Current advances in the understanding of coronary vasospasm

Recent years have witnessed progress in our understanding of coronary vasospasm(CVS).It is evident that this is not only an East Asian but also a global disease associated with significant symptoms and possible lethal sequelae for afflicted individuals.A correct diagnosis depends on the understanding of pathogenesis and symptomatology of CVS.With the correct diagnosis,we can manage CVS patients effectively and promptly,providing optimal patient safety.Advances in our understanding of interactions between inflammation,endothelium,and smooth muscle cells have led to substantial progress in understanding the pathogenesis of symptoms in CVS and have provided some insights into the basic etiology of this disorder in some patient subpopulations.We look forward to a time when therapy will address pathophysiology and perhaps,even the primary etiology.

Cardiorenal syndromes

Cardiorenal syndromes (CRS) have been subclassified as five defined entities which represent clinical circumstances in which both the heart and the kidney are involved in a bidirectional injury and dysfunction via a final common pathway of cell-to-cell death and accelerated apoptosis mediated by oxidative stress. Types 1 and 2 involve acute and chronic cardiovascular disease (CVD) scenarios leading to acute kidney injury or accelerated chronic kidney disease. Types 2 and 3 describe acute and chronic kidney disease leading primarily to heart failure, although it is possible that acute coronary syndromes, stroke, and arrhythmias could be CVD outcomes in these forms of CRS. Finally, CRS type 5 describes a simultaneous insult to both heart and kidneys, such as sepsis, where both organs are injured simultaneously. Both blood and urine biomarkers are reviewed in this paper and offer a considerable opportunity to enhance the understanding of the pathophysiology and known epidemiology of these recently defined syndromes.

Marked elevation of B-type natriuretic peptide in patients with heart failure and preserved ejection fraction

Marked elevations of B-type natriuretic peptide （BNP） are not generally seen in patients with heart failure and preserved ejection fraction （HFpEF）. The objective of this study was to examine the clinical and laboratory characteristics of a large cohort of patients with HFpEF and markedly elevated BNP. A retrospective examination of 421 inpatients at a university hospital admitted with a diagnosis of HFpEF was performed. Clinical and echocardiographic data in 4 groups of patients with levels of BNP ≤ 100 pg/mL, 100-400 pg/mL, 400-1,000 pg/mL and 〉 1,000 pg/mL were compared. Patients with HFpEF and BNP 〉 1,000 pg/mL （28% of the population） were characterized by impaired renal function and greater use of anti-hypertensive medications. A subset of these patients with BNP 〉 1,000 pg/mL had normal renal function （21%） and were significantly older, more frequently female, and tended to have lower ejection fractions. Conversely, patients with HFpEF and BNP ≤100 pg/mL were younger and had preserved renal function. BNP was inversely related to the likelihood of subsequent admission for heart failure, but not to myocardial infarction or death. In conclusion： BNP 〉 1,000 pg/mL is seen in almost 1/3 of patients hospitalized with HFpEF. This elevation of BNP often reflects impaired renal function, but can also be seen in patients with preserved renal function but relatively impaired systolic function.

Who benefits from percutaneous closure of patent foramen ovale vs medical therapy for stroke prevention? In-depth and updated metaanalysis of randomized trials

BACKGROUND A few randomized clinical trials(RCT) and their meta-analyses have found patent foramen ovale closure(PFOC) to be beneficial in prevention of stroke compared to medical therapy. Whether the benefit is extended across all groups of patients remains unclear.AIM To evaluate the efficacy and safety of PFOC vs medical therapy in different groups of patients presenting with stroke, we performed this meta-analysis of RCTs.METHODS Electronic search of PubMed, EMBASE, Cochrane Central, CINAHL and ProQuest Central and manual search were performed from inception through September 2018 for RCTs. Ischemic stroke(IS), transient ischemic attack(TIA), a composite of IS, TIA and systemic embolism(SE), mortality, major bleeding,atrial fibrillation(AF) and procedural complications were the major outcomes.Random-effects model was used to perform analyses.RESULTS Meta-analysis of 6 RCTs including 3560 patients showed that the PFOC,compared to medical therapy reduced the risk of IS [odds ratio: 0.34; 95%confidence interval: 0.15-0.78; P = 0.01] and the composite of IS, TIA and SE [0.55(0.32-0.93); P = 0.02] and increased the AF risk [4.79(2.35-9.77); P < 0.0001]. No statistical difference was observed in the risk of TIA [0.86(0.54-1.38); P = 0.54],mortality [0.74(0.28-1.93); P = 0.53] and major bleeding [0.81(0.42-1.56); P = 0.53]between two strategies. Subgroup analyses showed that compared to medical therapy, PFOC reduced the risk of stroke in persons who were males, ≤ 45 years of age and had large shunt or atrial septal aneurysm.CONCLUSION In certain groups of patients presenting with stroke, PFOC is beneficial in preventing future stroke compared to medical therapy.

Dyslipidemia： evidence of efficacy of the pharmacological and non-pharmacological treatment in the elderly

为心血管的疾病(CVD ) 控制风险因素在的临床的决定老考虑下列：(1 ) 老预期寿命；(2 ) 老生物年龄和功能的能力；(3 ) 在老组的心血管的疾病的角色；(4 ) 风险因素在的流行老；并且(5 ) 风险因素在的治疗的有效性老。很多研究显示出 dyslipidemia 的第二等、主要的预防的功效在老。然而，在 80 年包括了病人的唯一的审判是心保护学习(HPS ) 。Statins 为阴沉的低密度的脂蛋白胆固醇(LDL-C ) 被认为第一线治疗。因为生活方式变化是很困难的完成，医生们一般来说趋于开许多药控制心血管的风险因素。然而，健康食物消费在主要、第二等的心血管的预防仍然是一块奠基石并且应该被每个人实现。

Intermediate-term mortality and incidence of ICD therapy in octogenarians after cardiac resynchronization therapy

在超过 80 岁的病人的心脏的再同步治疗(CRT ) 的 BackgroundClinical 结果一直不是回顾地识别的井 described.MethodsWe 96 连续病人 &#x02265；80 岁经历了一起始植入或升级到 CRT，与或没有使用高压脉冲来消减心脏(CRT-D 对 CRT-P ) ，在我们在 2003 年 1 月和 2008 年 7 月之间的机构。控制队由 177 随机选择的病人 &#x0003c 组成了；经历 CRT 的 80 岁在一样的时间时期期间植入。主要功效端点是在 36 个月的所有原因死亡，到第一事件 curves.ResultsIn 的 Kaplan-Meier 时间估计了八十至八十九岁的队，在 CRT 的吝啬的年龄植入是 83.1 &#x000b1；2.9 年对 60.1 &#x000b1；在控制之中的 8.8 年(P &#x0003c；0.001 ) 。越过两个组， 70% 是男性的，吝啬的左室的喷射部分(LVEF ) 是 24.8%&#x000b1；14.1% 并且 QRS 持续时间是 154 &#x000b1；24.8 ms，没有组之间的重要差别。Octogenarians 是更可能的有 ischemic 心肌症(74% 对 37% ， P &#x0003c；0.001 ) 并且可能经历的更多升级到 CRT 而不是一起始植入(42% 对 19% ， P &#x0003c；0.001 ) 。适当使用高压脉冲来消减心脏震动的率在 octogenarians 之中是更低的(14% 对 27% ， P = 0.02 ) 而不恰当的震动的率是类似的(3% 对 6% ， P = 0.55 ) 。在 36 个月，处于在 octogenarians (11%) 和控制之间的所有原因死亡的率没有重要差别(8% ， P = 0.381 ).ConclusionAppropriately 选择的 octogenarians 是 CRT 的候选人与收到 CRT 的更年轻的病人相比有类似的中间术语的死亡。

Contemporary characteristics and outcomes of adults with familial dilated cardiomyopathy listed for heart transplantation

BACKGROUND Familial dilated cardiomyopathy(FDCM) account for 20%-30% of non-ischemic cardiomyopathies(NICM). Previous published data showed that some patients with FDCM tend to have rapidly progressive disease; however, five-year mortality was not significantly different in the familial and non-familial forms of NICM with optimal medical therapy.AIM To better define the characteristics and clinical outcomes of FDCM patients listed for heart transplantation(HT).METHODS We queried the United Network for Organ Sharing Registry to identify FDCM patients listed for HT between January 2008 and September 2015 and compared them to NICM and ischemic cardiomyopathy(ICM) patients. We included all patients ≥ 18 years old and we separated patients to three groups: FDCM, NICM and ICM. Chi-square test was used to compare between categorical variables, the t-test was used to compare between continues variables, and Cox-proportional hazards model was used to perform time-dependent survival analyses.RESULTS Of the 24809 adults listed for HT, we identified 677 patients(2.7%) with the diagnosis of FDCM. Compared to patients with NICM and ICM, FDCM patients were younger(FDCM 43.9 ± 13.5 vs NICM 50.9 ± 12.3, P < 0.001, vs ICM 58.5 ±8.1, P < 0.001), more frequently listed as status 2(FDCM 35.2% vs NICM 26.5%, P< 0.001), with significantly lower left ventricular assist device(LVAD) utilization(FDCM 18.4% vs NICM 25.1%, P < 0.001; vs ICM 25.6%, P < 0.001), but higher use of total artificial heart(FDCM 1.3% vs NICM 0.6%, P = 0.039; vs ICM 0.4%, P =0.002). Additionally, patients with FDCM were less frequently delisted for clinical deterioration or death and more likely to be transplanted compared to those with NICM [hazard ratio(HR): 0.617, 95% confidence interval(CI): 0.47-0.81; HR: 1.25,95%CI: 1.14-1.37, respectively], and ICM(HR: 0.5, 95%CI: 0.38-0.66; HR: 1.18,95%CI: 1.08-1.3, respectively). There was more frequent rejection among patients with FDCM(FDCM 11.4% vs NICM 9.8%, P = 0.28; vs ICM 8.4%, P = 0.034). One,three, and five post-transplant survival of patients with FDCM(91%, 88% and80%) was similar to those with NICM(91%, 84%, 79%, P = 0.225), but superior to those with ICM(89%, 82%, 75%, P = 0.008), respectively.CONCLUSION End-stage FDCM patients are more likely to be transplanted, more likely to have early rejection, and have similar or higher survival than patients with other cardiomyopathies.

The subcutaneous implantable cardioverter defibrillator—— review of the recent data

下的可植入的 cardioverter 使用高压脉冲来消减心脏(SICD ) 是为突然的心脏的死亡(SCD ) 的预防的 transvenous ICD 的一种选择。多重研究证明了 SICD 在对待室的心律不齐安全、有效。当更早的研究主要与 channelopathies 注册了更年轻的病人时，更最近的报告为 SCD 的预防为 ICD 治疗与典型指示包括了病人。在这评论，我们总结可得到的数据当加亮它的利弊时，在 SICD 上标明日期。

Heart disease in Friedreich's ataxia

Friedreich's ataxia(FRDA), which occurs in 1/50000 live births, is the most prevalent inherited neuromuscular disorder. Nearly all FRDA patients develop cardiomyopathy at some point in their lives. The clinical manifestations of FRDA include ataxia of the limbs and trunk, dysarthria, diabetes mellitus, and cardiac diseases. However, the broad clinical spectrum makes FRDA difficult to identify.The diagnosis of FRDA is based on the presence of suspicious clinical factors, the use of the Harding criteria and, more recently, the use of genetic testing for identifying the expansion of a triplet nucleotide sequence. FRDA is linked to a defect in the mitochondrial protein frataxin; an epigenetic alteration interferes with the folding of this protein, causing a relative deficiency of frataxin in affected patients. Frataxins are small essential proteins whose deficiency causes a range of metabolic disturbances, including oxidative stress, iron-sulfur cluster deficits, and defects in heme synthesis, sulfur amino acid metabolism, energy metabolism, stress responses, and mitochondrial function. The cardiac involvement seen in FRDA is a consequence of mitochondrial proliferation as well as the loss of contractile proteins and the subsequent development of myocardial fibrosis. The walls of the left ventricle become thickened, and different phenotypic manifestations are seen, including concentric or asymmetric hypertrophy and(less commonly) dilated cardiomyopathy. Dilated cardiomyopathy and arrhythmia are associated with mortality in patients with FRDA, whereas hypertrophic cardiomyopathy is not. Systolic function tends to be low-normal in FRDA patients, with an acute decline at the end of life.However, the literature includes only a few long-term prospective studies of cardiac progression in FRDA, and the cause of death is often attributed to heart failure and arrhythmia postmortem. Cardiomyopathy tends to be correlated with the clinical neurologic age of onset and the nucleotide triplet repeat length(i.e.,markers of phenotypic disease severity) rather than the duration of disease or the severity of neurologic symptoms. As most patients are wheelchair-bound within15 years of diagnosis, the clinical determination of cardiac involvement is often complicated by comorbidities. Researchers are currently testing targeted therapies for FRDA, and a centralized database, patient registry, and natural history study have been launched to support these clinical trials. The present review discusses the pathogenesis, clinical manifestations, and spectrum of cardiac disease in FRDA patients and then introduces gene-targeted and pathology-specific therapies as well as screening guidelines that should be used to monitor cardiac disease in this mitochondrial disorder.

Atherosclerotic plaque burdens in type 2 diabetes

In this issue of the Journal of Geriatric Cardiology,Huang et al. have reported the detection of coronary artery disease with electron-beam computed tomography (EBCT),utilizing non-contrast and contrast imaging techniques (EBCTA) in several subgroups including type 2 diabetes mellitus (DM), impaired glucose tolerance (IGT), coronary heart disease, and normal subjects. ……

Renin and cardiovascular disease:Worn-out path,or new direction?

Inhibition of the renin angiotensin system has beneficial effects in cardiovascular prevention and treatment. The advent of orally active direct renin inhibitors adds a novel approach to antagonism of the renin-angiotensin system.Inhibition of the first and rate-limiting step of the renin angiotensin cascade offers theoretical advantages over downstream blockade.However,the recent discovery of the(pro)renin receptor which binds both renin and prorenin,and which can not only augment catalytic activity of both renin and prorenin in converting angiotensinogen to angiotensinⅠ,but also signal intracellularly via various pathways to modulate gene expression,adds a significant level of complexity to the field.In this review,we will examine the basic and clinical data on renin and its inhibition in the context of cardiovascular pathophysiology.

Continuous Flow Left Ventricular Assist Device Therapy:A Focused Review on Optimal Patient Selection and Long-Term Follow-up Using Echocardiography

Despite widespread awareness and use of scientifi cally proven life-prolonging medical and device-based therapies over the last two decades,heart failure remains a leading cause of morbidity,mortality,and health care expenditure in the United States.Mechanical circulatory support with a continuous-fl ow left ventricular assist device(CF-LVAD),either as a bridge to heart transplantation or as destination therapy,is an increasingly used treatment modality for patients with advanced heart failure syndromes that worsen despite their receiving standard therapies.CF-LVAD support creates unique hemodynamic alterations that must be understood to provide appropriate care for these patients before and after implantation.Echocardiography is essential in the evaluation of patients who are being considered for or are mechanically supported by CF-LVADs.Here we provide a focused clinical review on the use of echocardiography in two main aspects of the evaluation of these patients:(a)optimal patient selection for CF-LVAD support and(b)followup assessment of optimal pump function.

Stent,drug,polymer——enefits,risks,and opportunities

It has been well established that use of drug-eluting stents has resulted in marked reduction in neointimal proliferation following stenting and that this is reflected clinically in a very significant decrease in late lumen loss, instent restenosis, and target lesion revascularization. This benefit occurs, however, in the setting of delayed endothelial and vascular wall healing with its potential for continuing thrombogenicity requiring more prolonged use of dual antiplatelet therapy to prevent stent thrombosis.……

Gadolinium enhanced MRI in patients with left ventricular apical ballooning syndrome implicates myocarditis as an etiology

Aims: Left ventricular apical ballooning syndrome (LVABS) is a clinical condition of unknown etiology, characterized by acute onset of atypical apical wall motion and absence of coronary artery disease. Gadolinium-enhanced cardiac magnetic resonance imaging (Gd-MRI) may be used to identify patients with myocarditis. Using cardiac MRI, we evaluated whether acute myocarditis may be an etiology that underlies LVABS. Methods and Results: Consecutive patients who presented with LVABS during a three-year period were included. Demographic data was recorded and echocardiography, coronary angiography, and hemodynamic assessment performed. Gd-MRI was performed in all patients. The study was deemed consistent with myocarditis when global myocardial to skeletal muscle enhancement ratio was ≥3.5. Regional Gd-MRI analysis was also performed. Patients (n = 11) were female (100%) and of mean age 72 years (72 ± 11). Preceding febrile illness occurred in 4 (36.3%) and leukocytosis in 6 (54.4%) patients. Initial mean left ventricular ejection fraction (41% ± 12%) improved (70.2% ± 8%) upon follow-up (39 ± 43 days). Global MRI analysis was positive in 5/11 (45.5%) (mean relative enhancement ratio 4.8 ± 1.4). Regional MRI analysis was positive in 4/6 further patients (overall: 9/11 (82%)). Conclusions: Gadolinium enhanced MRI imaging in LVABS implicates myocarditis as a possible etiology. Regional MRI analysis adds sensitivity to global cardiac MRI evaluation.

Fast Track Extubation Post Coronary Artery Bypass Graft: A Retrospective Review of Predictors of Clinical Outcomes

Introduction: Fast track (FT) cardiac surgery and early extubation (EE) are aimed at safe and effective rapid post-operative progression to discharge, and have been practiced for more than two decades. Their goal is to optimize patient care perioperatively in order to decrease costs without negatively affecting morbidity and mortality. However, the factors that predict successful EE are poorly understood, and patients with significant co-morbidities are frequently excluded from protocols. We hypothesize that independent of disease severity, early extubation leads to shorter hospital stays and can be performed safely without negatively affecting outcomes. Materials and Methods: We performed a retrospective review of 919 patients who underwent coronary artery bypass grafting (CABG) at the Southern Arizona Veteran’s Affairs Health Care System medical center over 7 years. We collected pre-operative data regarding patients’ NYHA classification, presence and severity of cerebral vascular disease, peripheral vascular disease, pulmonary disease, diabetes and hypertension. Intra-operative variables were also recorded including ASA scores, ischemic times, and time to extubation. Finally, post-operative variables such as rates of reintubation and tracheotomy, and both length of ICU and total hospital stay were also compared. Results: Prolonged periods of ischemia were found to predict a delayed extubation (HR = 0.992;CI = 0.988 - 0.997, p = 0.0015) while small body surface area (HR = 1.57;CI = 1.13, 2.17, p = 0.007) and higher pre-operative functional status of the patient, such as independent versus dependent status (HR =1.68;CI = 1.30 - 2.16, p = 1.33;CI = 1.03 - 1.70, p = 0.03) were found to be associated with earlier extubation. The early extubation (EE) group (those extubated in less than the median 7.3 hours) had an average hospital stay of 5.1 ± 4.0 days, versus 7.8 ± 8.1 days in the delayed group (>4 hours), p Conclusions: In our study population, pre-operative functional class and total body surface area predicted those patients able to tolerate early extubation after cardiac surgery. Prolonged ischemia resulted in delayed extubation. Patients that were extubated in less than 4 hours had shorter ICU and hospitalization stays, while there was no significant difference between the two groups in rate of reintubation or tracheotomy.

术前白细胞计数与隐静脉移植物经皮冠状动脉介入治疗后主要不良心血管事件

Elevation of white blood cells(WBCs) is associated with worse outcomes in patients with coronary artery disease(CAD), including patients undergoing percutaneous coronary intervention(PCI) of native coronary arteries, but this relation has not been studied in patients with saphenous vein graft disease undergoing PCI. A total of 530 patients who underwent PCI of saphenous vein grafts from May 1997 to July 2002 were followed for >3 years. Major adverse coronary events(MACEs) were assessed as a composite of death, myocardial infarction, or revascularization during follow-up(mean 2.7 years). Patients with MACEs(n=287) were younger and had more thrombotic and ostial lesions(p< 0.05) than those without MACEs(n=243). The preprocedural WBC count was also significantly higher in the MACE group than in the non-MACE group(8.1×103/μl, range 6.6 to 10.1, vs 7.0×103/μl, range 5.6 to 8.2; p< 0.001). After adjusting for covariates, multiple logistic regression analysis revealed the preprocedural WBC count to be an independent predictor for MACEs(odds ratio 1.2; 95%confidence interval 1.1 to 1.3, p< 0.001). Patients in the highest quartile of the preprocedural WBC level had a significantly increased risk of MACEs(lowest vs highest quartile, 41.3%vs 72.4%; odds ratio 3.7; 95%confidence interval 2.2 to 6.3). Thus, an elevated preprocedural WBC count is associated with increased risk of MACEs in patients undergoing PCI for saphenous vein graft lesions.

不同脂质指标预测男女人群冠心病的临床作用

背景：对于载脂蛋白与传统脂质测量指标预测冠心病（coronaryheartdisease，CHD）危险的性能，目前有关证据尚有矛盾。 目的：采用鉴别和标准化特征（discrimination and calibration characteristics）以及危险再分类对不同脂质测量指标预测CHD的性能进行比较；评估载脂蛋白预测CHD的效果是否优于传统的脂质指标。设计、地点及参试者：以人群为基础的前瞻性队列来自FraminghaiR，Massachusetts。我们评估了血清总胆固醇、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、non-HDL-C、载脂蛋白（apo）A-I和apoB以及三种脂质比值（总胆固醇：HDL-C，LDL-c：HDL-C以及apoB：apoA-I）。332例中年白人参试者均参加了第4次后代检查（1987～1991年），没有心血管病。53％的参试者为女性。主要观测指标：首次CHD事件（已确诊或未确诊之心肌梗死、心绞痛、冠状动脉不全或冠心病死亡）。结果：在中位随访15年后，291例参试者（198例男性）发生CHD。在校正非脂质危险因素的多变量模型中，apoB：apoA-I比值可预测CHD（在男性每增加1个sD的风险比[hazardratio，HR]，1．39；95％可信区间[CI]，1．23～1．58。女性HR，1．40；95％,CI，1．16～1．67），但是其危险比与总胆固醇：HDL—C（男性HR，1．39；95％CI，1．22～1．58。女性HR，1．39；95％CI，1．17～1．66）、LDL—C：HDL—C（男性HR，1．35；95％CI，1．18～1．54。女性HR，1．36；95％CI，1．14～1．63）相似。在男性及女性，使用apoB：apoA—I比值的模型证实其操作特征与其他脂质相似但不优于其他脂质比值。apoB：：apoA—I比值在包含所有Framinghan危险评分因子的模型，包括总胆固醇：HDL—C（男性、P=0．12；女性P=0．58），不能预测CHR危险。 结论：在这个大型人群队列，apoB：apoA-I比值预测CHD的性能与传统的脂质比值相近，但并不优于总胆固醇：HDL-C比值。在已有总胆固醇及HDL-C测量结果的条：件下，这些数据并不支持apoB或apoA-I的临床应用。

Opposite Modulatory Effects of Crataegus aronia Aqueous Extract on Platelet Aggregation in Rats

Objectives:To reveal the mechanisms behind the dual effects of Crataegus aronia(C.aronia)aqueous extract on platelet aggregation by focusing on function,regulation,expression,and signaling of platelets P_(2)Y_(12)receptors.Methods:Adult male Wistar rats(120±10 g)were classified as control received the vehicle,C.aronia(200 mg/kg),and C.aronia(2,000 mg/kg)-treated rats.After treatments for consecutive 7 days,hematological and molecular experiments were conducted to detect alterations in platelet aggregation,thromboxane B2(THXB2)and intracellular reactive oxygen species(ROS)content;protein levels of P_(2)Y_(12),p-Akt,cyclic adenosine monophosphate(c AMP),phosphorylated vasodilator-stimulated-phosphoprotein(p-VASP),nuclear factorκB(NF-κB),P-selectin,etc.in platelets were determined by Western blot;m RNA expressions of P_(2)Y_(12)and some inflammatory markers were determined by real-time polymerase chain reaction.Results:At a concentration of 200 mg/kg,C.aronia inhibited platelet aggregation through multiple interconnected mechanisms including downregulation P_(2)Y_(12)synthesis and expression,stimulating intracellular cAMP levels and protein levels of p-VASP,inhibiting platelets THXB2 release and protein levels of P-selectin.Also,it inhibited platelets level of ROS and of NF-κB,a major signaling pathway that stimulates the expression of P_(2)Y_(12)and THXA2 synthesis.Opposite findings were seen in platelets of rats received C.aronia at a concentration of 2,000 mg/kg.Interestingly,co-administration of N-acetylcysteine prevented all hematological and molecular alterations exerted by the high dose of the extract and inhibited platelet aggregation.Conclusion:Oral administration of C.aronia at low dose inhibits platelet aggregation by reducing THXB2 release,expression of P-selectin and activating c AMP and Akt signaling through two major mechanisms including downregulation of P_(2)Y_(12)and inhibition of ROS-induced activation of NF-κB,an effect that is observed to be in the opposite direction with its high dose.