Increased levels of F2-isoprostanes following aneurysmal subarachnoid hemorrhage in humans

Subarachnoid hemorrhage (SAH) resulting from aneurysmal rupture is the major cause of nontraumatic SAH. We hypothesized that oxidative stress could be increased following aneurysmal SAH due to hemoglobin release and ischemia-reperfusion injury and that may further contribute to poor outcome. We collected plasma and cerebrospinal fluid (CSF) samples from 11 non-SAH controls and 15 aneurysmal SAH patients for up to 10 days after surgery and investigated status of oxidative stress in patients. Results showed that mean or peak levels of F(2)-isoprostanes (F(2)-IsoPs), a specific marker of lipid peroxidation, and total nitrate/nitrite, metabolites of nitric oxide and peroxynitrite, in CSF and plasma were significantly higher in SAH patients than in controls. First-day levels were also higher in CSF, but not in plasma, in SAH patients. Moreover, mean and peak levels of CSF F(2)-IsoPs were positively correlated with poor outcome or severity of clinical conditions in patients. Furthermore, levels of retinol, delta-tocopherol, beta+gamma-tocopherol, lutein, beta-carotene, and coenzyme Q(10) in plasma were significantly lower in SAH patients than in controls. Our results indicate that oxidative damage may play important roles in the severity and complications of aneurysmal SAH and suggest that means to suppress lipid peroxidation may be beneficial in improving the outcome of aneurysmal SAH.     

Plasma total homocysteine and subarachnoid haemorrhage in a co-factor replete population

Summary. Mild hyperhomocysteinaemia is a postulated risk factor for occlusive vascular disease, including stroke. Subarachnoid haemorrhage (SAH) has an annual incidence of 10–20 per 100,000 and accounts for 5–10% of all strokes. Measurement of plasma total homocysteine (tHcy) in a cohort of vitamin B12 and folate replete patients did not reveal any association between tHcy and the aetiology of SAH. Received November 6, 2000 Accepted February 12, 2001     

Value of positive myocardial infarction imaging in coronary care units.

Positive myocardial imaging was undertaken on 120 unselected patients admitted to a coronary care unit with clinical suspicion of acute myocardial infarction. Multipurpose mobile gamma-cameras were used for serial imaging after administration of 99mtechnetium-labelled imidodiphosphonate, a low-cost radiopharmaceutical that is 97% specific for myocardial necrosis, with myocardial uptake and blood clearance most suitable for myocardial imaging. The sensitivty of detection was 94% for patients whose infarction was unequivocal on the ECG; when the presence of raised enzyme concentrations was also used as a criterion for myocardial necrosis, the overall sensitivity for all 120 patients remained 94%. In 73 patients (61%), whose ECGs were unhelpful or difficult to interpret, scintigraphy allowed infarction to be diagnosed in 11 (15%) and to be excluded in five (7%). In 32 (44%) of this group whose ECGs were totally uninterpretable due to previous myocardial damage or disorders of electrical activation, scintigraphy provided confirmation of a diagnosis that otherwise rested only on whether enzyme concentrations were raised. Myocardial imaging is thus a useful technique that permits more definite diagnosis in patients for whom ECG and enzyme data are uncertain.     

Erythropoietin for the Treatment of Subarachnoid Hemorrhage: A Feasible Ingredient for a Successful Medical Recipe

Subarachnoid hemorrhage (SAH) following aneurysm bleeding accounts for 6% to 8% of all cerebrovascular accidents. Although an aneurysm can be effectively managed by surgery or endovascular therapy, delayed cerebral ischemia is diagnosed in a high percentage of patients resulting in significant morbidity and mortality. Cerebral vasospasm occurs in more than half of all patients after aneurysm rupture and is recognized as the leading cause of delayed cerebral ischemia after SAH. Hemodynamic strategies and endovascular procedures may be considered for the treatment of cerebral vasospasm. In recent years, the mechanisms contributing to the development of vasospasm, abnormal reactivity of cerebral arteries and cerebral ischemia following SAH, have been investigated intensively. A number of pathological processes have been identified in the pathogenesis of vasospasm, including endothelial injury, smooth muscle cell contraction from spasmogenic substances produced by the subarachnoid blood clots, changes in vascular responsiveness and inflammatory response of the vascular endothelium. To date, the current therapeutic interventions remain ineffective as they are limited to the manipulation of systemic blood pressure, variation of blood volume and viscosity and control of arterial carbon dioxide tension. In this scenario, the hormone erythropoietin (EPO) has been found to exert neuroprotective action during experimental SAH when its recombinant form (rHuEPO) is administered systemically. However, recent translation of experimental data into clinical trials has suggested an unclear role of recombinant human EPO in the setting of SAH. In this context, the aim of the current review is to present current evidence on the potential role of EPO in cerebrovascular dysfunction following aneurysmal subarachnoid hemorrhage.     

心肌酶谱、动态心电图及冠状动脉CT血管造影诊断嗜铬细胞瘤儿茶酚胺性心脏损害价值研究

摘要 目的：探讨心肌酶谱、动态心电图及冠状动脉CT血管造影诊断嗜铬细胞瘤儿茶酚胺性心脏损害的临床价值。方法：收集2013年1月-2020年4月在我院诊断为嗜铬细胞瘤患者114例,其中嗜铬细胞瘤儿茶酚胺性心脏损害的患者27例。所有患者均完善术前常规检查（血常规、胸片、动态心电图）、心肌酶谱、心脏超声、冠状动脉CTA等临床资料,并收集患者一般临床资料,如血压、临床症状等。结果：114例嗜铬细胞瘤患者中,27例患者存在嗜铬细胞瘤儿茶酚胺性心脏损害。嗜铬细胞瘤儿茶酚胺性心脏损害患者一般临床资料与嗜铬细胞瘤无儿茶酚胺性心脏损害的患者差异无统计学意义（P＞0.05）。嗜铬细胞瘤儿茶酚胺性心脏损害以高血压为主要表现,临床症状表现多样,可伴有头痛、心悸、多汗三联征表现。114例患者中,26例患者出现心肌酶谱升高,36例患者存在不同程度的心电图异常、24例患者冠状动脉CTA异常,嗜铬细胞瘤儿茶酚胺性心脏损害患者在心肌酶谱、动态心电图及冠状动脉CTA异常例数与嗜铬细胞瘤无儿茶酚胺性心脏损害患者中差异均有统计学意义（P＜0.05）。114例患者中心肌酶谱或心电图或冠状动脉CTA异常的患者总共56例,其中嗜铬细胞瘤儿茶酚胺性心脏损害患者23例,嗜铬细胞瘤无儿茶酚胺性心脏损害患者有33例,差异有统计学意义（P＜0.05）。嗜铬细胞瘤儿茶酚胺性心脏损害患者中,心律失常最为常见。结论：嗜铬细胞瘤儿茶酚胺性心脏损害患者心肌酶谱、动态心电图及冠状动脉CTA均可存在异常表现,但特异性、敏感性不高,三者同时综合分析可以提高临床诊断。     

The autophagy–lysosomal system in subarachnoid haemorrhage

The autophagy–lysosomal pathway is a self‐catabolic process by which dysfunctional or unnecessary intracellular components are degraded by lysosomal enzymes. Proper function of this pathway is critical for maintaining cell homeostasis and survival. Subarachnoid haemorrhage (SAH) is one of the most devastating forms of stroke. Multiple pathogenic mechanisms, such as inflammation, apoptosis, and oxidative stress, are all responsible for brain injury and poor outcome after SAH. Most recently, accumulating evidence has demonstrated that the autophagy–lysosomal pathway plays a crucial role in the pathophysiological process after SAH. Appropriate activity of autophagy–lysosomal pathway acts as a pro‐survival mechanism in SAH, while excessive self‐digestion results in cell death after SAH. Consequently, in this review article, we will give an overview of the pathophysiological roles of autophagy–lysosomal pathway in the pathogenesis of SAH. And approaching the molecular mechanisms underlying this pathway in SAH pathology is anticipated, which may ultimately allow development of effective therapeutic strategies for SAH patients through regulating the autophagy–lysosomal machinery.     

Electrocardiographic changes during exercise in asymptomatic men: 3-year follow-up.

Electrocardiographic (ECG) changes during maximal bicycle exercise and risk factors for coronary heart disease (CHD) were studied in 510 male civic employees who were followed for 3 years. Clinical CHD developed in 15 (24.6 percent) of the 61 men with an ischemic exercise ECG on the initial examination and in 11 (2.4 percent) of the 449 subjects with a normal initial exercise ECG. A normal maximal exercise ECG is no guarantee that severe CHD does not exist and that a subject will not soon sustain major myocardial damage; and an ischemic exercise ECG does not necessarily indicate underlying CHD. In the former group angina was the most frequent clinical CHD episode; in the latter group, infarction. Among those with an abnormal initial exercise ECG, CHD was most likely to develop in association with a poor exercise capacity. Subjects with subsequent clinical CHD and those with abnormal ECGs after 3 years tended to have a higher frequency of risk factors; subjects whose abnormal ECGs reverted to normal after 3 years tended to have a lower frequency of risk factors.     

The role and therapeutic potential of heat shock proteins in haemorrhagic stroke

Heat shock proteins (HSPs) are induced after haemorrhagic stroke, which includes subarachnoid haemorrhage (SAH) and intracerebral haemorrhage (ICH). Most of these proteins function as neuroprotective molecules to protect cerebral neurons from haemorrhagic stroke and as markers to indicate cellular stress or damage. The most widely studied HSPs in SAH are HSP70, haeme oxygenase‐1 (HO‐1), HSP20 and HSP27. The subsequent pathophysiological changes following SAH can be divided into two stages: early brain injury and delayed cerebral ischaemia, both of which determine the outcome for patients. Because the mechanisms of HSPs in SAH are being revealed and experimental models in animals are continually maturing, new agents targeting HSPs with limited side effects have been suggested to provide therapeutic potential. For instance, some pharmaceutical agents can block neuronal apoptosis signals or dilate cerebral vessels by modulating HSPs. HO‐1 and HSP70 are also critical topics for ICH research, which can be attributed to their involvement in pathophysiological mechanisms and therapeutic potential. However, the process of HO‐1 metabolism can be toxic owing to iron overload and the activation of succedent pathways, for example, the Fenton reaction and oxidative damage; the overall effect of HO‐1 in SAH and ICH tends to be protective and harmful, respectively, given the different pathophysiological changes in these two types of haemorrhagic stroke. In the present study, we focus on the current understanding of the role and therapeutic potential of HSPs involved in haemorrhagic stroke. Therefore, HSPs may be potential therapeutic targets, and new agents targeting HSPs are warranted.     

Subclinical myocardial infarction presenting as free wall rupture

A 50-year-old man presented twice within a period of two weeks with symptoms and electrocardio-graphic (ECG) findings suggesting postinfarct angina. The ECG showed sinus tachycardia with Q waves, ST-segment elevation and terminally negative T waves in lead II, III and aVF, suggesting remote inferior myocardial infarction. During the first hospitalisation the ECG also showed signs of pericarditis. Troponin I levels were only slightly elevated. Echocardiographic evaluation at the second presentation demonstrated a posterolateral false aneurysm following ischaemic left ventricular rupture (figure 1).     

Molecular pathogenesis of subarachnoid haemorrhage

Subarachnoid haemorrhage (SAH) results from leakage of blood into the subarachnoid space and carries high morbidity and mortality. However, there is limited understanding to date, of the risk factors, cellular, intermediate biochemical and genetic traits predisposing to SAH. Nevertheless, in conjunction with improved methods of diagnostic imaging and less invasive approaches to preventing aneurysmal rupture, there may be utility in gaining a better understanding of the pathogenesis and in identifying pre-disease markers. Additionally, it is not impossible that drugs of value (e.g. matrix or endothelial modifiers) could become available. Several different clinical subtypes can be recognised, distinguished by arterial or venous involvement, presence of unruptured arterial aneurysms, and apparently "sporadic" and "familial" occurrences. Epidemiological risk factors include alcohol consumption and smoking: hypertension is a risk factor for rupture. About 10% seem to reflect strong family history and this subset may be particularly illuminating with respect to the molecular pathogenesis. Haemodynamic stress and poor vascular structure may be the main mechanisms of pathogenesis. The epidemiological and statistical evidence for familial megaphenic genes and modifier genes is reviewed. This review focuses on the pathogenesis, as opposed to inflammatory response to SAH. It sets in context the roles of specific genes and their protein products, such as polycystin (PKD1), fibrillin (FBN1), collagen III (COL3A1), elastin (ELN), collagen IV, protease inhibitor or alpha1-antitrypsin (PI) and proteases. These considerations illustrate the shortfalls in current knowledge, the needs of future biochemical and cellular research and their potential implications for future prevention of this often fatal condition.     

Protein phosphorylation studies of cerebral spinal fluid for potential biomarker development

Subarachnoid hemorrhage (SAH) followed by cerebral vasospasm (CV) leads to severe debilitation or death of an estimated one million people worldwide every year. A biomarker that would predict the onset of CV after a SAH would be useful in informing treatment protocols, but has yet to be found. The focus of this study is to explore differences in protein phosphorylation in cerebral spinal fluid (CSF) among healthy patients, SAH patients and SAH-CV patients. A significant difference in phosphorylation among the three sample types could be an important step towards the discovery of a diagnostic marker. The identification and validation of phosphorylated protein differences for study is manifested in the nature of signaling involved in the pathological events seen post SAH. Capillary liquid chromatography (cap-LC) coupled to inductively coupled plasma mass spectrometry (ICPMS) and nano-liquid chromatography-CHIP/ion trap mass spectrometry (nanoLC-CHIP/ITMS) are used to identify and measure protein phosphorylation changes in the CSF of the aforementioned groups. ICPMS represents a suitable method for screening ultra-trace phosphorus levels at the natural isotope, (31)P, while nano-LC-CHIP/ITMS is used to identify phosphoproteins by searching appropriate protein databases.     

Progressive DNA and RNA damage from oxidation after aneurysmal subarachnoid haemorrhage in humans

Free radical toxicity is considered as a key mechanism in the neuronal damage occurring after aneurysmal subarachnoid haemorrhage (SAH). We measured markers of DNA and RNA damage from oxidation (8-oxodG and 8-oxoGuo, respectively) in cerebrospinal fluid from 45 patients with SAH on day 1–14 after ictus and 45 age-matched healthy control subjects. At baseline, both markers were significantly increased in patients compared to controls (p values?20-fold above control levels) from day 5–14. None of the markers predicted the occurrence of vasospasms or mortality, although there was a trend that the 8-oxoGuo marker was more strongly associated with mortality than the 8-oxodG marker. We conclude that SAH leads to a massive increase in damage to nucleic acids from oxidative stress, which is likely to play a role in neuronal dysfunction and death. As only patients in need of a ventriculostomy catheter were included in the study, the findings cannot necessarily be extrapolated to all patients with SAH.     

Elevated hepatic iron: A confounding factor in chronic hepatitis C

Historically, iron overload in the liver has been associated with the genetic disorders hereditary hemochromatosis and thalassemia and with unusual dietary habits. More recently, elevated hepatic iron levels also have been observed in chronic hepatitis C virus (HCV) infection. Iron overload in the liver causes many changes including induction of oxidative stress, damage to lysosomes and mitochondria, altered oxidant defense systems and stimulation of hepatocyte proliferation. Chronic HCV infection causes numerous pathogenic changes in the liver including induction of endoplasmic reticulum stress, the unfolded protein response, oxidative stress, mitochondrial dysfunction and altered growth control. Understanding the molecular and cellular changes that could occur in a liver which has elevated hepatic iron levels and in which HCV replication and gene expression are ongoing has clinical relevance and represents an area of research in need of further investigation.     

MicroRNA-26b/PTEN Signaling Pathway Mediates Glycine-Induced Neuroprotection in SAH Injury

Neurochemical Research - Subarachnoid hemorrhage (SAH) is a form of stroke associated with high mortality and morbidity. Despite advances in treatment for SAH, the prognosis remains poor. We have...     

Pterostilbene Attenuates Early Brain Injury Following Subarachnoid Hemorrhage via Inhibition of the NLRP3 Inflammasome and Nox2-Related Oxidative Stress

Pterostilbene (PTE), one of the polyphenols present in plants such as blueberries and grapes, has been suggested to have various effects, such as anti-oxidation, anti-apoptosis, and anti-cancer effects. Subarachnoid hemorrhage (SAH) is a severe neurological event known for its high morbidity and mortality. Recently, early brain injury (EBI) has been reported to play a significant role in the prognosis of patients with SAH. The present study aimed to investigate whether PTE could attenuate EBI after SAH was induced in C57BL/6 J mice. We also studied possible underlying mechanisms. After PTE treatment, the neurological score and brain water content of the mice were assessed. Oxidative stress and neuronal injury were also evaluated. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activity was assessed using western blot analysis. Our results indicated that PTE treatment reduces the SAH grade, neurological score, and brain water content following SAH. PTE treatment also reduced NLRP3 inflammasome activation. PTE alleviated the oxidative stress following SAH as evidenced by the dihydroethidium staining, superoxide dismutase activity, malondialdehyde content, 3-nitrotyrosie and 8-hydroxy-2-deoxyguanosine levels, and gp91^phox and 4-hydroxynonenal expression levels. Additionally, PTE treatment reduced neuronal apoptosis. In conclusion, our study suggests that PTE attenuates EBI following SAH possibly via the inhibition of NLRP3 inflammasome and Nox2-related oxidative stress.     

e-Transmission of ECGs for expert consultation results in improved triage and treatment of patients with acute ischaemic chest pain by ambulance paramedics

Aims

In pre-hospital settings handled by paramedics, identification of patients with myocardial infarction (MI) remains challenging when automated electrocardiogram (ECG) interpretation is inconclusive. We aimed to identify those patients and to get them on the right track to primary percutaneous coronary intervention (PCI).

Methods and results

In the Rotterdam-Rijnmond region, automated ECG devices on all ambulances were supplemented with a modem, enabling transmission of ECGs for online expert interpretation. The diagnostic protocol for acute chest pain was modified and monitored for 1 year.Patients with an ECG that met the criteria for ST-elevation myocardial infarction (STEMI) were immediately transported to a PCI hospital. ECGs that did not meet the STEMI criteria, but showed total ST deviation ≥800?µv were transmitted for online interpretation by the ECG expert. Online supervision was offered as a service if ECGs showed conduction disorders, or had an otherwise ‘suspicious’ pattern according to the ambulance paramedics.We enrolled 1,076 patients with acute ischaemic chest pain who did not meet the automated STEMI criteria. Their mean age was 63 years; 64% were men. After online consultation, 735 (68%) patients were directly transported to a PCI hospital for further treatment. PCI within 90?min was performed in 115 patients.

Conclusion

During a 1-year evaluation of the modified pre-hospital triage protocol for patients with acute ischaemic chest pain, over 100 acute MI patients with an initially inconclusive ECG received primary PCI within 90?min. Because of these results, we decided to continue the operation of the modified protocol.

     

正常人体表心电图形态的逐拍变化

心电图的各种波形是众多心肌细胞动作电位在体表的综合效应。建立了对体表心电图的形态进行逐拍分析的硬件及软件系统。对５８例健康人体表心电图进行了采集和分析,得到了正常人体表心电图中Ｐ波,ＱＲＳ波,及Ｔ波的形态差异图,并进行了频谱及时域瞬态分析,从而展示了心肌电活动在体表心电图中的逐拍变化现象,体表心电图逐拍形态变化反映了心房肌和心室肌电活动的时变特征。     

Knock-Down of CD24 in Astrocytes Aggravates Oxyhemoglobin-Induced Hippocampal Neuron Impairment

Neurochemical Research - Subarachnoid hemorrhage (SAH), as one of the most severe hemorrhagic strokes, is closely related to neuronal damage. Neurogenesis is a promising therapy, however, reliable...     

Usefulness of three additional electrocardiographic chest leads (V7, V8, and V9) in the diagnosis of acute myocardial infarction.

Additional electrocardiocardiographic chest leads (V7, V8, and V9) were used in 117 persons consecutively admitted to a coronary care unit. Among the 46 (39%) with a proven acute myocardial infarction the electrocardiograms (ECGs) of 9 (20%) showed ST-segment elevation or abnormal Q-waves, or both, in the three additional leads. In six of the nine, such changes were associated with signs of anterolateral or inferior wall infarction (in three each) on the standard 12-lead ECG, but in the other three (7% of the 46) electrocardiographic changes diagnostic of acute myocardial infarction were found only on the additional chest leads; the last three had characteristic changes in serum enzyme concentrations. This study showed that additional chest leads are helpful in detecting myocardial injury of necrosis in areas of the heart not properly reflected on the standard 12-lead ECG.