Cerebral Ischemic Attacks Research Articles

Recurrent Stroke and Bleeding Events after Acute Cardioembolic Stroke—Analysis Using Japanese Healthcare Database from Acute-Care Institutions

To understand the reality of patients who experienced a cardioembolic stroke (CES) is important because of the high incidence of recurrent stroke and the need to account for bleeding risk in relation to the need for anticoagulation treatment. We elucidated the current real-world medical care in patients who had a CES and identified the risk factors for recurrent stroke. The study comprised 9804 patients who were diagnosed with CES between April 2008 and September 2013 as identified in a healthcare database used by acute-care institutions in Japan. We analyzed the incidence and risk factors of stroke and bleeding events in CES patients. The incidence of stroke was 10.3% during the median observation period of 68 days, mainly consisting of recurrent CES (8.5%). The incidence of bleeding events and intracranial bleeding was 10.3% and 7.0%, respectively. The recurrence of ischemic stroke was significantly lower, and brain hemorrhage was significantly higher in the anticoagulation treatment group. The factors related to an increased risk of stroke were a history of cerebral infarction or transient ischemic attack, diabetes, and increase of CHA2DS2-VASc and CHADS2 scores. The risk factors for bleeding events were hypertension, renal dysfunction, and use of proton pump inhibitors (PPIs). The patients who experienced CES had a high rate of recurrent stroke or CES, mainly consisting of recurrent CES. Although anticoagulation may be beneficial for reducing recurrence of ischemic stroke, careful management is required given consideration of increased risk of brain hemorrhage during anticoagulation treatment, especially for patients with hypertension, renal dysfunction, and use of PPIs.

Validation of an algorithm that determines stroke diagnostic code accuracy in a Japanese hospital-based cancer registry using electronic medical records

BackgroundThis study aimed to validate an algorithm that determines stroke diagnostic code accuracy, in a hospital-based cancer registry, using electronic medical records (EMRs) in Japan.MethodsThe subjects were 27,932 patients enrolled in the hospital-based cancer registry of Osaka University Hospital, between January 1, 2007 and December 31, 2015. The ICD-10 (international classification of diseases, 10th revision) diagnostic codes for stroke were extracted from the EMR database. Specifically, subarachnoid hemorrhage (I60); intracerebral hemorrhage (I61); cerebral infarction (I63); and other transient cerebral ischemic attacks and related syndromes and transient cerebral ischemic attack (unspecified) (G458 and G459), respectively. Diagnostic codes, both “definite” and “suspected,” and brain imaging information were extracted from the database. We set the algorithm with the combination of the diagnostic code and/or the brain imaging information, and manually reviewed the presence or absence of the acute cerebrovascular disease with medical charts.ResultsA total of 2654 diagnostic codes, 1991 “definite” and 663 “suspected,” were identified. After excluding duplicates, the numbers of “definite” and “suspected” diagnostic codes were 912 and 228, respectively. The proportion of the presence of the disease in the “definite” diagnostic code was 22%; this raised 51% with the combination of the diagnostic code and the use of brain imaging information. When adding the interval of when brain imaging was performed (within 30 days and within 1 day) to the diagnostic code, the proportion increased to 84% and 90%, respectively. In the algorithm of “definite” diagnostic code, history of stroke was the most common in the diagnostic code, but in the algorithm of “definite” diagnostic code and the use of brain imaging within 1 day, stroke mimics was the most frequent.ConclusionsCombining the diagnostic code and clinical examination improved the proportion of the presence of disease in the diagnostic code and achieved appropriate accuracy for research. Clinical research using EMRs require outcome validation prior to conducting a study.

Gene polymorphisms of fibronectin rs2289202 and fibrillin 2 rs331069 associate with vascular disease, the TAMRISK study.

Cell surface heparan sulfate (HS) proteoglycans interact with other extracellular matrix (ECM) components, and HS-binding regions are present in ECM proteins such as fibronectin and fibrillin. Because of their previously established role in susceptibility to intracranial aneurysms, the authors sought to determine whether polymorphisms of fibronectin (FN1, rs2289202) and fibrillin 2 (FBN2, rs331069) associate with selected cardiovascular risk factors and events in the TAMRISK study. A 50-year-old Finnish cohort of 810 subjects of whom 340 had diagnosed hypertension was analyzed. Samples were genotyped for FN1 rs2289202 and FBN2 rs331069 polymorphisms. Incidence of myocardial infarction (I21-I22), transient cerebral ischemic attacks (TIA, G45) and cerebrovascular diseases (I60-I69) were followed up until the subjects were on the average 60 years old. Subjects with FN1 rs2289202 (G>A) minor genotype AA had significantly more cerebrovascular disease than those with the G allele [P<0.001, odds ratio (OR), 8.73; confidence index (CI), 2.79-27.31], although those with the A allele had lower body mass index (P=0.008). Subjects with fibrillin rs331069 (T>C) minor genotype CC had more atherothrombotic disease (P=0.012, OR, 3.16; CI, 1.29-7.71), as measured by combined myocardial infarction and TIA, than those with the T allele. The gene polymorphisms for fibronectin and fibrillin 2 appear to associate with vascular disease.

Influence of cerebrovascular reactivity on outcome of the patients with ≥50% symptomatic unilateral middle cerebral artery stenosis

ABSTRACTPurpose/aim of the study: Cerebrovascular reactivity (CVR) reflects the vasodilatory reserve of cerebral resistance vessels, which is an important marker for assessing cerebrovascular disease. The present study is to investigate whether CVR impairment increases adverse long-term outcome risk of patients with ≥ 50% symptomatic unilateral middle cerebral artery (MCA) stenosis (ischemic stroke (IS) or transient ischemic attack (TIA)).Material and methods: Digital subtraction angiography (DSA) was used to assess the degree of stenosis, and perfusion CT and 5% CO2 inhalation were adopted to evaluate CVR. Patients with ≥ 50% symptomatic unilateral MCA stenosis were assigned to non-CVR impairment group and CVR impairment group according to CVR status. The long-term follow-up endpoint was composite of any IS ( in the territory of the studied MCA) or death within 12 months.Results: Seventy-three patients with ≥ 50% symptomatic unilateral MCA stenosis, involving 31 non-CVR impairment cases and 42 CVR impairment cases, were included in the present study. Finally, IS occurred in six CVR impairment patients, and no endpoint happened in the non-CVR impairment group. Therefore, the annual rate of IS was 14.29% in the CVR impairment group and 0% in the non-CVR impairment group (P = 0.035). Besides, further Kaplan-Meier analysis found CVR impairment was closely associated with the IS risk (Kaplan-Meier Log-rank 4.719, P = 0.030).Conclusions: Our results showed that for patients with ≥ 50% symptomatic unilateral MCA stenosis, there was significant difference between non-CVR impairment cases and CVR impairment cases in the annual rate of IS. It suggests that CVR impairment increases the risk of adverse long-term outcomes.

A case of Moyamoya disease with cerebral ischemic attack induced by standing position verified by the alteration of regional saturation of oxygen measured by near-infrared spectroscopy

A case of Moyamoya disease with cerebral ischemic attack induced by standing position verified by the alteration of regional saturation of oxygen measured by near-infrared spectroscopy

Cryptogenic ischemic stroke and prevalence of asymptomatic atrial fibrillation: a prospective study.

Atrial fibrillation is responsible for up to one-third of ischemic strokes, and is also associated with silent cerebral infarctions and transient ischemic attacks (TIAs). The self-terminating and often asymptomatic nature of paroxysmal atrial fibrillation (PAF) may lead to its underdiagnosis. A continuous and long-term heart rhythm monitoring can be useful in unmasking PAF episodes. Prevalence of asymptomatic PAF in patients suffering a cryptogenic stroke, at risk for atrial fibrillation but without any history of arrhythmia or palpitations, using a continuous electrocardiographic monitoring. One hundred and forty-two consecutive patients were admitted to the Stroke Unit of 'Città della Salute e della Scienza' Hospital of Turin between June 2010 and March 2013 and discharged with the diagnosis of ischemic cryptogenic stroke. Sixty fulfilled predefined inclusion criteria. Follow-up was carried on and completed for the 54 patients who consented to implantable loop recorder (ILR) implantation. After ILR implantation, trans-telephonic data were collected monthly. Atrial fibrillation episodes lasting more than 5 min were recorded in 25 patients (46%), median detection time was 5.4 months (range 1-18) and median duration of atrial fibrillation episodes was 20 h (range 7 min-8 days) with 19 patients (76%) remaining asymptomatic and the others experiencing weakness and dyspnoea but not palpitations. Long-term heart rhythm monitoring is successful in unmasking silent atrial fibrillation in 46% of patients suffering a cryptogenic stroke with concomitant atrial fibrillation risk factors, but without history of arrhythmia or palpitations.

Relation of serum homocysteine levels to cerebral artery calcification and atherosclerosis

Background and aimsElevated serum homocysteine level is known to be associated with increased risk of vascular event due to endothelial senescence. We investigated the association between serum homocysteine level and cerebral arteriosclerosis status including intracranial vascular calcification and atherosclerosis burden. MethodsWe identified 1193 consecutive patients (mean age = 68.6 ± 12.7, 537 female patients) who were admitted with acute cerebral infarction or transient ischemic attack from a single university medical center. The patients were categorized into three groups according to their serum homocysteine level. Cerebral artery calcification was assessed from the cavernous portion of both internal carotid arteries, and cerebral atherosclerosis burden was derived as the sum of stenosis degree of major intracranial arteries from brain computed tomography angiography. ResultsThe mean homocysteine level was 14.1 ± 6.2 μmol/L, and intracranial cerebral artery calcification was present in 974 patients (81.6%), with 339 cases of advanced calcification (28.4%). The prevalence of cerebral artery calcification, advanced cerebral artery calcification and cerebral atherosclerosis burden showed increasing tendency throughout the homocysteine tertiles. Multivariable logistic regression analysis including age, sex, vascular risk factors, serum C-reactive protein, estimated glomerular filtration rate and homocysteine tertile disclosed that the highest serum homocysteine tertile was an independent predictor of advanced cerebral artery calcification (odds ratio = 1.45, confidence interval = 1.02–2.05) and advanced cerebral atherosclerosis (odds ratio = 1.42, confidence interval = 1.01–1.99) compared to the lowest group. ConclusionsAn elevated serum homocysteine level was independently associated with intracranial arterial calcification and atherosclerosis burden. Future studies are warranted to test whether lowering serum homocysteine can delay cerebral arteriosclerotic changes.

Glucuronic Acid Epimerase (GLCE) Variant rs3865014 (A>G) Is Associated with BMI, Blood Hemoglobin, Hypertension, and Cerebrovascular Events, the TAMRISK Study.

Heparan sulfate proteoglycans modulate many physiological systems, and genes responsible for proteoglycan assembly and disassembly may affect their interaction. We sought to determine whether polymorphisms of the glucuronic acid epimerase (GLCE) rs3865014 and sulfatase-2 (SULF2) rs2281279, genes coding for enzymes participating in heparan sulfate side chain activity, associate with hypertension, selected cardiometabolic risk factors and cardiovascular events in the Tampere adult population cardiovascular risk study. A Finnish cohort of 339 subjects with diagnosed hypertension and 441 controls was analyzed. Samples were genotyped for GLCE rs3865014 (A>G) and SULF2 rs2281279 (T>C) polymorphisms using competitive allele-specific PCR (KASP) technique. Prevalence of ischemic heart diseases (I20-I25) and incidence of cerebrovascular diseases (I60-I69) and transient cerebral ischemic attacks (TIA) (G45) were followed up until the subjects were on the average 60 years old. GLCE rs3865014 G allele showed negative association with hypertension (p = 0.022), waist circumference (p = 0.032), BMI (p = 0.048), and positive association with hemoglobin (p = 0.029), low-density lipoprotein cholesterol (p = 0.031), and frequency of cerebrovascular events (p = 0.011). SULF2 rs2281279 showed no association with the studied parameters. The GLCE gene polymorphism rs3865014 appears to have biological relevance in human pathophysiology.

Stop vasodepressor drugs in reflex syncope: a randomised controlled trial

ObjectivesMost elderly patients affected by reflex vasodepressor syncope take one or more hypotensive drugs. The role of these drugs in causing syncope has not yet been established. We hypothesised that...

Brain Infarct and Abscess—A Very Common Disease and a Rare Association

To explore the effectiveness of superficial temporal artery–to–middle cerebral artery (STA-MCA) anastomosis in treating moyamoya disease (MMD).A total of 30 patients with MMD (hemorrhagic type, n = 13; ischemic type, n = 17) who had undergone STA-MCA anastomosis were enrolled in this study (anastomosis group). Cerebral blood flow was evaluated before and after surgery using cerebral angiography and computed tomography (CT) perfusion imaging. In addition, 27 patients with MMD (hemorrhagic type, n = 11; ischemic type, n = 16) who had received only conservative treatment were enrolled as the control group. Patients in both the anastomosis group and the control group were followed up for 5 years, and the incidences of cerebral hemorrhage and cerebral ischemia were analyzed. Blood samples were collected in both groups before and after treatment. Mononuclear cells were separated by density gradient centrifugation. After labeling with 3 direct fluorescent antibodies (CD133, CD34, and vascular endothelial growth factor receptor 2), the number of endothelial progenitor cells (EPCs) was detected using flow cytometry.Cerebral blood flow was remarkably improved after STA-MCA anastomosis. The incidences of cerebral hemorrhage and cerebral ischemia were significantly lower in the anastomosis group than in the control group. The number of EPCs showed no significant change before and after treatment in the control group; in contrast, it was decreased significantly after surgery in the anastomosis group.STA-MCA anastomosis can reduce the number of EPCs in MMD patients, lower the risk of rebreeding, and improve cerebral ischemic attacks.

Failure of Calcineurin Inhibitor (Tacrolimus) Weaning Randomized Trial in Long-Term Stable Kidney Transplant Recipients.

Long-term renal transplant outcome is limited by side effects of immunosuppressive drugs, particularly calcineurin inhibitor (CNI). We assumed that some patients selected for a "low immunological risk of rejection" could be eligible and benefit from a CNI weaning strategy. We designed a prospective, randomized, multicenter, double-blind placebo-controlled clinical study (Eudract: 2010-019574-33) to analyze the benefit-risk ratio of tacrolimus weaning on highly selected patients (≥4 years of transplantation, normal histology, stable graft function, no anti-HLA immunization). The primary endpoint was improvement of renal function. Fifty-two patients were scheduled in each treatment arm, placebo compared to the CNI maintenance arm. Only 10 patients were eligible and randomized. Five patients were assigned to the placebo arm and five were assigned to the tacrolimus maintenance arm. In the tacrolimus maintenance arm, all patients maintained stable graft function and no immunological events occurred. Contrastingly, in the placebo arm, all five patients had to reintroduce a full dose of tacrolimus since three of them presented an acute rejection episode (one humoral, one mixed, and one borderline) and two displayed anti-HLA antibodies without histological lesion (one donor-specific antibodies [DSA] and one non-DSA). Clearly, tacrolimus withdrawal must be avoided even in long-term highly selective stable kidney recipients.

Effectiveness of Superficial Temporal Artery-to-Middle Cerebral Artery Anastomosis in Treating Moyamoya Disease by Reducing Endothelial Progenitor Cells

To explore the effectiveness of superficial temporal artery-to-middle cerebral artery (STA-MCA) anastomosis in treating moyamoya disease (MMD). A total of 30 patients with MMD (hemorrhagic type, n= 13; ischemic type, n= 17) who had undergone STA-MCA anastomosis were enrolled in this study (anastomosis group). Cerebral blood flow was evaluated before and after surgery using cerebral angiography and computed tomography (CT) perfusion imaging. In addition, 27 patients with MMD (hemorrhagic type, n= 11; ischemic type, n= 16) who had received only conservative treatment were enrolled as the control group. Patients in both the anastomosis group and the control group were followed up for 5 years, and the incidences of cerebral hemorrhage and cerebral ischemia were analyzed. Blood samples were collected in both groups before and after treatment. Mononuclear cells were separated by density gradient centrifugation. After labeling with 3 direct fluorescent antibodies (CD133, CD34, and vascular endothelial growth factor receptor 2), the number of endothelial progenitor cells (EPCs) was detected using flow cytometry. Cerebral blood flow was remarkably improved after STA-MCA anastomosis. The incidences of cerebral hemorrhage and cerebral ischemia were significantly lower in the anastomosis group than in the control group. The number of EPCs showed no significant change before and after treatment in the control group; in contrast, it was decreased significantly after surgery in the anastomosis group. STA-MCA anastomosis can reduce the number of EPCs in MMD patients, lower the risk of rebreeding, and improve cerebral ischemic attacks.

Decorin Genotypes, Serum Glucose, Heart Rate, and Cerebrovascular Events: The Tampere Adult Population Cardiovascular Risk Study.

Decorin is an extracellular matrix proteoglycan that may attenuate progression of atherosclerosis and its complications, such as stroke. Among its multitude of functions, decorin has been suggested to serve as a receptor for resistin, an adipokine involved in energy homeostasis. The GG genotype of the decorin polymorphism rs7308752 (A>G) and the CC genotype of the rs516115 (T>C) are associated with decreased plasma resistin levels. The association of the above decorin genotypes with selected cardiometabolic risk factors and cerebrovascular events was studied in the Tampere adult population cardiovascular risk (TAMRISK) study. A Finnish cohort of 336 subjects with diagnosed hypertension and 444 controls was analyzed. Samples were genotyped for decorin rs7308752 and rs516115 polymorphisms using a Competitive Allele-Specific PCR (KASP) technique. Cerebrovascular diseases (I60-I69), including transient cerebral ischemic attacks (G45), were followed up from 2005 to 2014. Subjects with either of decorin rs7308752 genotypes AG/GG had higher serum glucose (p = 0.015) and higher heart rate (p = 0.017) than those with AA genotype. Similarly, decorin rs516115 genotypes TC/CC were associated with higher serum glucose (p = 0.034) and higher frequency of cerebrovascular diseases (p = 0.015) compared to the TT genotype. However, decorin polymorphisms were not associated with hypertension or body mass index. These two decorin polymorphisms appear to have biological relevance in human vascular pathophysiology.

Metabolomic investigation of regional brain tissue dysfunctions induced by global cerebral ischemia.

BackgroundTo get a broader view of global ischemia-induced cerebral disorders at the metabolic level, a nuclear magnetic resonance-based metabolomic study was performed to evaluate the metabolic profile changes on regional brain tissues of female and male mice upon bilateral common carotid arteries occlusion (BCCAO) operation.ResultsSignificant metabolic disorders were observed in both cerebral cortex and hippocampus tissues of the experimental mice upon global cerebral ischemic attack. Multiple amino acids were identified as the dominantly perturbed metabolites. It was also shown that although the metabolic profile change patterns in the brain tissues were quite similar in male and female BCCAO mice, metabolic disorders in the cortex tissues were more severe in the female mice than in the male mice.ConclusionsIn the present study, significant changes in amino acid metabolic pathways were confirmed in the early stage of global ischemia. Meanwhile, cerebral metabolic dysfunctions were more severe in the female BCCAO mice than in the male mice, suggesting that gender may play a role in different metabolic responses to the ischemic attack, which may provide an important hypothesis for a better understanding of the clinically observed gender-dependent pathological outcome of cerebral ischemia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-016-0256-9) contains supplementary material, which is available to authorized users.

Coronary Emboli in a Young Patient with Mechanical Aortic Valve: A Rare Cause of Acute Myocardial Infarction

Coronary artery embolism is an uncommon cause of Acute Myocardial Infarction (AMI). Herein, we reported a 24-year-old male who was admitted with acute inferoposterior myocardial infarction and cerebral Transient Ischemic Attack (TIA). He had undergone mechanical Aortic Valve Replacement (AVR) surgery 6 years ago. Surprisingly, the patient had decided to stop taking his medication (warfarin) 20 days earlier without any medical advice. Coronary angiography revealed a thrombus located at the distal part of the left circumflex artery. Discontinuation of anticoagulant therapy in the presence of mechanical valve prosthesis, clinical evidence of coincidental TIA, and lack of atherosclerotic risk factors were highly suggestive of coronary thromboembolism as the cause of AMI. Overall, this case report emphasized the necessity of continuous education in patients with mechanical heart valves to prevent such undesired events. *Corresponding author: Fereshteh Ghaderi, Atherosclerosis Prevention Research Center, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran, Tel: +98-9151615412, Fax: +98-5138544504, E-mail: drghaderif@yahoo.com

Cryptogenic ischemic stroke and silent atrial fibrillation: What is the relationship?

Atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes and associated with silent cerebral infarctions and transient ischemic attacks. Any method that predicts the stroke or unmasks the silent PAF would contribute to the treatment of ischemic stroke. Intraatrial conduction time (ICT) has been shown to be associated with intermittent AF. In this study, we evaluated the value of ICT detected by transthoracic echocardiography in normal population and in patients with cryptogenic stroke (CS) as a risk factor for stroke. The patients with CS and with normal left ventricular function without valvular disease are included in group 1. Patients with atypical symptoms admitted to cardiology clinics without any risk factor for cardiac disease and found to be normal constituted group 2. Age, gender, weight, height, echocardiographic parameters and ICT were compared between groups. 63 and 64 subjects were included in group 1 and 2, respectively. Two groups were similar according to age and gender. Among the parameters studied, left atrial diameter and height of the patients were significantly higher in group 1 (40 ± 2 vs 37 ± 4 mm, p < 0.001 and 167 ± 9 vs 163 ± 9 cm p = 0.027, respectively). ICT was significantly higher in group 1 (131 ± 15 vs 118 ± 13 ms, respectively, p < 0.000). According to ROC analysis, a cut point of 124 ms for ICT with a sensitivity of 74 % and specificity of 73 % in patients with CS (p < 0.001). This study show us, the measurements the ICT determined by means of echocardiography is longer in patients with CS. This simple and noninvasive technique can be applied widely and lead the clinicians to adopt the use of diagnostic and the treatment procedures.

Cardiovascular events in prostate cancer patients: A comparative analysis of German claims data.

232 Background: In addition to the radical prostatectomy and radiotherapy, androgen deprivation therapies (ADT) have been established as a therapy option in patients with high-risk localized and metastatic prostate cancer (PCa). ADT was found to be associated with a higher risk for cardiovascular (CV) events. This retrospective claims-based study investigated whether CV event rates differ following initiation of ADT with gonadotropin-releasing hormone (GnRH) agonists or antagonists and PCa patients not treated with ADT. Methods: Analyses were based on claims data from the research database of the Health Risk Institute. Eligibility criteria included a PCa diagnosis between 2009 and 2013 and the initiation of ADT with GnRH agonists or antagonists or no ADT during follow up. Outcomes of interest included a composite endpoint of myocardial infarction (MI) or ischemic stroke (IS) as well as the occurrence of a CV event. The latter included MI, sequelae of cerebrovascular disease, IS, intracerebral hemorrhage, pulmonary embolism, phlebitis/thrombophlebitis, transient cerebral ischemic attacks and occlusion/stenosis of cerebral arteries. Results: ADT patients suffered from more comorbidities, were older, and were more likely to suffer from CV conditions than patients with no ADT during baseline. Patients treated with GnRH agonists and antagonists were comparable in terms of mean age and burden of comorbidities. The raw event rates for MI/IS and for CV events during follow up were higher in ADT patients than in patients without ADT (Table 1). Patients treated with GnRH agonists suffered more often from a CV event during follow-up than patients treated with antagonists. Conclusions: Our results indicate that ADT with GnRH antagonists is associated with fewer CV events in PCa patients than treatment with GnRH agonists. The results confirm findings from a pooled analysis of six phase III randomized controlled trials (Albertsen P. et al: Eur Urol 65 (2014) 565-573.). [Table: see text]

Comparison of effects of general anesthesia versus combined epidural-general anesthesia on postoperative complications in patients undergoing thoracic surgery

Objective To compare the effects of general anesthesia versus combined epidural-general anesthesia on postoperative complications in the patients undergoing thoracic surgery. Methods Two hundred twenty-one patients of both sexes, aged 18-80 yr, weighing 36-100 kg, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, scheduled for elective thoracic surgery, were randomly divided into either combined epidural-general anesthesia group(group GE, n=112)or general anesthesia group(group GA, n=109). The patients were further allocated to high-risk population and low-risk population.Anesthesia was induced with target-controlled infusion of remifentanil and iv injection of propofol, sufentanil and rocuronium.A double-lumen endotracheal tube was placed, and the patients were mechanically ventilated.Partial pressure of end-tidal CO2 was maintained at 30-40 mmHg.Anesthesia was maintained with inhalation of 1% sevoflurane, target-controlled infusion of remifentanil, iv infusion of propofol, and intermittent iv boluses of sufentanil.2% lidocaine 4 ml/h was infused epidurally in group GE, and normal saline 4 ml/h was given in group GA.Bispectral index value was maintained at 40-60 during surgery.Patient-controlled epidural analgesia(PCEA)was performed after surgery.PCEA solution contained 0.125% ropivacaine and sufentanil 0.5 μg/ml(in 250 ml of normal saline). The PCEA pump was set up to deliver a 2 ml bolus dose with a 20-min lockout interval and background infusion at 4 ml/h, and visual analogue scale(VAS)score was maintained less than 4.When VAS score ≥ 5, sufentanil 5 μg was injected intravenously as the rescue analgesic.The requirement for rescue analgesics after surgery, length of hospital stay after surgery, complications during postsurgical hospital stay(cardiovascular events, cardiac insufficiency, acute coronary syndrome, pulmonary infection, stroke, transient cerebral ischemic attack), and death within 30 days after surgery were recorded. Results Compared with group GE, the incidence of postsurgical cardiovascular events and atrial fibrillation was significantly decreased in group GA(P 0.05). Conclusion Compared with combined epidural-general anesthesia, general anesthesia alone provides lower occurrence of postsurgical complications for the patients undergoing thoracic surgery, and offers advantage for the high-risk patients having underlying diseases before surgery. Key words: Anesthesia, general; Anesthesia, epidural; Postoperative complications; Thoracic surgical procedures

Excess salt exacerbates blood-brain barrier disruption via a p38/MAPK/SGK1-dependent pathway in permanent cerebral ischemia.

High salt diet (HSD) is one of the most important risk factors that contribute to many vascular diseases including ischemic stroke. One proposed mechanism underlying the disruption of blood-brain barrier (BBB) mediated by HSD is indirectly through enhancing blood pressure. The direct role of HSD on BBB integrity is unclear. Our purpose is to determine whether and how HSD might be involved in BBB breakdown during ischemia. To test that, we induced model of cerebral ischemia by permanent middle cerebral artery ligation (pMCAL) in either normal diet or HSD fed mice. We observed that HSD significantly enhanced ischemic brain damage which was associated with enhanced BBB disruption, increased leukocytes infiltration and loss of tight junction (TJ) proteins expression without apparently altering blood pressure. Our in vitro experiment also revealed that sodium chloride (NaCl) treatment down-regulated TJ protein expression by endothelial cells and substantially increased BBB permeability during starvation. Inhibition of p38/MAPK/SGK1 pathway eliminated the effect of NaCl on BBB permeability in vitro. In addition, we noticed a positive correlation between urinary sodium levels and ischemic lesion size in stroke patients. Together, our study demonstrates a hypertension-independent role of HSD during ischemia and provides rationale for post cerebral ischemic attack management.

Inhibition of TNF-α protects in vitro brain barrier from ischaemic damage.

Cerebral ischaemia, associated with neuroinflammation and oxidative stress, is known to perturb blood-brain barrier (BBB) integrity and promote brain oedema formation. Using an in vitro model of human BBB composed of brain microvascular endothelial cells and astrocytes, this study examined whether suppression of TNF-α, a potent pro-inflammatory cytokine, might attenuate ischaemia-mediated cerebral barrier damage. Radical decreases in transendothelial electrical resistance and concomitant increases in paracellular flux across co-cultures exposed to increasing periods of oxygen-glucose deprivation alone (0.5-20 h) or followed by 20 h of reperfusion (OGD ± R) confirmed the deleterious effects of ischaemic injury on cerebral barrier integrity and function which concurred with reductions in tight junction protein (claudin-5 and occludin) expressions. OGD ± R elevated TNF-α secretion, NADPH oxidase activity, O2(-) production, actin stress fibre formation, MMP-2/9 activities and apoptosis in both endothelial cells and astrocytes. Increases in MMP-2 activity were confined to its extracellular isoform and treatments with OGD+R in astrocytes where MMP-9 could not be detected at all. Co-exposure of individual cell lines or co-cultures to an anti-TNF-α antibody dramatically diminished the extent of OGD ± R-evoked oxidative stress, morphological changes, apoptosis, MMP-2/9 activities while improving the barrier function through upregulation of tight junction protein expressions. In conclusion, vitiation of the exaggerated release of TNF-α may be an important therapeutic strategy in preserving cerebral integrity and function during and following a cerebral ischaemic attack.