用SITSSICH风险评分预测脑梗死rt-PA静脉溶栓后症状性颅内出血风险的临床研究

目的：探索SITSSICH风险评分预测中国急性脑梗死患者rt．PA静脉溶栓（时间窗为4．5h,rt．PA剂量0．9mg／kg体重）治疗后症状性颅内出血（SICH）风险的效果,为使用SITSSICH风险评分指导溶栓治疗积累临床经验。方法：对86名进行rt-PA静脉溶栓（剂量0．9mg／kg体重）的急性脑梗死患者,进行SITSSICH风险评分,并记录总分及风险水平分层结果,按总分0、1、2、3、4、5、6、7、8、≥9分,分为10组,再按风险水平低危、平均、中危、高危分为4组,记录各组患者溶栓后有颅内出血（包括SICH）的比例,各组间进行比较。结果：SITSSICH风险评分0．5分、6分、7分、8分、≥9分各组SICH的比例分别为0．0％、8．3％、10．0％、25％和50．0％,卡方检验得x2=64．38,P〈0．001（线性趋势检验）,提示随着SITSSICH风险评分值的增加SICH的比例也在增加,存在统计学上的差异。SITSSICH风险评分风险水平低危及平均组的SICH比率为0％,中危、高危组的SICH比率分别11．5％,50％,卡方检验得xZ=-59．52,P〈0．001（线性趋势检验）,提示SITSSICH风险水平越高,SICH的比例也越高,存在统计学上的差异。另外,将SITSSICH风险评分风险水平分层和出血类型做spearman等级相关分析,得到spearman相关系数0．422,P〈0．001;说明SITSSICH风险评分风险水平分层和S1CH呈正相关。结论：对于经标准的rt—PA静脉溶栓方案（时间窗为4．5h,rt-PA剂量0．9mg／kg体重）治疗中国急性脑梗死患者,SITSSICH风险评分分值的增加与SICH风险的增加呈正相关,SITSSICH风险评分是一个能够预测rt-PA静脉溶栓后sICH风险的简单易行的实用的I临床工具。     

Overexpression of sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post‐myocardial infarction in rats

The expression of the chemorepellent Sema3a is inversely related to sympathetic innervation. We investigated whether overexpression of Sema3a in the myocardial infarction (MI) border zone could attenuate sympathetic hyper‐innervation and decrease the vulnerability to malignant ventricular tachyarrhythmia (VT) in rats. Survived MI rats were randomized to phosphate buffered saline (PBS, n = 12); mock lentivirus (MLV, n = 13) and lentivirus‐mediated overexpression of Sema3a (SLV, n = 13) groups. Sham‐operated rats served as control group (CON, n = 20). Cardiac function and electrophysiological study (PES) were performed at 1 week later. Blood and tissue samples were collected for histological analysis, epinephrine (EPI), growth‐associated factor 43 (GAP43) and tyrosine hydroxylase (TH) measurements. QTc intervals were significantly shorter in SLV group than in PBS and MLV groups (168.6 ± 7.8 vs. 178.1 ± 9.5 and 180.9 ± 8.2 ms, all P < 0.01). Inducibility of VT by PES was significantly lower in the SLV group [30.8% (4/13)] than in PBS [66.7% (8/12)] and MLV [61.5% (8/13)] groups (P < 0.05). mRNA and protein expressions of Sema3a were significantly higher and the protein expression of GAP43 and TH was significantly lower at 7 days after transduction in SLV group compared with PBS, MLV and CON groups. Myocardial EPI in the border zone was also significantly lower in SLV group than in PBS and MLV group (8.73 ± 1.30 vs. 11.94 ± 1.71 and 12.24 ± 1.54 μg/g protein, P < 0.001). Overexpression of Sema3a in MI border zone could reduce the inducibility of ventricular arrhythmias by reducing sympathetic hyper‐reinnervation after infarction.     

Detrimental effects of endogenous oestrogens on primary acute myocardial infarction among postmenopausal women

Objective

Traditionally, oestrogens were considered to be protective for the cardiovascular system for premenopausal women. Therefore, we conducted a retrospective case–control study to examine the association between endogenous oestrogens and acute myocardial infarction (AMI) risk among postmenopausal women.

Methods

A case–control study was performed among 30 primary AMI patients and 60 control subjects. Baseline characteristics data was collected and endogenous sex hormones levels were determined using chemoluminescence and radioimmunoassay methods. Conditional logistic regression models were developed with adjustment for confounders.

Results

Compared with controls, the circulating oestrone, oestradiol, androstenedione and testosterone levels were significantly higher in AMI patients (P < 0.05) while the sex hormone binding globulin (SHBG) level was lower (P < 0.05). Spearman correlation coefficients showed oestradiol was positively correlated with body mass index (BMI) and waist-to-hip ratio (WHR) in cases, but not in controls. In univariable conditional logistic regression models, oestrone, oestradiol, testosterone, WHR, BMI, diabetes and hypertension were all found to be positively associated with AMI (P < 0.05). After adjusting for these factors, oestradiol (odds ratio (OR) = 4.75; 95 % confidence interval (CI) = 1.07–21.10; P = 0.04) and WHR (OR = 6.46; 95 % CI = 1.09–38.39; P = 0.04) continued to demonstrate strong positive associations with AMI.

Conclusions

A higher level of oestradiol was potentially associated with primary AMI risk among postmenopausal women.     

New-onset atrial fibrillation and prognosis in nonagenarians after acute myocardial infarction

Background

The influence of new-onset atrial fibrillation (AF) on the long-term prognosis of nonagenarians who survive acute myocardial infarction (AMI) has not been demonstrated.

Objective

Our aim was to study the association between new-onset AF and long-term prognosis of nonagenarians who survive AMI.

Methods

From a total of 96 patients aged ≥89 years admitted during a 5-year period, 64 (67 %) were discharged alive and are the focus of this study.

Results

Mean age was 91.0 ± 2.0 years, and 39 patients (61 %) were women. During admission, 9 patients (14 %) presented new-onset AF, 51 (80 %) did not present AF, and 4 (6 %) had chronic AF. During follow-up (mean 2.3 ± 2.6 years; 6.6 ± 3.6 years in survivors), 58 patients (91 %) died, including the 9 patients with new-onset AF. Cumulative survival at 6, 12, 18, 24, and 30 months was 68.3 %, 57.2 %, 49.2 %, 47.6 %, and 31.8 %, respectively. The only two independent predictors of mortality in the multivariate analysis were age (hazard ratio [HR] 1.14; 95 % confidence interval [CI] 1.01–1.28; p = 0.04) and new-onset AF (HR 2.3; 95 % CI 1.1–4.8; p = 0.02).

Conclusion

New-onset AF is a marker of poor prognosis in nonagenarians who survive AMI.     

两种途径介入治疗急性心肌梗塞疗效分析

目的：探讨对急性心梗患者行不同途径急诊经皮冠状动脉治疗（PCi）的临床疗效及预后。方法：选取我院自2011年1月至2012年12月收治的75例sT段抬高的急性心肌梗死患者作为研究对象进行回顾性调查,对比分析经桡动脉PCI（TRA—Pet）和经股动脉PCI（TFA—PCI）两组治疗疗效及出现并发症情况,包括比较两组穿刺成功率,手术时间,术中出血及术后局部及其他并发症等方面,并作统计分析,取P〈0．05为有统计学意义。结果：两组穿刺成功率及PCI手术成功率差异无统计学意义,P〉0．05。在手术操作时间上,TFA—PCI组明显长于TRA—PCI组,差异有统计学意义,P〈0．05。TFA．PCI组局部并发症发生率为11．8％．远期并发症为2．9％。TRA-PCI组局部并发症发生率为2．4％,远期并发症为7．3％,两组差别显著,P〈0．05。结论：TRA—PCI和TFA—PCI在手术时间及术后并发症上有差异,TRA—PCI术中花时间较少,术后局部并发症要轻,值得在临床上推广,但是由于有远期并发症的危险,故术后应加强肝肾功能等的监测。     

Tobacco cigarette smoking exacerbates aortic calcification in an early stage of myocardial infarction in a female mouse model

Despite increased social awareness, marketing restraints, tobacco taxation, and available smoking cessation rehab programs, active and passive smoking remain a worldwide challenging epidemic and a key risk factor for cardiovascular diseases development. Although cardiovascular (CV) protection is more pronounced in women than in men due to estrogenic effects, tobacco cigarette smoking exposure seems to alter this protection by modulating estrogen actions via undefined mechanisms. Premenopausal cigarette smoking women are at higher risk of adverse CV effects than non-smokers. In this study, we investigated the impact of cigarette smoking on early CV injury after myocardial infarction (MI) in non-menopausal female mice. Aortic arch calcification, fibrosis, reactive oxygen species, and gene expression of inflammatory and calcification genes were exaggerated in mice exposed to cigarette smoke (CS). These findings suggest that aortic injury following MI, characterized by vascular smooth muscle cells transdifferentiation, calcification, inflammation, and collagen deposition but not cardiac dysfunction is exacerbated with CS exposure. The novel findings of this study highlight the importance of aortic injury on short and long-term prognosis in CS-exposed MI females. Linking those findings to estrogen alteration is probable and entails investigation.     

Exercise protects the heart against myocardial infarction through upregulation of miR-1192

Myocardial infarction (MI) is known as a serious global problem, which has a high mortality rate and cause severe heart damage. Mounting evidence has suggested that exercise provides direct endogenous cardiac protection against various cardiovascular diseases including MI. However, the underlying mechanism of exercise’s cardioprotective effect against MI has not been fully understood. Here, we found that a 4-wk swim training exerted protective effects against MI in C57 mice, as evidenced by increased cardiac function and decreased cardiac apoptosis. A plasma miRNA profiling assay was then performed, and 10 differentially expressed miRNAs were detected. Among them, miR-1192 was increased after exercise, and it exerted significant protective effect against hypoxia in cultured neonatal cardiomyocytes. In addition, intramyocardially injection of agomiR-1192 exerted similar cardioprotective effect as exercise, and inhibition of miR-1192 using antgomiR-1192 abolished the cardioprotective effect of exercise in MI mice, suggesting that exercise exerted cardioprotection against MI through upregulation of miR-1192. Furthermore, we found that miR-1192 exerted cardioprotective effect via targeting caspase 3 in cardiomyocytes. These findings suggested that exercise protects the heart against MI through upregulation of miR-1192, and miR-1192 is a novel exerkine in exercise-induced cardioprotection against MI.     

Calpain activation mediates microgravity-induced myocardial abnormalities in mice via p38 and ERK1/2 MAPK pathways

The human cardiovascular system has adapted to function optimally in Earth''s 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47^phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47^phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47^phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47^phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.     

Association of genetic polymorphisms in ADH and ALDH2 with risk of coronary artery disease and myocardial infarction: A meta-analysis

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for alcohol metabolism in humans. Emerging evidences have shown that functional polymorphisms in ADH and ALDH genes might play a critical role in increasing coronary artery disease (CAD) and myocardial infarction (MI) risks; however, individually published studies showed inconclusive results. The aim of this meta-analysis is to evaluate the associations between the genetic polymorphisms of ADH and ALDH genes with susceptibility to CAD and MI. A literature search was conducted on PubMed, Embase, Web of Science and Chinese BioMedical databases from inception through December 1st, 2012. Crude relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Twelve case–control studies were included with a total of 9616 subjects, including 2053 CAD patients, 1436 MI patients, and 6127 healthy controls. Meta-analysis showed that mutant genotypes (GA + AA) of the rs671 polymorphism in the ALDH2 gene were associated with increased risk of both CAD and MI (CAD: RR = 1.20, 95%CI: 1.03–1.40, P = 0.021; MI: RR = 1.32, 95%CI: 1.11–1.57, P = 0.002). However, there were no significant associations of ADH genetic polymorphisms to CAD and MI risks (CAD: RR = 0.92, 95%CI: 0.73–1.15, P = 0.445; MI: RR = 0.93, 95%CI: 0.84–1.03, P = 0.148). In conclusion, this meta-analysis provides strong evidence that ALDH2 rs671 polymorphism may be associated with increased risks of CAD and MI. However, further studies are still needed to accurately determine whether ADH genetic polymorphisms are associated with susceptibility to CAD and MI.