockout (eNOS−/−) mice to evaluate whether the infarct-limiting effect of IPC depends on eNOS, ischemic periods, and sex. Classical IPC was induced by three cycles of 5 min of regional coronary ischemia separated by 5 min of reperfusion and was followed by 30 or 60 min of sustained ischemia and 24 h of reperfusion. The control ischemia-reperfusion protocol had 30 or 60 min of ischemia followed by 24 h of reperfusion. Protection was evaluated by measuring the myocardial infarct size as a percentage of the area at risk. The major findings were that regardless of sex, WT mice exhibited robust IPC with significantly smaller myocardial infarction, whereas eNOS−/− mice did not. IPC-induced cardiac protection was absent in eNOS−/− mice of both Jackson and Harvard origin. In general, female WT mice had smaller infarctions compared with male WT mice. Although prolonged ischemia caused significantly larger infarctions in WT mice of both sexes, they were consistently protected by IPC. Importantly, prolonged myocardial ischemia was associated with increased mortality in eNOS−/− mice, and the survival rate was higher in female eNOS−/− mice compared with male eNOS−/− mice. In conclusion, IPC protects WT mice against in vivo myocardial ischemia-reperfusion injury regardless of sex and ischemic duration, but the deletion of eNOS abolishes the cardioprotective effect of classical IPC. PMID:20525875

  11. Ischemic preconditioning, retinal neuroprotection and histone deacetylase activities.

    PubMed

    Fan, Jie; Alsarraf, Oday; Chou, C James; Yates, Phillip W; Goodwin, Nicole C; Rice, Dennis S; Crosson, Craig E

    2016-05-01

    Increased histone deacetylase (HDAC) activity and the resulting dysregulation of protein acetylation is an integral event in retinal degenerations associated with ischemia and ocular hypertension. This study investigates the role of preconditioning on the process of acetylation in ischemic retinal injury. Rat eyes were unilaterally subjected to retinal injury by 45 min of acute ischemia, and retinal neuroprotection induced by 5 min of an ischemic preconditioning (IPC) event. HDAC activity was evaluated by a fluorometric enzymatic assay with selective isoform inhibitors. Retinal localization of acetylated histone-H3 was determined by immunohistochemistry on retina cross sections. Cleaved caspase-3 level was evaluated by Western blots. Electroretinogram (ERG) analyses were used to assess differences in retinal function seven days following ischemic injury. In control eyes, analysis of HDAC isoforms demonstrated that HDAC1/2 accounted for 28.4 ± 1.6%, HDAC3 for 42.4 ± 1.5% and HDAC6 activity 27.3 ± 3.5% of total activity. Following ischemia, total Class-I HDAC activity increased by 21.2 ± 6.2%, and this increase resulted solely from a rise in HDAC1/2 activity. No change in HDAC3 activity was measured. Activity of Class-II HDACs and HDAC8 was negligible. IPC stimulus prior to ischemic injury also suppressed the rise in Class-I HDAC activity, cleaved caspase-3 levels, and increased acetylated histone-H3 in the retina. In control animals 7 days post ischemia, ERG a- and b-wave amplitudes were significantly reduced by 34.9 ± 3.1% and 42.4 ± 6.3%, respectively. In rats receiving an IPC stimulus, the ischemia-induced decline in ERG a- and b-wave amplitudes was blocked. Although multiple HDACs were detected in the retina, these studies provide evidence that hypoacetylation associated with ischemic injury results from the selective rise in HDAC1/2 activity and that neuroprotection induced by IPC is mediated in part by suppressing HDAC activity. Copyright

  12. Endovascular vs medical management of acute ischemic stroke.

    PubMed

    Chen, Ching-Jen; Ding, Dale; Starke, Robert M; Mehndiratta, Prachi; Crowley, R Webster; Liu, Kenneth C; Southerland, Andrew M; Worrall, Bradford B

    2015-12-01

    To compare the outcomes between endovascular and medical management of acute ischemic stroke in recent randomized controlled trials (RCT). A systematic literature review was performed, and multicenter, prospective RCTs published from January 1, 2013, to May 1, 2015, directly comparing endovascular therapy to medical management for patients with acute ischemic stroke were included. Meta-analyses of modified Rankin Scale (mRS) and mortality at 90 days and symptomatic intracranial hemorrhage (sICH) for endovascular therapy and medical management were performed. Eight multicenter, prospective RCTs (Interventional Management of Stroke [IMS] III, Local Versus Systemic Thrombolysis for Acute Ischemic Stroke [SYNTHESIS] Expansion, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy [MR RESCUE], Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands [MR CLEAN], Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE], Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial [EXTEND-IA], Solitaire With the Intention For Thrombectomy as Primary Endovascular Treatment [SWIFT PRIME], and Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours [REVASCAT]) comprising 2,423 patients were included. Meta-analysis of pooled data demonstrated functional independence (mRS 0-2) at 90 days in favor of endovascular therapy (odds ratio [OR] = 1.71; p = 0.005). Subgroup analysis of the 6 trials with large vessel occlusion (LVO) criteria also demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.23; p < 0.00001). Subgroup analysis of the 5 trials that primarily utilized stent retriever devices (≥70%) in the intervention arm demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.39; p < 0.00001). No

  13. Endovascular vs medical management of acute ischemic stroke

    PubMed Central

    Ding, Dale; Starke, Robert M.; Mehndiratta, Prachi; Crowley, R. Webster; Liu, Kenneth C.; Southerland, Andrew M.; Worrall, Bradford B.

    2015-01-01

    Objective: To compare the outcomes between endovascular and medical management of acute ischemic stroke in recent randomized controlled trials (RCT). Methods: A systematic literature review was performed, and multicenter, prospective RCTs published from January 1, 2013, to May 1, 2015, directly comparing endovascular therapy to medical management for patients with acute ischemic stroke were included. Meta-analyses of modified Rankin Scale (mRS) and mortality at 90 days and symptomatic intracranial hemorrhage (sICH) for endovascular therapy and medical management were performed. Results: Eight multicenter, prospective RCTs (Interventional Management of Stroke [IMS] III, Local Versus Systemic Thrombolysis for Acute Ischemic Stroke [SYNTHESIS] Expansion, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy [MR RESCUE], Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands [MR CLEAN], Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE], Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial [EXTEND-IA], Solitaire With the Intention For Thrombectomy as Primary Endovascular Treatment [SWIFT PRIME], and Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours [REVASCAT]) comprising 2,423 patients were included. Meta-analysis of pooled data demonstrated functional independence (mRS 0–2) at 90 days in favor of endovascular therapy (odds ratio [OR] = 1.71; p = 0.005). Subgroup analysis of the 6 trials with large vessel occlusion (LVO) criteria also demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.23; p < 0.00001). Subgroup analysis of the 5 trials that primarily utilized stent retriever devices (≥70%) in the intervention arm demonstrated functional independence at 90 days in favor of endovascular therapy

  14. Extracorporeal shock wave therapy for ischemic cardiovascular disorders.

    PubMed

    Ito, Kenta; Fukumoto, Yoshihiro; Shimokawa, Hiroaki

    2011-10-01

    Ischemic heart disease is the leading cause of death and a major cause of hospital admissions, with the number of affected patients increasing worldwide. The current management of ischemic heart disease has three major therapeutic options: medication, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). However, the prognosis for patients with severe ischemic heart disease without indications for PCI or CABG still remains poor due to the lack of effective treatments. It is therefore crucial to develop alternative therapeutic strategies for severe ischemic heart disease. Extracorporeal shock wave (SW) therapy was introduced clinically more than 20 years ago to fragment kidney stones, which has markedly improved the treatment of urolithiasis. We found that a low-energy SW (about 10% of the energy density used for urolithiasis) effectively increases the expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. Based on this in vitro study, we initiated in vivo studies and have demonstrated that extracorporeal cardiac SW therapy with a low-energy SW up-regulates the expression of VEGF, induces neovascularization, and improves myocardial ischemia in a porcine model of chronic myocardial ischemia, without any adverse effects in vivo. On the basis of promising results in animal studies, we performed a series of clinical studies in patients with severe coronary artery disease without indication for PCI or CABG, including, firstly, an open trial followed by a placebo-controlled, double-blind study. In both studies, our extracorporeal cardiac SW therapy improved symptoms, exercise capacity, and myocardial perfusion in patients with severe coronary artery disease. Importantly, no procedural complications or adverse effects were noted. The SW therapy was also effective in ameliorating left ventricular remodeling after acute myocardial infarction (MI) in pigs and in enhancing angiogenesis in hind-limb ischemia in

  15. Effect of hyperthermia on prognosis after acute ischemic stroke.

    PubMed

    Saini, Monica; Saqqur, Maher; Kamruzzaman, Anmmd; Lees, Kennedy R; Shuaib, Ashfaq

    2009-09-01

    Experimental studies have shown that hyperthermia is a determinant of poor outcome after ischemic stroke. Clinical studies evaluating the effect of temperature on poststroke outcome have, however, been limited by small sample sizes. We sought to evaluate the effect of temperature and timing of hyperthermia on outcome after ischemic stroke. Data of 5305 patients in acute stroke trials from the Virtual International Stroke Trials Archive (VISTA) data set were analyzed. Data for temperatures at baseline, eighth, 24th, 48th, and 72nd hours, and seventh day were assessed in relation to outcome (poor versus good) based on the modified Rankin Scale at 3 months. Hyperthermia was defined as temperature >37.2 degrees C and poor outcome as 90-day modified Rankin Scale >2. Hazard ratios with 95% CIs were reported for hyperthermia in relation to the outcome. Logistic regression models, in relation to hyperthermia, were fitted for a set of preselected covariates at different time points to identify predictors/determinants of hyperthermia. The average age of patients was 68.0+/-11.9 years, 2380 (44.9%) were females, and 42.3% (2233) received thrombolysis using recombinant tissue plasminogen activator. After adjustment, hyperthermia was a statistically significant predictor of poor outcome. The hazard ratios (95% CI) for poor outcome in relation to hyperthermia at different time points were: baseline 1.2 (1.0 to 1.4), eighth hour 1.7 (1.2 to 2.2), 24th hour 1.5 (1.2 to 1.9), 48th hour 2.0 (1.5 to 2.6), 72nd hour 2.2 (1.7 to 2.9), and seventh day 2.7 (2.0 to 3.8). Gender, stroke severity (National Institutes of Health Stroke Scale score >16), white blood cell count, and antibiotic use were significantly associated with hyperthermia (P< or =0.01). Hyperthermia, in acute ischemic stroke, is associated with a poor clinical outcome. The later the hyperthermia occurs within the first week, the worse the prognosis. Severity of stroke and inflammation are important determinants of

  16. Defective neuropeptide processing and ischemic brain injury: a study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains

    PubMed Central

    Zhan, Shuqin; Zhao, Hongbo; White, Aaron J; Minami, Manabu; Pignataro, Giuseppe; Yang, Tao; Zhu, Xiaorong; Lan, Jingquan; Xiong, Zhigang; Steiner, Donald F; Simon, Roger P; Zhou, An

    2010-01-01

    Using a focal cerebral ischemia model in rats, brain ischemia-induced changes in expression levels of mRNA and protein, and activities of proprotein convertase 2 (PC2) in the cortex were examined. In situ hybridization analyses revealed a transient upregulation of the mRNA level for PC2 at an early reperfusion hour, at which the level of PC2 protein was also high as determined by immunocytochemistry and western blotting. When enzymatic activities of PC2 were analyzed using a synthetic substrate, a significant decrease was observed at early reperfusion hours at which levels of PC2 protein were still high. Also decreased at these reperfusion hours were tissue levels of dynorphin-A(1–8) (DYN-A(1–8)), a PC2 substrate, as determined by radioimmunoassay. Further examination of PC2 protein biosynthesis by metabolic labeling in cultured neuronal cells showed that in ischemic cells, the proteolytic processing of PC2 was greatly attenuated. Finally, in mice, an intracerebroventricular administration of synthetic DYN-A(1–8) significantly reduced the extent of ischemic brain injury. In mice those lack an active PC2, exacerbated brain injury was observed after an otherwise non-lethal focal ischemia. We conclude that brain ischemia attenuates PC2 and PC2-mediated neuropeptide processing. This attenuation may play a role in the pathology of ischemic brain injury. PMID:19142196

  17. Perception of Recurrent Stroke Risk among Black, White and Hispanic Ischemic Stroke and Transient Ischemic Attack Survivors: The SWIFT Study

    PubMed Central

    Boden-Albala, Bernadette; Carman, Heather; Moran, Megan; Doyle, Margaret; Paik, Myunghee C.

    2011-01-01

    Objectives Risk modification through behavior change is critical for primary and secondary stroke prevention. Theories of health behavior identify perceived risk as an important component to facilitate behavior change; however, little is known about perceived risk of vascular events among stroke survivors. Methods The SWIFT (Stroke Warning Information and Faster Treatment) study includes a prospective population-based ethnically diverse cohort of ischemic stroke and transient ischemic attack survivors. We investigate the baseline relationship between demographics, health beliefs, and knowledge on risk perception. Regression models examined predictors of inaccurate perception. Results Only 20% accurately estimated risk, 10% of the participants underestimated risk, and 70% of the 817 study participants significantly overestimated their risk for a recurrent stroke. The mean perceived likelihood of recurrent ischemic stroke in the next 10 years was 51 ± 7%. We found no significant differences by race-ethnicity with regard to accurate estimation of risk. Inaccurate estimation of risk was associated with attitudes and beliefs [worry (p < 0.04), fatalism (p < 0.07)] and memory problems (p < 0.01), but not history or knowledge of vascular risk factors. Conclusion This paper provides a unique perspective on how factors such as belief systems influence risk perception in a diverse population at high stroke risk. There is a need for future research on how risk perception can inform primary and secondary stroke prevention. Copyright © 2011 S. Karger AG, Basel PMID:21894045

  18. Perception of recurrent stroke risk among black, white and Hispanic ischemic stroke and transient ischemic attack survivors: the SWIFT study.

    PubMed

    Boden-Albala, Bernadette; Carman, Heather; Moran, Megan; Doyle, Margaret; Paik, Myunghee C

    2011-01-01

    Risk modification through behavior change is critical for primary and secondary stroke prevention. Theories of health behavior identify perceived risk as an important component to facilitate behavior change; however, little is known about perceived risk of vascular events among stroke survivors. The SWIFT (Stroke Warning Information and Faster Treatment) study includes a prospective population-based ethnically diverse cohort of ischemic stroke and transient ischemic attack survivors. We investigate the baseline relationship between demographics, health beliefs, and knowledge on risk perception. Regression models examined predictors of inaccurate perception. Only 20% accurately estimated risk, 10% of the participants underestimated risk, and 70% of the 817 study participants significantly overestimated their risk for a recurrent stroke. The mean perceived likelihood of recurrent ischemic stroke in the next 10 years was 51 ± 7%. We found no significant differences by race-ethnicity with regard to accurate estimation of risk. Inaccurate estimation of risk was associated with attitudes and beliefs [worry (p < 0.04), fatalism (p < 0.07)] and memory problems (p < 0.01), but not history or knowledge of vascular risk factors. This paper provides a unique perspective on how factors such as belief systems influence risk perception in a diverse population at high stroke risk. There is a need for future research on how risk perception can inform primary and secondary stroke prevention. Copyright © 2011 S. Karger AG, Basel.

  19. Persistence of secondary prevention medication and related factors for acute ischemic stroke and transient ischemic attack in China.

    PubMed

    Jiang, Yue; Yang, Xiaomeng; Li, Zixiao; Pan, Yuesong; Wang, Yilong; Wang, Yongjun; Ji, Ruijun; Wang, Chen

    2017-06-01

    We recently measured the longitudinal use of secondary prevention medication following hospital discharge and the factors influencing persistence in patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA) in China. Patients with AIS and TIA who were enrolled in the China National Stroke Registry II from June 2012 to January 2013 were surveyed to determine persistence. The medications included antiplatelet therapies, warfarin, antihypertensive therapies, statins, and diabetes medications. We determined persistence for a three-month period following discharge. Persistence was defined as the continuation of all secondary preventive medications prescribed upon hospital discharge. The factors associated with medication persistence 3 months after discharge were examined using a multivariable logistic regression. Of the 21,592 patients with AIS and TIA, 18,344 (91.2%) were eligible for analysis. After 3 months post-discharge, 46.2% of the subjects continued to take all secondary prevention medications prescribed at discharge. Independent predictors of three-month medication persistence included younger age, absence of a history of diabetes or atrial fibrillation, higher family income, less severe stroke, index cerebrovascular event of ischemic stroke, and being treated in a hospital with a stroke unit and more beds in the neurology department. More than half of patients with AIS and TIA reported discontinuing one or more secondary prevention medications within 3 months of hospital discharge. Several factors associated with medication persistence were identified. Here, we propose strategies that could be implemented to improve the quality of secondary prevention.

  20. Ischemic compression after trigger point injection affect the treatment of myofascial trigger points.

    PubMed

    Kim, Soo A; Oh, Ki Young; Choi, Won Hyuck; Kim, In Kyum

    2013-08-01

    To investigate the effects of trigger point injection with or without ischemic compression in treatment of myofascial trigger points in the upper trapezius muscle. SIXTY PATIENTS WITH ACTIVE MYOFASCIAL TRIGGER POINTS IN UPPER TRAPEZIUS MUSCLE WERE RANDOMLY DIVIDED INTO THREE GROUPS: group 1 (n=20) received only trigger point injections, group 2 (n=20) received trigger point injections with 30 seconds of ischemic compression, and group 3 (n=20) received trigger point injections with 60 seconds of ischemic compression. The visual analogue scale, pressure pain threshold, and range of motion of the neck were assessed before treatment, immediately after treatment, and 1 week after treatment. Korean Neck Disability Indexes were assessed before treatment and 1 week after treatment. We found a significant improvement in all assessment parameters (p<0.05) in all groups. But, receiving trigger point injections with ischemic compression group showed significant improvement as compared with the receiving only trigger point injections group. And no significant differences between receiving 30 seconds of ischemic compression group and 60 seconds of ischemic compression group. This study demonstrated the effectiveness of ischemic compression for myofascial trigger point. Trigger point injections combined with ischemic compression shows better effects on treatment of myofascial trigger points in the upper trapezius muscle than the only trigger point injections therapy. But the duration of ischemic compression did not affect treatment of myofascial trigger point.

  1. Neural stem cell transplantation in ischemic stroke: A role for preconditioning and cellular engineering.

    PubMed

    Bernstock, Joshua D; Peruzzotti-Jametti, Luca; Ye, Daniel; Gessler, Florian A; Maric, Dragan; Vicario, Nunzio; Lee, Yang-Ja; Pluchino, Stefano; Hallenbeck, John M

    2017-07-01

    Ischemic stroke continues to be a leading cause of morbidity and mortality throughout the world. To protect and/or repair the ischemic brain, a multitiered approach may be centered on neural stem cell (NSC) transplantation. Transplanted NSCs exert beneficial effects not only via structural replacement, but also via immunomodulatory and/or neurotrophic actions. Unfortunately, the clinical translation of such promising therapies remains elusive, in part due to their limited persistence/survivability within the hostile ischemic microenvironment. Herein, we discuss current approaches for the development of NSCs more amenable to survival within the ischemic brain as a tool for future cellular therapies in stroke.

  2. Ischemic colitis as a manifestation of thrombotic microangiopathy following bone marrow transplantation.

    PubMed

    Komeno, Yukiko; Ogawa, Seishi; Ishida, Tateru; Takeuchi, Kengo; Tsujino, Shiho; Kurokawa, Mineo; Aoki, Katsunori; Kanda, Yoshinobu; Chiba, Shigeru; Motokura, Toru; Fukayama, Masashi; Hirai, Hisamaru

    2003-12-01

    Thrombotic microangiopathy (TMA) is a microvascular disorder characterized by platelet aggregation and hemolytic anemia. In the setting of bone marrow transplantation (BMT), ischemic colitis due to TMA is difficult to differentiate from acute graft-versus-host disease. We report a 32-year-old man who presented ischemic colitis due to TMA after unrelated BMT for myelodysplastic syndrome. He suffered from treatment-resistant bloody diarrhea, and died of renal failure and Aspergillus pleuritis on day 253 post-BMT. Autopsy revealed endothelial injuries of arterioles and ischemic changes in the intestines and kidneys. Clinical and pathological characteristics of ischemic colitis due to BMT-associated TMA are described.

  3. Renal dysfunction and chronic kidney disease in ischemic stroke and transient ischemic attack: A population-based study.

    PubMed

    Hayden, Derek; McCarthy, Christine; Akijian, Layan; Callaly, Elizabeth; Ní Chróinín, Danielle; Horgan, Gillian; Kyne, Lorraine; Duggan, Joseph; Dolan, Eamon; O' Rourke, Killian; Williams, David; Murphy, Sean; O'Meara, Yvonne; Kelly, Peter J

    2017-10-01

    Background and purpose The prevalence of chronic kidney disease (estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m(2) for ≥3 months, chronic kidney disease (CKD)) in ischemic stroke and transient ischemic attack (TIA) is unknown, as estimates have been based on single-point estimates of renal function. Studies investigating the effect of renal dysfunction (eGFR < 60 mL/min per 1.73 m(2), renal dysfunction) on post-stroke outcomes are limited to hospitalized cohorts and have provided conflicting results. Methods We investigated rates, determinants and outcomes of renal dysfunction in ischemic stroke and TIA in the North Dublin Population Stroke Study. We also investigate the persistence of renal dysfunction in 90-day survivors to determine the prevalence of CKD. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using Kaplan-Meier survival curves and Cox proportional hazards modeling. Results In 547 patients (ischemic stroke in 76.4%, TIA in 23.6%), the mean eGFR at presentation was 63.7 mL/min/1.73 m(2) (SD 22.1). Renal dysfunction was observed in 44.6% (244/547). Among 90-day survivors, 31.2% (139/446) met criteria for CKD. After adjusting for age and stroke severity, eGFR < 45 mL/min/1.73 m(2) (hazard ratio 2.53, p = 0.01) independently predicted 28-day fatality but not at two years. Poor post-stroke functional outcome (Modified Rankin Scale 3-5) at two years was more common in those with renal dysfunction (52.5% vs. 20.6%, p < 0.001). After adjusting for age, stroke severity and pre-stroke disability, renal dysfunction (OR 2.17, p = 0.04) predicted poor functional outcome. Conclusion Renal dysfunction and CKD are common in ischemic stroke and TIA. Renal dysfunction is associated with considerable post-stroke morbidity and mortality. Further studies are needed to investigate if modifiable mechanisms underlie these associations.

  4. Effect of Extended CT Perfusion Acquisition Time on Ischemic Core and Penumbra Volume Estimation in Patients with Acute Ischemic Stroke due to a Large Vessel Occlusion

    PubMed Central

    Borst, Jordi; Marquering, Henk A.; Beenen, Ludo F. M.; Berkhemer, Olvert A.; Dankbaar, Jan Willem; Riordan, Alan J.; Majoie, Charles B. L. M.

    2015-01-01

    Background and Purpose It has been suggested that CT Perfusion acquisition times <60 seconds are too short to capture the complete in and out-wash of contrast in the tissue, resulting in incomplete time attenuation curves. Yet, these short acquisitions times are not uncommon in clinical practice. The purpose of this study was to investigate the occurrence of time attenuation curve truncation in 48 seconds CT Perfusion acquisition and to quantify its effect on ischemic core and penumbra estimation in patients with acute ischemic stroke due to a proximal intracranial arterial occlusion of the anterior circulation. Materials and Methods We analyzed CT Perfusion data with 48 seconds and extended acquisition times, assuring full time attenuation curves, of 36 patients. Time attenuation curves were classified as complete or truncated. Ischemic core and penumbra volumes resulting from both data sets were compared by median paired differences and interquartile ranges. Controlled experiments were performed using a digital CT Perfusion phantom to investigate the effect of time attenuation curve truncation on ischemic core and penumbra estimation. Results In 48 seconds acquisition data, truncation was observed in 24 (67%) cases for the time attenuation curves in the ischemic core, in 2 cases for the arterial input function and in 5 cases for the venous output function. Analysis of extended data resulted in smaller ischemic cores and larger penumbras with a median difference of 13.2 (IQR: 4.3–26.0)ml (P<0.001) and; 12.4 (IQR: 4.1–25.7)ml (P<0.001), respectively. The phantom data showed increasing ischemic core overestimation with increasing tissue time attenuation curve truncation. Conclusions Truncation is common in patients with large vessel occlusion and results in repartitioning of the area of hypoperfusion into larger ischemic core and smaller penumbra estimations. Phantom experiments confirmed that truncation results in overestimation of the ischemic core. PMID

  5. Quality of Care and Ischemic Stroke Risk After Hospitalization for Transient Ischemic Attack: Findings From Get With The Guidelines-Stroke.

    PubMed

    O'Brien, Emily C; Zhao, Xin; Fonarow, Gregg C; Schulte, Phillip J; Dai, David; Smith, Eric E; Schwamm, Lee H; Bhatt, Deepak L; Xian, Ying; Saver, Jeffrey L; Reeves, Mathew J; Peterson, Eric D; Hernandez, Adrian F

    2015-10-01

    Patients with transient ischemic attack (TIA) are at increased risk for ischemic stroke. We derived a prediction rule for 1-year ischemic stroke risk post-TIA, examining estimated risk, receipt of inpatient quality of care measures for TIA, and the presence or absence of stroke at 1 year post discharge. We linked 67 892 TIA Get With The Guidelines-Stroke patients >65 years (2003-2008) to Medicare inpatient claims to obtain longitudinal outcomes. Using Cox proportional hazards modeling in a split sample, we identified baseline demographics and clinical characteristics associated with ischemic stroke admission during the year post-TIA, and developed a Get With The Guidelines Ischemic Stroke after TIA Risk Score; performance was examined in the validation sample. Quality of care was estimated by a global defect-free care measure, and individual performance measures within estimated risk score quintiles. The overall hospital admission rate for ischemic stroke during the year post-TIA was 5.7%. Patients with ischemic stroke were more likely to be older, black, and have higher rates of smoking, previous stroke, diabetes mellitus, previous myocardial infarction, heart failure, and atrial fibrillation. The Risk Score showed moderate discriminative performance (c-statistic=0.606); highest quintile patients were less likely to receive statins, smoking cessation counseling, and defect-free care. Although not associated with 1-year ischemic stroke, DCF was associated with a significantly lower risk of all-cause mortality. TIA patients with high estimated ischemic stroke risk are less likely to receive defect-free care than low-risk patients. Standardized risk assessment and delivery of optimal inpatient care are needed to reduce this risk-treatment mismatch. © 2015 American Heart Association, Inc.

  6. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Geeganage, Chamila M; Diener, Hans-Christoph; Algra, Ale; Chen, Christopher; Topol, Eric J; Dengler, Reinhard; Markus, Hugh S; Bath, Matthew W; Bath, Philip M W

    2012-04-01

    Antiplatelets are recommended for patients with acute noncardioembolic stroke or transient ischemic attack. We compared the safety and efficacy of dual versus mono antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack. Completed randomized controlled trials of dual versus mono antiplatelet therapy in patients with acute (≤3 days) ischemic stroke/transient ischemic attack were identified using electronic bibliographic searches. The primary outcome was recurrent stroke (ischemic, hemorrhagic, unknown; fatal, nonfatal). Comparison of binary outcomes between treatment groups was analyzed with random effect models and described using risk ratios (95% CI). Twelve completed randomized trials involving 3766 patients were included. In comparison with mono antiplatelet therapy, dual therapy (aspirin+dipyridamole and aspirin+clopidogrel) significantly reduced stroke recurrence, dual 58 (3.3%) versus mono 91 (5.0%; risk ratio, 0.67; 95% CI, 0.49-0.93); composite vascular event (stroke, myocardial infarction, vascular death), dual 74 (4.4%) versus mono 106 (6%; risk ratio, 0.75; 95% CI, 0.56-0.99); and the combination of stroke, transient ischemic attack, acute coronary syndrome, and all death, dual 100 (1.7%) versus mono 136 (9.1%; risk ratio, 0.71; 95% CI, 0.56-0.91); dual therapy was also associated with a nonsignificant trend to increase major bleeding, dual 15 (0.9%) versus mono 6 (0.4%; risk ratio, 2.09; 95% CI, 0.86-5.06). Dual antiplatelet therapy appears to be safe and effective in reducing stroke recurrence and combined vascular events in patients with acute ischemic stroke or transient ischemic attack as compared with mono therapy. These results need to be tested in prospective studies.

  7. Acute ischemic preconditioning of skeletal muscle prior to flap elevation augments muscle-flap survival.

    PubMed

    Carroll, C M; Carroll, S M; Overgoor, M L; Tobin, G; Barker, J H

    1997-07-01

    Ischemic preconditioning of the myocardium with repeated brief periods of ischemia and reperfusion prior to prolonged ischemia significantly reduces subsequent myocardial infarction. Following ischemic preconditioning, two "windows of opportunity" (early and late) exist, during which time prolonged ischemia can occur with reduced infarction size. The early window occurs at approximately 4 hours and the late window at 24 hours following ischemic preconditioning of the myocardium. We investigated if ischemic preconditioning of skeletal muscle prior to flap creation improved subsequent flap survival and perfusion immediately or 24 hours following ischemic preconditioning. Currently, no data exist on the utilization of ischemic preconditioning in this fashion. The animal model used was the latissimus dorsi muscle of adult male Sprague-Dawley rats. Animals were assigned to three groups, and the right or left latissimus dorsi muscle was chosen randomly in each animal. Group 1 (n = 12) was the control group, in which the entire latissimus dorsi muscle was elevated acutely without ischemic preconditioning. Group 2 (n = 8) investigated the effects of ischemic preconditioning in the early window. In this group, the latissimus dorsi muscle was elevated immediately following preconditioning. Group 3 (n = 8) investigated the effects of ischemic preconditioning in the late window, with elevation of the latissimus dorsi muscle 24 hours following ischemic preconditioning. The preconditioning regimen used in groups 2 and 3 was two 30-minute episodes of normothermic global ischemia with intervening 10-minute episodes of reperfusion. Latissimus dorsi muscle ischemia was created by occlusion of the thoracodorsal artery and vein and the intercostal perforators, after isolation of the muscle on these vessels. Muscle perfusion was assessed by a laser-Doppler perfusion imager. One week after flap elevation, muscle necrosis was quantified in all groups by means of computer-assisted digital

  8. Apolipoprotein A-I and Paraoxonase-1 Are Potential Blood Biomarkers for Ischemic Stroke Diagnosis.

    PubMed

    Walsh, Kyle B; Hart, Kimberly; Roll, Susan; Sperling, Matthew; Unruh, Dusten; Davidson, W Sean; Lindsell, Christopher J; Adeoye, Opeolu

    2016-06-01

    Blood biomarkers for ischemic and hemorrhagic stroke diagnosis remain elusive. Recent investigations suggested that apolipoprotein (Apo), matrix metalloproteinase (MMP), and paraoxonase-1 may be associated with stroke. We hypothesized that Apo A-I, Apo C-I, Apo C-III, MMP-3, MMP-9, and paraoxonase-1 are differentially expressed in ischemic stroke, hemorrhagic stroke, and controls. In a single-center prospective observational study, consecutive stroke cases were enrolled if blood samples were obtainable within 12 hours of symptom onset. Age- (±5 years), race-, and sex-matched controls were recruited. Multiplex assays were used to measure protein levels. The Wilcoxon signed-rank test and the Mann-Whitney U-test were used to compare biomarker values between ischemic stroke patients and controls, hemorrhagic stroke patients and controls, and ischemic and hemorrhagic stroke patients. The 95% confidence intervals (CIs) for the difference of 2 medians were calculated. Fourteen ischemic stroke case-control pairs and 23 intracerebral hemorrhage (ICH) case-control pairs were enrolled. Median Apo A-I levels were lower in ischemic stroke cases versus controls (140 mg/dL versus 175 mg/dL, difference of 35 mg/dL, 95% CI -54 to -16) and in ischemic stroke versus ICH cases (140 mg/dL versus 180 mg/dL, difference of 40 mg/dL, 95% CI -57 to -23). Median paraoxonase-1 was lower in ischemic stroke cases than in both ICH cases and matched controls. Median Apo C-I was slightly lower in ischemic stroke cases than in ICH cases. There were no differences between groups for MMP-3, MMP-9, and Apo C-III. Apo A-I and paraoxonase-1 levels may be clinically useful for ischemic stroke diagnosis and for differentiating between ischemic and hemorrhagic strokes. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  9. Coenzyme Q10 ameliorates oxidative stress and prevents mitochondrial alteration in ischemic retinal injury.

    PubMed

    Lee, Dongwook; Kim, Keun-Young; Shim, Myoung Sup; Kim, Sang Yeop; Ellisman, Mark H; Weinreb, Robert N; Ju, Won-Kyu

    2014-04-01

    Coenzyme Q10 (CoQ10) acts by scavenging reactive oxygen species for protecting neuronal cells against oxidative stress in neurodegenerative diseases. We tested whether a diet supplemented with CoQ10 ameliorates oxidative stress and mitochondrial alteration, as well as promotes retinal ganglion cell (RGC) survival in ischemic retina induced by intraocular pressure elevation. A CoQ10 significantly promoted RGC survival at 2 weeks after ischemia. Superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) expression were significantly increased at 12 h after ischemic injury. In contrast, the CoQ10 significantly prevented the upregulation of SOD2 and HO-1 protein expression in ischemic retina. In addition, the CoQ10 significantly blocked activation of astroglial and microglial cells in ischemic retina. Interestingly, the CoQ10 blocked apoptosis by decreasing caspase-3 protein expression in ischemic retina. Bax and phosphorylated Bad (pBad) protein expression were significantly increased in ischemic retina at 12 h. Interestingly, while CoQ10 significantly decreased Bax protein expression in ischemic retina, CoQ10 showed greater increase of pBad protein expression. Of interest, ischemic injury significantly increased mitochondrial transcription factor A (Tfam) protein expression in the retina at 12 h, however, CoQ10 significantly preserved Tfam protein expression in ischemic retina. Interestingly, there were no differences in mitochondrial DNA content among control- or CoQ10-treated groups. Our findings demonstrate that CoQ10 protects RGCs against oxidative stress by modulating the Bax/Bad-mediated mitochondrial apoptotic pathway as well as prevents mitochondrial alteration by preserving Tfam protein expression in ischemic retina. Our results suggest that CoQ10 may provide neuroprotection against oxidative stress-mediated mitochondrial alterations in ischemic retinal injury.

  10. Chronic nicotine exposure exacerbates acute renal ischemic injury

    PubMed Central

    Grifoni, Samira; Clark, Jeb S.; Csongradi, Eva; Maric, Christine; Juncos, Luis A.

    2011-01-01

    Recent epidemiological reports showed that smoking has a negative impact on renal function and elevates the renal risk not only in the renal patient but perhaps also in the healthy population. Studies suggested that nicotine, a major tobacco alkaloid, links smoking to renal dysfunction. While several studies showed that smoking/chronic nicotine exposure exacerbates the progression of chronic renal diseases, its impact on acute kidney injury is virtually unknown. Here, we studied the effects of chronic nicotine exposure on acute renal ischemic injury. We found that chronic nicotine exposure increased the extent of renal injury induced by warm ischemia-reperfusion as evidenced by morphological changes, increase in plasma creatinine level, and kidney injury molecule-1 expression. We also found that chronic nicotine exposure elevated markers of oxidative stress such as nitrotyrosine as well as malondialdehyde. Interestingly, chronic nicotine exposure alone increased oxidative stress and injury in the kidney without morphological alterations. Chronic nicotine treatment not only increased reactive oxygen species (ROS) production and injury but also exacerbated oxidative stress-induced ROS generation through NADPH oxidase and mitochondria in cultured renal proximal tubule cells. The resultant oxidative stress provoked injury through JNK-mediated activation of the activator protein (AP)-1 transcription factor in vitro. This mechanism might exist in vivo as phosphorylation of JNK and its downstream target c-jun, a component of the AP-1 transcription factor, is elevated in the ischemic kidneys exposed to chronic nicotine. Our results imply that smoking may sensitize the kidney to ischemic insults and perhaps facilitates progression of acute kidney injury to chronic kidney injury. PMID:21511693

  11. Hepcidin Is Involved in Iron Regulation in the Ischemic Brain

    PubMed Central

    Shi, Honglian; Zhao, Ya-Shuo; Chang, Shi-Yang; Yu, Peng; Wu, Wen-Shuang; Zhao, Chen-Yang; Chang, Yan-Zhong; Duan, Xiang-Lin

    2011-01-01

    Oxidative stress plays an important role in neuronal injuries caused by cerebral ischemia. It is well established that free iron increases significantly during ischemia and is responsible for oxidative damage in the brain. However, the mechanism of this ischemia-induced increase in iron is not completely understood. In this report, the middle cerebral artery occlusion (MCAO) rat model was performed and the mechanism of iron accumulation in cerebral ischemia-reperfusion was studied. The expression of L-ferritin was significantly increased in the cerebral cortex, hippocampus, and striatum on the ischemic side, whereas H-ferritin was reduced in the striatum and increased in the cerebral cortex and hippocampus. The expression level of the iron-export protein ferroportin1 (FPN1) significantly decreased, while the expression of transferrin receptor 1 (TfR1) was increased. In order to elucidate the mechanisms of FPN1 regulation, we studied the expression of the key regulator of FPN1, hepcidin. We observed that the hepcidin level was significantly elevated in the ischemic side of the brain. Knockdown hepcidin repressed the increasing of L-ferritin and decreasing of FPN1 invoked by ischemia-reperfusion. The results indicate that hepcidin is an important contributor to iron overload in cerebral ischemia. Furthermore, our results demonstrated that the levels of hypoxia-inducible factor-1α (HIF-1α) were significantly higher in the cerebral cortex, hippocampus and striatum on the ischemic side; therefore, the HIF-1α-mediated TfR1 expression may be another contributor to the iron overload in the ischemia-reperfusion brain. PMID:21957487

  12. Sex Stratified Neuronal Cultures to Study Ischemic Cell Death Pathways

    PubMed Central

    Verma, Saurabh; Traystman, Richard J.; Herson, Paco S.

    2013-01-01

    Sex differences in neuronal susceptibility to ischemic injury and neurodegenerative disease have long been observed, but the signaling mechanisms responsible for those differences remain unclear. Primary disassociated embryonic neuronal culture provides a simplified experimental model with which to investigate the neuronal cell signaling involved in cell death as a result of ischemia or disease; however, most neuronal cultures used in research today are mixed sex. Researchers can and do test the effects of sex steroid treatment in mixed sex neuronal cultures in models of neuronal injury and disease, but accumulating evidence suggests that the female brain responds to androgens, estrogens, and progesterone differently than the male brain. Furthermore, neonate male and female rodents respond differently to ischemic injury, with males experiencing greater injury following cerebral ischemia than females. Thus, mixed sex neuronal cultures might obscure and confound the experimental results; important information might be missed. For this reason, the Herson Lab at the University of Colorado School of Medicine routinely prepares sex-stratified primary disassociated embryonic neuronal cultures from both hippocampus and cortex. Embryos are sexed before harvesting of brain tissue and male and female tissue are disassociated separately, plated separately, and maintained separately. Using this method, the Herson Lab has demonstrated a male-specific role for the ion channel TRPM2 in ischemic cell death. In this manuscript, we share and discuss our protocol for sexing embryonic mice and preparing sex-stratified hippocampal primary disassociated neuron cultures. This method can be adapted to prepare sex-stratified cortical cultures and the method for embryo sexing can be used in conjunction with other protocols for any study in which sex is thought to be an important determinant of outcome. PMID:24378980

  13. Sex stratified neuronal cultures to study ischemic cell death pathways.

    PubMed

    Fairbanks, Stacy L; Vest, Rebekah; Verma, Saurabh; Traystman, Richard J; Herson, Paco S

    2013-12-09

    Sex differences in neuronal susceptibility to ischemic injury and neurodegenerative disease have long been observed, but the signaling mechanisms responsible for those differences remain unclear. Primary disassociated embryonic neuronal culture provides a simplified experimental model with which to investigate the neuronal cell signaling involved in cell death as a result of ischemia or disease; however, most neuronal cultures used in research today are mixed sex. Researchers can and do test the effects of sex steroid treatment in mixed sex neuronal cultures in models of neuronal injury and disease, but accumulating evidence suggests that the female brain responds to androgens, estrogens, and progesterone differently than the male brain. Furthermore, neonate male and female rodents respond differently to ischemic injury, with males experiencing greater injury following cerebral ischemia than females. Thus, mixed sex neuronal cultures might obscure and confound the experimental results; important information might be missed. For this reason, the Herson Lab at the University of Colorado School of Medicine routinely prepares sex-stratified primary disassociated embryonic neuronal cultures from both hippocampus and cortex. Embryos are sexed before harvesting of brain tissue and male and female tissue are disassociated separately, plated separately, and maintained separately. Using this method, the Herson Lab has demonstrated a male-specific role for the ion channel TRPM2 in ischemic cell death. In this manuscript, we share and discuss our protocol for sexing embryonic mice and preparing sex-stratified hippocampal primary disassociated neuron cultures. This method can be adapted to prepare sex-stratified cortical cultures and the method for embryo sexing can be used in conjunction with other protocols for any study in which sex is thought to be an important determinant of outcome.

  14. Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection

    PubMed Central

    Cowan, Douglas B.; Yao, Rouan; Akurathi, Vamsidhar; Snay, Erin R.; Thedsanamoorthy, Jerusha K.; Zurakowski, David; Ericsson, Maria; Friehs, Ingeborg; Wu, Yaotang; Levitsky, Sidney; del Nido, Pedro J.; Packard, Alan B.

    2016-01-01

    We have previously shown that transplantation of autologously derived, respiration-competent mitochondria by direct injection into the heart following transient ischemia and reperfusion enhances cell viability and contractile function. To increase the therapeutic potential of this approach, we investigated whether exogenous mitochondria can be effectively delivered through the coronary vasculature to protect the ischemic myocardium and studied the fate of these transplanted organelles in the heart. Langendorff-perfused rabbit hearts were subjected to 30 minutes of ischemia and then reperfused for 10 minutes. Mitochondria were labeled with 18F-rhodamine 6G and iron oxide nanoparticles. The labeled mitochondria were either directly injected into the ischemic region or delivered by vascular perfusion through the coronary arteries at the onset of reperfusion. These hearts were used for positron emission tomography, microcomputed tomography, and magnetic resonance imaging with subsequent microscopic analyses of tissue sections to confirm the uptake and distribution of exogenous mitochondria. Injected mitochondria were localized near the site of delivery; while, vascular perfusion of mitochondria resulted in rapid and extensive dispersal throughout the heart. Both injected and perfused mitochondria were observed in interstitial spaces and were associated with blood vessels and cardiomyocytes. To determine the efficacy of vascular perfusion of mitochondria, an additional group of rabbit hearts were subjected to 30 minutes of regional ischemia and reperfused for 120 minutes. Immediately following regional ischemia, the hearts received unlabeled, autologous mitochondria delivered through the coronary arteries. Autologous mitochondria perfused through the coronary vasculature significantly decreased infarct size and significantly enhanced post-ischemic myocardial function. In conclusion, the delivery of mitochondria through the coronary arteries resulted in their rapid

  15. A more consistent intraluminal rhesus monkey model of ischemic stroke

    PubMed Central

    Zhao, Bo; Shang, Guowei; Chen, Jian; Geng, Xiaokun; Ye, Xin; Xu, Guoxun; Wang, Ju; Zheng, Jiasheng; Li, Hongjun; Akbary, Fauzia; Li, Shengli; Lu, Jing; Ling, Feng; Ji, Xunming

    2014-01-01

    Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group: middle cerebral artery occlusion at origin segment (M1) and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique (1 mm × 10 cm) (undetachable), to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research. PMID:25657726

  16. Melatonin protects against ischemic heart failure in rats.

    PubMed

    Şehirli, Ahmet Özer; Koyun, Derya; Tetik, Şermin; Özsavcı, Derya; Yiğiner, Ömer; Çetinel, Şule; Tok, Olgu Enis; Kaya, Zehra; Akkiprik, Mustafa; Kılıç, Ertugrul; Şener, Göksel

    2013-09-01

    Ischemic injury, which occurs as a result of sympathetic hyperactivity, plays an important role in heart failure. Melatonin is thought to have antiatherogenic, antioxidant, and vasodilatory effects. In this study, we investigated whether melatonin protects against ischemic heart failure (HF). In Wistar albino rats, HF was induced by left anterior descending (LAD) coronary artery ligation and rats were treated with either vehicle or melatonin (10 mg/kg) for 4 weeks. At the end of this period, echocardiographic measurements were recorded and the rats were decapitated to obtain plasma and cardiac tissue samples. Lactate dehydrogenase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lysosomal enzymes (β-D-glucuronidase, β-galactosidase, β-D-N-acetyl-glucosaminidase, acid phosphatase, and cathepsin-D) were studied in plasma samples, while malondialdehyde and glutathione levels and Na+, K+-ATPase, caspase-3 and myeloperoxidase activities were determined in the cardiac samples. Sarco/endoplasmic reticulum calcium ATPase (SERCA) and caveolin-3 levels in cardiac tissues were evaluated using Western blot analyses. Furthermore, caveolin-3 levels were also determined by histological analyses. In the vehicle-treated HF group, cardiotoxicity resulted in decreased cardiac Na+, K+-ATPase and SERCA activities, GSH contents and caveolin-3 levels, while plasma LDH, CK, and lysosomal enzyme activities and cardiac MDA and Myeloperoxidase (MPO) activities were found to be increased. On the other hand, melatonin treatment reversed all the functional and biochemical changes. The present results demonstrate that Mel ameliorates ischemic heart failure in rats. These observations highlight that melatonin is a promising supplement for improving defense mechanisms in the heart against oxidative stress caused by heart failure.

  17. Intracranial versus extracranial artery dissection cases presenting with ischemic stroke.

    PubMed

    Chen, Hongbing; Hong, Hua; Xing, Shihui; Liu, Gang; Zhang, Aiwu; Tan, Shuangquan; Zhang, Jian; Zeng, Jinsheng

    2015-04-01

    To compare the clinical and radiologic characteristics, possible stroke mechanisms, and prognosis of intracranial artery dissections (IADs) with those of extracranial artery dissections (EADs) presenting with cerebral infarction. Among 3250 adult patients with acute ischemic stroke (cerebral infarction), we prospectively recruited and categorized patients with cerebral infarction secondary to spontaneous cerebral artery dissection into IAD or EAD groups. The clinical and radiologic characteristics, possible stroke mechanisms according to the distributions of the infarctions based on diffusion-weighted imaging, and prognosis were analyzed for both groups. There were 48 and 50 patients experiencing IAD and EAD, accounting for 1.5% and 1.5% of all ischemic stroke patients, respectively. Compression of the perforating artery was the most common possible stroke mechanism (33.3%) in IADs; thromboembolism was more common in EADs than that in IADs (36 of 50 versus 12 of 48; P < .001). Magnetic resonance imaging and angiography were used to investigate the arterial dissections in all IAD patients and 46 EAD patients. Based on magnetic resonance imaging and angiography, the IADs more frequently displayed dissecting aneurysm (6 of 48 versus 0 of 46; P = .027) and intimal flap or double lumen (21 of 48 versus 4 of 46; P < .001) than EADs. For the clinical characteristics and prognosis, there was no significant difference between the 2 groups. These results indicate that IAD is an important cause of ischemic stroke, and it displays unique radiologic characteristics and specific stroke mechanisms compared with EAD. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  18. [EEG and ischemic stroke in full-term newborns].

    PubMed

    Selton, D; André, M; Hascoët, J M

    2003-06-01

    The aims of this study were to describe EEG anomalies in unilateral neonatal ischemic stroke without hypoxic-ischemic encephalopathy, and to determine possible links between these abnormalities and long-term outcome. In 6 full-term newborns without severe fetal distress ischemic stroke was confirmed by computed tomography and/or magnetic resonance imaging. Twenty EEGs were recorded during the neonatal period, 5 in acute stage and 15 later. The duration of the follow-up ranged from 3 to 9 years. All newborns developed unilateral clonic seizures, right-sided (5 cases) or left-sided (1 case); seizures began between 14 and 48 h of life. At follow-up, 3 children were normal at 2 and 6 years of age, while the 3 others had sequelae: epilepsy at 9 years of age in one, and unilateral mild cerebral palsy in the 2 others (3 and 4 years of age), with behavioral problems in one of them. Critical EEG discharges, rhythmic sharp waves and/or slow waves were recorded on the injured side. Abnormalities of interictal activity were excess of alpha or theta rhythms, transitory EEG discontinuity or low voltage. The 2 children with cerebral palsy had numerous unilateral post-ictal positive rolandic slow sharp waves (PRSSWs), which were similar to the positive rolandic sharp waves of premature infants; the child with behavioral problems had numerous positive left-sided temporal fast sharp waves. PRSSWs could be associated with contralateral motor sequelae, while positive left temporal fast sharp waves were associated with long term behavioral problems. These findings may be used for future prospective studies aimed at specifying the relation between EEG abnormalities and long-term outcome.

  19. A more consistent intraluminal rhesus monkey model of ischemic stroke.

    PubMed

    Zhao, Bo; Shang, Guowei; Chen, Jian; Geng, Xiaokun; Ye, Xin; Xu, Guoxun; Wang, Ju; Zheng, Jiasheng; Li, Hongjun; Akbary, Fauzia; Li, Shengli; Lu, Jing; Ling, Feng; Ji, Xunming

    2014-12-01

    Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group: middle cerebral artery occlusion at origin segment (M1) and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique (1 mm × 10 cm) (undetachable), to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research.

  20. Hypoalgesic effect of caffeine in experimental ischemic muscle contraction pain.

    PubMed

    Myers, D E; Shaikh, Z; Zullo, T G

    1997-01-01

    It has been theorized that adenosine is a leading candidate for the metabolite responsible for ischemic muscle pain. The purpose of this study was to determine the effect of the non-selective adenosine receptor antagonist, caffeine, on ischemic skeletal muscle contraction pain. Seven healthy adult volunteers with no history of pain disorders, systemic disease, or habitual caffeine use, were chosen for the two-session, cross-over, double-blind study. Every subject received either 200 mg of caffeine (NoDoz, Bristol-Myers) or identical placebo 1 hour before each of the two trials. Ischemia of the forearm was achieved by inflation of a blood pressure cuff to 250 mm Hg. Forearm muscle activity was generated by performance of wrist curis using a 5-gram bar at a rate of 40 cycles per minute. Pain was rated at 15-second intervals for 1 minute using a visual analog scale (0 to 10) with verbal descriptors. Significance was determined by univariate and multivariate analyses of variance and covariance including repeated measures. Pain ratings at 15 seconds in the caffeine trial were significantly lower (P < 0.02) than those in the placebo trial. This effect continued at 30 seconds (P < 0.05). However, by 45 seconds, pain in the caffeine trial was not significantly lower (P = 0.4) than that in the placebo trial. These results show that high-dose caffeine exhibits considerable analgesic efficacy in experimental muscle pain, adding support for a role of adenosine in producing ischemic muscle contraction pain.

  1. Gene variants associated with ischemic stroke: the cardiovascular health study.

    PubMed

    Luke, May M; O'Meara, Ellen S; Rowland, Charles M; Shiffman, Dov; Bare, Lance A; Arellano, Andre R; Longstreth, W T; Lumley, Thomas; Rice, Kenneth; Tracy, Russell P; Devlin, James J; Psaty, Bruce M

    2009-02-01

    The purpose of this study was to determine whether 74 single nucleotide polymorphisms (SNPs), which had been associated with coronary heart disease, are associated with incident ischemic stroke. Based on antecedent studies of coronary heart disease, we prespecified the risk allele for each of the 74 SNPs. We used Cox proportional hazards models that adjusted for traditional risk factors to estimate the associations of these SNPs with incident ischemic stroke during 14 years of follow-up in a population-based study of older adults: the Cardiovascular Health Study (CHS). In white CHS participants, the prespecified risk alleles of 7 of the 74 SNPs (in HPS1, ITGAE, ABCG2, MYH15, FSTL4, CALM1, and BAT2) were nominally associated with increased risk of stroke (one-sided P<0.05, false discovery rate=0.42). In black participants, the prespecified risk alleles of 5 SNPs (in KRT4, LY6G5B, EDG1, DMXL2, and ABCG2) were nominally associated with stroke (one-sided P<0.05, false discovery rate=0.55). The Val12Met SNP in ABCG2 was associated with stroke in both white (hazard ratio, 1.46; 90% CI, 1.05 to 2.03) and black (hazard ratio, 3.59; 90% CI, 1.11 to 11.6) participants of CHS. Kaplan-Meier estimates of the 10-year cumulative incidence of stroke were greater among Val allele homozygotes than among Met allele carriers in both white (10% versus 6%) and black (12% versus 3%) participants of CHS. The Val12Met SNP in ABCG2 (encoding a transporter of sterols and xenobiotics) was associated with incident ischemic stroke in white and black participants of CHS.

  2. Stroke Code Improves Intravenous Thrombolysis Administration in Acute Ischemic Stroke

    PubMed Central

    Chen, Chih-Hao; Tang, Sung-Chun; Tsai, Li-Kai; Hsieh, Ming-Ju; Yeh, Shin-Joe; Huang, Kuang-Yu; Jeng, Jiann-Shing

    2014-01-01

    Background and Purpose Timely intravenous (IV) thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with “Stroke Code” (SC) may increase IV tissue plasminogen activator (tPA) administration. The present study aimed to investigate the impact of SC on thrombolysis. Methods The study period was divided into the “pre-SC era” (January 2006 to July 2010) and “SC era” (August 2010 to July 2013). Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis), stroke severity, and clinical outcomes were recorded and compared between the two eras. Results During the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8%) arrived at the emergency department within 3 h of stroke onset and 307 (5.2%) received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of <3 h increased from the pre-SC era (n = 91, 13.9%) to the SC era (n = 216, 33.3%) (P<0.001). SC also improved the efficiency of IV-tPA administration; the median door-to-needle time decreased (88 to 51 min, P<0.001) and the percentage of door-to-needle times ≤60 min increased (14.3% to 71.3%, P<0.001). The SC era group tended to have more patients with good outcome (modified Rankin Scale ≤2) at discharge (49.5 vs. 39.6%, P = 0.11), with no difference in symptomatic hemorrhage events or in-hospital mortality. Conclusion The SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time. PMID:25111200

  3. Thyroid hormones and functional outcomes after ischemic stroke.

    PubMed

    O'Keefe, Lena M; Conway, Sarah E; Czap, Alexandra; Malchoff, Carl D; Benashski, Sharon; Fortunato, Gilbert; Staff, Ilene; McCullough, Louise D

    2015-01-01

    Stroke is the fifth leading cause of death and the primary cause of long-term adult disability in the United States. Increasing evidence suggests that low T3 levels immediately following acute ischemic stroke are associated with greater stroke severity, higher mortality rates, and poorer functional outcomes. Prognosis is also poor in critically ill hospitalized patients who have non-thyroidal illness syndrome (NTIS), where T3 levels are low, but TSH is normal. However, data regarding the association between TSH levels and functional outcomes are contradictory. Thus, this study investigated the role of TSH on stroke outcomes, concomitantly with T3 and T4. In this work, blood was collected from patients with radiologically confirmed acute ischemic stroke at 24±6 hours post-symptom onset and serum levels of TSH, free T3, and free T4 were measured. Stroke outcomes were measured at discharge, 3 and 12 months using the modified Rankin scale and modified Barthel Index as markers of disability. Though we found that lower levels of free T3 were associated with worse prognosis at hospital discharge, and at 3 and 12 months post-stroke, none of these outcomes held after multivariate analysis. Thus, it is likely that thyroid hormones are associated with other factors that impact stroke outcomes, such as sex, age and stroke etiology. This study found that lower levels of free T3 were associated with poorer outcomes at hospital discharge, and at 3 and 12 months post stroke, however, these associations diminished after correction for other known predictors of stroke outcome. Thyroid hormones have a complex relationship with ischemic stroke and stroke recovery, which merits further larger investigations.

  4. Tracheostomy following severe ischemic stroke: a population based study

    PubMed Central

    Walcott, Brian P.; Kamel, Hooman; Castro, Brandyn; Kimberly, W. Taylor; Sheth, Kevin N.

    2013-01-01

    Goal Stroke can result in varying degrees of respiratory failure. Some patients require tracheostomy in order to facilitate weaning from mechanical ventilation, long-term airway protection, or a combination of the two. Little is known about the rate and predictors of this outcome in patients with severe stroke. We aim to determine the rate of tracheostomy after severe ischemic stroke. Materials & Methods Using the Nationwide Inpatient Sample database from 2007–2009, patients hospitalized with ischemic stroke were identified based on validated International Classification of Diseases, 9th Revision, Clinical Modification codes. Next, patients with stroke were stratified based on whether they were treated with or without decompressive craniectomy, and the rate of tracheostomy for each group was determined. A logistic regression analysis was used to identify predictors of tracheostomy after decompressive craniectomy. Survey weights were used to obtain nationally representative estimates. Findings In 1,550,000 patients discharged with ischemic stroke nationwide, the rate of tracheostomy was 1.3% (95% CI, 1.2–1.4%), with a 1.3% (95% CI, 1.1–1.4%) rate in patients without decompressive craniectomy and a 33% (95% CI, 26–39%) rate in the surgical-treatment group. Logistic regression analysis identified pneumonia as being significantly associated with tracheostomy after decompressive craniectomy (OR 3.95; 95% CI 1.95–6.91). Conclusion Tracheostomy is common following decompressive craniectomy and is strongly associated with the development of pneumonia. Given its impact on patient function and potentially modifiable associated factors, tracheostomy may warrant further study as an important patient-centered outcome among patients with stroke. PMID:24103666

  5. Tracheostomy after severe ischemic stroke: a population-based study.

    PubMed

    Walcott, Brian P; Kamel, Hooman; Castro, Brandyn; Kimberly, W Taylor; Sheth, Kevin N

    2014-01-01

    Stroke can result in varying degrees of respiratory failure. Some patients require tracheostomy in order to facilitate weaning from mechanical ventilation, long-term airway protection, or a combination of the two. Little is known about the rate and predictors of this outcome in patients with severe stroke. We aim to determine the rate of tracheostomy after severe ischemic stroke. Using the Nationwide Inpatient Sample database from 2007 to 2009, patients hospitalized with ischemic stroke were identified based on validated International Classification of Diseases, 9th revision, Clinical Modification codes. Next, patients with stroke were stratified based on whether they were treated with or without decompressive craniectomy, and the rate of tracheostomy for each group was determined. A logistic regression analysis was used to identify predictors of tracheostomy after decompressive craniectomy. Survey weights were used to obtain nationally representative estimates. In 1,550,000 patients discharged with ischemic stroke nationwide, the rate of tracheostomy was 1.3% (95% confidence interval [CI], 1.2-1.4%), with a 1.3% (95% CI, 1.1-1.4%) rate in patients without decompressive craniectomy and a 33% (95% CI, 26-39%) rate in the surgical treatment group. Logistic regression analysis identified pneumonia as being significantly associated with tracheostomy after decompressive craniectomy (odds ratio, 3.95; 95% CI, 1.95-6.91). Tracheostomy is common after decompressive craniectomy and is strongly associated with the development of pneumonia. Given its impact on patient function and potentially modifiable associated factors, tracheostomy may warrant further study as an important patient-centered outcome among patients with stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  6. Dynamic thiol-disulfide homeostasis in acute ischemic stroke patients.

    PubMed

    Bektas, Hesna; Vural, Gonul; Gumusyayla, Sadiye; Deniz, Orhan; Alisik, Murat; Erel, Ozcan

    2016-12-01

    Dynamic thiol-disulfide homeostasis plays a critical role in the cellular protection provided by antioxidation. The aim of this study was to investigate whether there is a change in thiol-disulfide homeostasis in acute ischemic stroke patients. Patients diagnosed with acute ischemic stroke that had undergone magnetic resonance diffusion-weighted imaging within the first 24 h were prospectively included in this study. The thiol, disulfide, and total thiol levels were measured during the first 24 and 72 h, and the National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) of the patients were recorded. Overall, the relationships between the thiol-disulfide levels of the patients and the infarct volumes, NIHSS, mRS, and BI scores were investigated. In this study, 54 patients and 53 healthy controls were included. The mean of the native thiol levels in the stroke group was 356.572 ± 61.659 μmol/L (min/max 228.00/546.40), while it was 415.453 ± 39.436 μmol/L (min/max 323.50/488.70) in the control group (p < 0.001). A negative, significant correlation was observed between the infarct volumes and native thiol levels (ρ = -0.378; p = 0.005), and the disulfide levels were similar between the groups (Z = 0.774; p = 0.439). Significant difference was found between the thiol levels of the mild and moderate-severe NIHSS groups (p = 0.026). The changes in the thiol levels under oxidative stress may be associated with the severity of the stroke. Substitution of thiol deficiency and correction of thiol-disulfide imbalance may be beneficial in ischemic stroke.

  7. Magnetic Resonance Imaging in Acute Ischemic Stroke Treatment

    PubMed Central

    Kim, Bum Joon; Kang, Hyun Goo; Kim, Hye-Jin; Ahn, Sung-Ho; Kim, Na Young; Warach, Steven

    2014-01-01

    Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis. PMID:25328872

  8. Stroke code improves intravenous thrombolysis administration in acute ischemic stroke.

    PubMed

    Chen, Chih-Hao; Tang, Sung-Chun; Tsai, Li-Kai; Hsieh, Ming-Ju; Yeh, Shin-Joe; Huang, Kuang-Yu; Jeng, Jiann-Shing

    2014-01-01

    Timely intravenous (IV) thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with "Stroke Code" (SC) may increase IV tissue plasminogen activator (tPA) administration. The present study aimed to investigate the impact of SC on thrombolysis. The study period was divided into the "pre-SC era" (January 2006 to July 2010) and "SC era" (August 2010 to July 2013). Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis), stroke severity, and clinical outcomes were recorded and compared between the two eras. During the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8%) arrived at the emergency department within 3 h of stroke onset and 307 (5.2%) received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of <3 h increased from the pre-SC era (n = 91, 13.9%) to the SC era (n = 216, 33.3%) (P<0.001). SC also improved the efficiency of IV-tPA administration; the median door-to-needle time decreased (88 to 51 min, P<0.001) and the percentage of door-to-needle times ≤60 min increased (14.3% to 71.3%, P<0.001). The SC era group tended to have more patients with good outcome (modified Rankin Scale ≤2) at discharge (49.5 vs. 39.6%, P = 0.11), with no difference in symptomatic hemorrhage events or in-hospital mortality. The SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time.

  9. Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection.

    PubMed

    Cowan, Douglas B; Yao, Rouan; Akurathi, Vamsidhar; Snay, Erin R; Thedsanamoorthy, Jerusha K; Zurakowski, David; Ericsson, Maria; Friehs, Ingeborg; Wu, Yaotang; Levitsky, Sidney; Del Nido, Pedro J; Packard, Alan B; McCully, James D

    2016-01-01

    We have previously shown that transplantation of autologously derived, respiration-competent mitochondria by direct injection into the heart following transient ischemia and reperfusion enhances cell viability and contractile function. To increase the therapeutic potential of this approach, we investigated whether exogenous mitochondria can be effectively delivered through the coronary vasculature to protect the ischemic myocardium and studied the fate of these transplanted organelles in the heart. Langendorff-perfused rabbit hearts were subjected to 30 minutes of ischemia and then reperfused for 10 minutes. Mitochondria were labeled with 18F-rhodamine 6G and iron oxide nanoparticles. The labeled mitochondria were either directly injected into the ischemic region or delivered by vascular perfusion through the coronary arteries at the onset of reperfusion. These hearts were used for positron emission tomography, microcomputed tomography, and magnetic resonance imaging with subsequent microscopic analyses of tissue sections to confirm the uptake and distribution of exogenous mitochondria. Injected mitochondria were localized near the site of delivery; while, vascular perfusion of mitochondria resulted in rapid and extensive dispersal throughout the heart. Both injected and perfused mitochondria were observed in interstitial spaces and were associated with blood vessels and cardiomyocytes. To determine the efficacy of vascular perfusion of mitochondria, an additional group of rabbit hearts were subjected to 30 minutes of regional ischemia and reperfused for 120 minutes. Immediately following regional ischemia, the hearts received unlabeled, autologous mitochondria delivered through the coronary arteries. Autologous mitochondria perfused through the coronary vasculature significantly decreased infarct size and significantly enhanced post-ischemic myocardial function. In conclusion, the delivery of mitochondria through the coronary arteries resulted in their rapid

  10. Transient Global Amnesia and the Risk of Ischemic Stroke

    PubMed Central

    Mangla, Atul; Navi, Babak B.; Layton, Kelly; Kamel, Hooman

    2013-01-01

    Background and Purpose It remains unclear whether transient global amnesia (TGA) represents an arterial insult that heralds ischemic stroke. We therefore examined stroke risk after TGA in a population-based cohort. Methods After performing chart review at our institution to validate the ICD-9-CM diagnosis code for TGA, we used administrative claims data to identify all patients discharged from nonfederal California emergency departments or acute care hospitals between 2005 through 2010 with a primary discharge diagnosis of TGA. Patients with a primary discharge diagnosis of migraine, seizure, or transient ischemic attack (TIA) were included as controls. Kaplan-Meier statistics were used to calculate rates of ischemic stroke, and Cox proportional hazards analyses were used to compare stroke risk among the four exposure groups while controlling for traditional stroke risk factors. Results ICD-9-CM code 437.7 had a sensitivity of 86% and a specificity of 95% for TGA. The cumulative 1-year rate of stroke was 0.54% (95% confidence interval [CI], 0.36–0.81%) after TGA, 0.22% (95% CI, 0.20–0.25%) after migraine, 0.90% (95% CI, 0.83–0.97%) after seizure, and 4.72% (95% CI, 4.60–4.85%) after TIA. After adjustment for demographic characteristics and stroke risk factors, TGA was not associated with stroke risk when compared to migraine (hazard ratio [HR], 0.82; 95% CI, 0.61–1.10). The likelihood of stroke after TGA was lower than after seizure (HR, 0.57; 95% CI, 0.44–0.76) or TIA (HR, 0.27; 95% CI, 0.20–0.35). Conclusions Compared to patients diagnosed with migraine or seizure, patients diagnosed with TGA do not appear to face a heightened risk of stroke. PMID:24309586

  11. Flow cytometric analysis of inflammatory cells in ischemic rat brain.

    PubMed

    Campanella, Marilena; Sciorati, Clara; Tarozzo, Glauco; Beltramo, Massimiliano

    2002-02-01

    Inflammation plays a key role in cerebral ischemia through activation of microglia and infiltration by leukocytes. Flow cytometry is a well-established method for quantitative and qualitative analysis of inflammatory cells. However, this technique has not been applied to the study of cerebral ischemia inflammation. The aim of this study was to establish a flow cytometric method to measure inflammatory cells in ischemic brain. To perform flow cytometry on brain tissue, we developed 2 cell-isolation methods based on different mechanical dissociation and Percoll gradient separation techniques. The methods were tested on a rat model of permanent middle cerebral artery occlusion. Morphological and immunophenotypic analyses, with the use of anti-CD11b, anti-CD45, and alphabeta T-cell receptor antibodies, were employed to identify and quantify inflammatory cells. Both methods gave consistent results in terms of yield and reproducibility. The cell suspension contained granulocytes, macrophages, lymphocytes, and neural cells. Morphological and immunophenotypic analyses enabled the identification of a cell-scatter gate (R1a) enriched in inflammatory cells. With both methods, a higher number of events in R1a were recorded in the ischemic hemisphere than in the nonischemic hemisphere (P< or =0.001). CD11b, CD45, and alphabeta T-cell receptor staining confirmed that this augmentation was a reflection of the increase in the number of granulocytes, cells of the monocytic lineage, and lymphocytes. Quantitative flow cytometric analysis of ischemic rat brain is feasible and provides a reliable and rapid assay to assess neuroinflammation in experimental models of brain ischemia.

  12. Rosiglitazone, myocardial ischemic risk, and recent regulatory actions.

    PubMed

    Bourg, Catherine A; Phillips, Beth Bryles

    2012-02-01

    To review the evidence surrounding rosiglitazone and ischemic cardiovascular risk and discuss the Food and Drug Administration (FDA) decision to revise safety information and restrict access to the drug. A literature search was conducted through MEDLINE (1950-January 2012), PubMed (1966-January 2012), and International Pharmaceutical Abstracts (1970-December 2011) using the search terms rosiglitazone and cardiovascular risk. Regulatory documents from the FDA and the Center for Drug Evaluation and Research, as well as reference citations from publications identified, were reviewed. All articles in English identified from the data sources were evaluated for inclusion. Literature regarding rosiglitazone and ischemic cardiovascular risk has shown inconsistent results. Meta-analyses by the FDA, GlaxoSmithKline, and several independent research groups suggest an increased risk for myocardial infarction (MI), while others have not. Long-term, controlled trials not designed to evaluate cardiovascular outcomes did not find a significant increase in cardiovascular events and had low event rates overall. The RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes in Oral Agent Combination Therapy for Type 2 Diabetes) trial is the only prospective randomized trial to date designed to evaluate cardiovascular outcomes of rosiglitazone; the results were limited because of issues with study design and event adjudication. The only direct comparisons between rosiglitazone and pioglitazone are observational studies in which pioglitazone had a more favorable MI risk profile. Data involving rosiglitazone and an association with ischemic cardiovascular risk have yielded variable results. The FDA made the decision to restrict access to rosiglitazone in September 2010 by requiring GlaxoSmithKline to submit a risk evaluation and mitigation strategy (REMS). Drug labeling was revised in February 2011, and the rosiglitazone REMS program took full effect in November 2011.

  13. Peripheral pulse measurement after ischemic stroke: A feasibility study.

    PubMed

    Kallmünzer, Bernd; Bobinger, Tobias; Kahl, Nicolas; Kopp, Markus; Kurka, Natalia; Hilz, Max-Josef; Marquardt, Lars; Schwab, Stefan; Köhrmann, Martin

    2014-08-12

    To investigate feasibility and diagnostic accuracy of measurement of the peripheral pulse (MPP) at the radial artery as a simple, noninvasive screening tool for paroxysmal atrial fibrillation (pAF) in patients after acute ischemic stroke. Two hundred fifty-six patients with acute ischemic stroke and the patients' relatives at a tertiary stroke center were prospectively included. Participants were instructed for characteristics of atrial fibrillation (AF) in MPP using standardized educational material. Measurements of participants as well as a health care professional were then compared with simultaneous blinded ECG to evaluate diagnostic accuracy parameters. MPP by the health care professional or patients' relatives had a diagnostic sensitivity of 96.5% and 76.5%, respectively, with 94.0% and 92.9% specificity for the detection of AF. Self-measurements were reliably performed by 89.1% of competent patients with a diagnostic sensitivity of 54.1% and 96.2% specificity. False-positive results were limited to 6 cases (2.7%) with a positive predictive value of 76.9% and a negative predictive value of 90.0%. With a low rate of false-positive results, MPP offers an easy, ubiquitously available, noninvasive, first-step screening tool to guide ECG diagnostics for pAF after ischemic stroke. The data warrant a prospective trial evaluating the efficacy of MPP-guided ECG diagnostics in secondary prevention after stroke, which is now underway. This study provides Class I evidence that MPP by patients or relatives accurately distinguishes AF from normal heart rhythm as compared with continuous ECG. © 2014 American Academy of Neurology.

  14. Chronic nicotine exposure exacerbates acute renal ischemic injury.

    PubMed

    Arany, Istvan; Grifoni, Samira; Clark, Jeb S; Csongradi, Eva; Maric, Christine; Juncos, Luis A

    2011-07-01

    Recent epidemiological reports showed that smoking has a negative impact on renal function and elevates the renal risk not only in the renal patient but perhaps also in the healthy population. Studies suggested that nicotine, a major tobacco alkaloid, links smoking to renal dysfunction. While several studies showed that smoking/chronic nicotine exposure exacerbates the progression of chronic renal diseases, its impact on acute kidney injury is virtually unknown. Here, we studied the effects of chronic nicotine exposure on acute renal ischemic injury. We found that chronic nicotine exposure increased the extent of renal injury induced by warm ischemia-reperfusion as evidenced by morphological changes, increase in plasma creatinine level, and kidney injury molecule-1 expression. We also found that chronic nicotine exposure elevated markers of oxidative stress such as nitrotyrosine as well as malondialdehyde. Interestingly, chronic nicotine exposure alone increased oxidative stress and injury in the kidney without morphological alterations. Chronic nicotine treatment not only increased reactive oxygen species (ROS) production and injury but also exacerbated oxidative stress-induced ROS generation through NADPH oxidase and mitochondria in cultured renal proximal tubule cells. The resultant oxidative stress provoked injury through JNK-mediated activation of the activator protein (AP)-1 transcription factor in vitro. This mechanism might exist in vivo as phosphorylation of JNK and its downstream target c-jun, a component of the AP-1 transcription factor, is elevated in the ischemic kidneys exposed to chronic nicotine. Our results imply that smoking may sensitize the kidney to ischemic insults and perhaps facilitates progression of acute kidney injury to chronic kidney injury.

  15. Glycosylated Hemoglobin and Functional Outcome after Acute Ischemic Stroke.

    PubMed

    Lattanzi, Simona; Bartolini, Marco; Provinciali, Leandro; Silvestrini, Mauro

    2016-07-01

    Diabetes mellitus (DM) is associated to an increased incidence of cerebral and myocardial infarction which could be reduced by long-term maintenance of optimal glycemic values. The aim of the study was to evaluate in diabetic patients with ischemic stroke the chronic glycemic status and its relationship with functional outcome. We retrospectively identified consecutive diabetic patients hospitalized for acute ischemic stroke. Clinical and biochemical characteristics at admission were assessed. The outcome measures were the attainment of the recommended glycosylated hemoglobin A1 (HbA1c) level and the 3-month functional status according to the modified Rankin Scale score. Among the 112 enrolled patients, 39 (34.8%) met the recommended goal of HbA1c less than 7%. Higher education level was predictive of good prestroke glycemic control (adjusted OR 1.32 per year [95% CI 1.15-1.51], P < .001). At the 3-month evaluation, 44 (39.3%) patients were classified as having a poor outcome. After categorization of HbA1c values into tertiles, a dose-response relationship with poor functional recovery was found (P = .001). The suboptimal prestroke glycemic status was an independent predictor of unfavorable outcome (adjusted OR 6.22 [95% CI 1.94-19.98] for HbA1c ≥7%, P = .002). The management of DM was suboptimal in nearly two thirds of diabetic subjects presenting with acute ischemic stroke. The glycemic control before stroke occurrence was an independent prognostic factor and HbA1c values above the recommended goals increased the risk of unfavorable 3-month outcome. The improvement of DM management may be an effective strategy to either decrease the burden of cerebrovascular disease or influence its clinical course. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Implication of left ventricular diastolic dysfunction in cryptogenic ischemic stroke.

    PubMed

    Seo, Jae-Young; Lee, Kyung Bok; Lee, Jung-Gon; Kim, Ji-Sun; Roh, Hakjae; Ahn, Moo-Young; Park, Byoung Won; Hyon, Min Su

    2014-09-01

    Left ventricular diastolic dysfunction (LVDD) is a predictor for atrial fibrillation (AF). This study was aimed to investigate whether LVDD in cryptogenic ischemic stroke (CS) could be a clue to stroke mechanism. The clinical and echocardiographic findings of 1589 consecutive patients with acute ischemic stroke or transient ischemic attack between 2004 and 2013 were reviewed. LVDDs among stroke subtypes were graded by transthoracic echocardiography into 4 groups by severity: normal, abnormal relaxation (grade I), pseudonormal (grade II), and restrictive diastolic filling (grade III), whereas severe LVDD was defined as grade III. We classified the lesion pattern of CS into cardioembolism-mimic or non-cardioembolism-mimic and determined whether cardioembolism-mimic lesions were associated with severe LVDD. The fraction of severe LVDD in CS was not different from that of stroke with AF (27.3% versus 37.1%; P=0.173) but was significantly higher than that of stroke without AF (27.3% versus 13.4%; P=0.008). Cardioembolism-mimic CS had more severe LVDD than non-cardioembolism-mimic CS (41.4% versus 11.5%; P=0.013). LVDD of grade II (odds ratio, 4.37; 95% confidence interval, 2.99-6.41) and grade III (odds ratio, 5.60; 95% confidence interval, 3.42-9.17) were independently related to stroke with AF after adjusting covariates. The severe LVDD could be a predictor of stroke with AF, and its frequency was similar between CS and stroke with AF. Cardioembolism-mimic CS had significantly more severe LVDD than non-cardioembolism-mimic CS. LVDD could be helpful to discriminate the stroke mechanism in the patients with acute CS. © 2014 American Heart Association, Inc.

  17. Stem Cells for Ischemic Brain Injury: A Critical Review

    PubMed Central

    Burns, Terry C.; Verfaillie, Catherine M.; Low, Walter C.

    2014-01-01

    No effective therapy is currently available to promote recovery following ischemic stroke. Stem cells have been proposed as a potential source of new cells to replace those lost due to central nervous system injury, as well as a source of trophic molecules to minimize damage and promote recovery. We undertook a detailed review of data from recent basic science and preclinical studies to investigate the potential application of endogenous and exogenous stem cell therapies for treatment of cerebral ischemia. To date, spontaneous endogenous neurogenesis has been observed in response to ischemic injury, and can be enhanced via infusion of appropriate cytokines. Exogenous stem cells from multiple sources can generate neural cells that survive and form synaptic connections after transplantation in the stroke-injured brain. Stem cells from multiple sources cells also exhibit neuroprotective properties that may ameliorate stroke deficits. In many cases, functional benefits observed are likely independent of neural differentiation, though exact mechanisms remain poorly understood. Future studies of neuroregeneration will require the demonstration of function in endogenously born neurons following focal ischemia. Further, methods are currently lacking to definitively demonstrate the therapeutic effect of newly introduced neural cells. Increased plasticity following stroke may facilitate the functional integration of new neurons, but the loss of appropriate guidance cues and supporting architecture in the infarct cavity will likely impede the restoration of lost circuitry. As such careful investigation of the mechanisms underlying trophic benefits will be essential. Evidence to date suggest that continued development of stem cell therapies may ultimately lead to viable treatment options for ischemic brain injury. PMID:19399885

  18. Magnetic resonance imaging in acute ischemic stroke treatment.

    PubMed

    Kim, Bum Joon; Kang, Hyun Goo; Kim, Hye-Jin; Ahn, Sung-Ho; Kim, Na Young; Warach, Steven; Kang, Dong-Wha

    2014-09-01

    Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Theref