Application of sodium alginate microspheres in ischemic stroke modeling in miniature pigs

The miniature pig is an optimal animal model for studying nervous system disease because of its physiologic and pathologic features. However, the rete mirabile composed of arteries and veins at the skull base limits their application as a model of ischemic stroke by middle cerebral artery occlusion. The present study investigated the possibility of establishing an ischemic stroke model in the miniature pig by blocking the skull base retia with sodium alginate microspheres. Three Bama miniature pigs were used. Using the monitor of C-arm X-ray machine, sodium alginate microspheres (100-300 μm), a novel embolic material, were injected through the femoral artery, aortic arch, common carotid artery, ascending pharyngeal artery and the retia. Results were evaluated using carotid arteriography, MRI, behavior observation and histology. The unilateral rete mirabile was completely blocked, resulting in disturbance in blood supply to the basal ganglia, astasia of the right hind limb and salivation. MRI and hematoxylin-eosin staining showed an evident infarction focus in the basal ganglia. These findings indicate that sodium alginate microspheres are a suitable embolic material for blocking the skull base retia in miniature pigs to establish an ischemic stroke models.     

Cenani–Lenz syndrome restricted to limb and kidney anomalies associated with a novel LRP4 missense mutation

Cenani–Lenz syndrome (CLS) is a rare autosomal recessive developmental disorder of the limbs. The disorder is characterized by complete syndactyly with metacarpal fusions and/or oligodactyly sometimes accompanied by radioulnar synostosis. The clinical expression is variable and kidney agenesis/hypoplasia, craniofacial dysmorphism and teeth abnormalities are frequent features as well as lower limb involvement. CLS was recently associated with mutations in the low-density lipoprotein receptor-related protein 4 (LRP4) gene and dysregulated canonical WNT signaling. We have identified a large consanguineous Pakistani pedigree with 9 members affected by CLS. The affected individuals present with a consistent expression of the syndrome restricted to the limbs and kidneys. Symptoms from the lower limb are mild or absent and there were no radioulnar synostosis or craniofacial involvement. Genetic analysis using autozygosity mapping and sequencing revealed homozygosity for a novel missense mutation c.2858T > C (p.L953P) in the LRP4 gene. The mutation is located in a region encoding the highly conserved low-density lipoprotein receptor repeat class B domain of LRP4. Our findings add to the genotype–phenotype correlations in CLS and support kidney anomalies as a frequent associated feature.     

Efficacy of Carbon Dioxide Insufflation for Cerebral and Cardiac Protection During Open Heart Surgery: A Systematic Review and Meta‐Analysis

In spite of widespread application around the world, there has been controversy on the cerebral and cardiac protection efficacy of carbon dioxide insufflation (CDI) during open heart surgery. To make a comprehensive evaluation, we screened all relevant published randomized controlled trials to perform the first systematic review and meta‐analysis for CDI during open heart surgery. We searched PubMed, EMBASE, the Cochrane Controlled Clinical Trial register, WANFAN, CQVIP, and CNKI database for published articles. Randomized controlled trials were included when the research provided data of neurological complications postoperatively, creatinine kinase, MB isoenzyme (CK‐MB) on the first postoperative day, or all‐cause mortality. We chose a fixed‐effects model when the trials showed low heterogeneity, otherwise a random effects model was used. The quality of studies was assessed by modified Jadad scale. Four studies were included in this meta‐analysis. The overall pooled relative risk (RR) for neurological complications was 1.59, 95% confidence interval (CI) = [0.57, 4.46], and the z‐score for overall effect was 0.89 (P = 0.37). The standardized mean difference of the CK‐MB between groups was 1.15, 95% CI = [?1.27, 3.56], and the z‐score for overall effect was 0.93 (P = 0.35). The overall pooled RR for all‐cause mortality was 0.5, 95% CI = [0.16, 1.64], and the z‐score for overall effect was 1.14 (P = 0.25). There was no significant difference between groups. Because of the insufficiency of powerful evidences, the cerebral and cardiac protection efficacy of CDI during open heart surgery needs to be further verified by more high‐quality trials.     

The Protective Effect of St. Thomas Cardioplegia Enriched With Zacopride on the Isolated Rat Heart

The activation of the heart inward rectifier potassium channel (I_K1) can reduce the injury of myocardial cells by shortening the action potential duration and reducing intracellular calcium overload. Zacopride is a selective I_K1 agonist and suppresses triggered arrhythmias in rat hearts. This investigation studied the effects of St. Thomas (ST) cardioplegia enriched with Zacopride on the isolated rat heart model. Sprague‐Dawley rat hearts were harvested and perfused for 20 minutes with 37°C Krebs‐Henseleit (KH) buffer followed by 15 minute perfusion with 4°C calcium‐free KH buffer in the Control group (Con, n = 8), ST cardioplegia in the ST group (ST, n = 8) and ST cardioplegia with Zacopride in the STZ group (STZ, n = 8). After 45 minutes of arresting, all hearts were reperfused with 37°C KH buffer for 60 minutes. Hearts in the STZ group arrested faster than the Con and ST groups (9.25 ± 2.38 s vs. 72.25 ± 8.1 s, 12.75 ± 2.87 s). The recovery of the left ventricular developed pressure, ± dP/dtmax, heart rate, and coronary flow in the STZ group is significantly better than the other two groups during reperfusion. Compared with the Con and ST groups, the STZ group showed significant decreases in the maximum carciac troponin I level (P < 0.05) and the infarct size (P < 0.05). The superoxide dismutase level in the STZ group increased during the first 20 minutes of reperfusion (P < 0.05). ST cardioplegia enriched with Zacopride has beneficial effects against ischemia‐reperfusion injury in this isolated rat heart model.     

Association between genetic variants of the ADD1 and GNB3 genes and blood pressure response to the cold pressor test in a Chinese Han population: the GenSalt Study

Genetic factors influence blood pressure (BP) response to the cold pressor test (CPT), which is a phenotype related to hypertension risk. We examined the association between variants of the α-adducin (ADD1) and guanine nucleotide binding protein (G protein) β-polypeptide 3 (GNB3) genes and BP response to the CPT. A total of 1998 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity completed the CPT. The area under the curve (AUC) above the baseline BP during the CPT was used to measure the BP response. Twelve single-nucleotide polymorphisms (SNPs) of the ADD1 and GNB3 genes were selected and genotyped. Both single-marker and haplotype association analyses were conducted using linear mixed models. The rs17833172 and rs3775067 SNPs of the ADD1 gene and the rs4963516 SNP of the GNB3 gene were significantly associated with the BP response to CPT, even after adjusting for multiple testing. For the ADD1 gene, the AA genotype of SNP rs17833172 was associated with lower systolic BP (SBP) reactivity (P<0.0001) and faster BP recovery (P=0.0003). The TT genotype of rs3775067 was associated with slower SBP recovery (P=0.004). For the GNB3 gene, the C allele of SNP rs4963516 was associated with faster diastolic BP recovery (P=0.002) and smaller overall AUC (P=0.003). Haplotype analysis indicated that the CCGC haplotype of ADD1 constructed by rs1263359, rs3775067, rs4961 and rs4963 was significantly associated with the BP response to CPT. These data suggest that genetic variants of the ADD1 and GNB3 genes may have important roles in BP response to the CPT. Future studies aimed at replicating these novel findings are warranted.     

二肽基肽酶4抑制剂心血管保护作用的研究进展

二肽基肽酶4(DPP-4)抑制剂是一类新型的糖尿病治疗药物,近年来研究显示DPP-4抑制剂对心血管系统有重要的保护作用,引起广大心脏病学者的极大兴趣。DPP-4抑制剂具有抗炎、抗动脉粥样硬化、改善心肌代谢等作用,可减少心肌梗死面积,减少缺血再灌注损伤,稳定心肌缺血时电生理状态,改善心室重构,并动员干细胞至心血管损伤处,促进组织修复。现将DPP-4抑制剂心血管保护作用的研究进展做一综述。     

急性心肌梗死患者全身与局部血浆α防御素1-3水平的变化

目的评价急性ST段抬高型心肌梗死(STEMI)时全身与局部血浆α防御素1-3(DEFA1-3)水平的变化。方法入选对象均为男性,冠状动脉正常[无冠状动脉粥样硬化性心脏病(CAD)]组31例、稳定型CAD组44例、STEMI组47例。全身血样经造影导管取自主动脉根部,局部血样(STEMI组)经抽吸导管取自罪犯血管。夹心酶联免疫吸附法(ELISA)测定血浆DEFA1-3水平。结果全身血浆DEFA1-3水平STEMI组>稳定型CAD组>无CAD组(均P<0.05)。局部与全身血浆DEFA1-3水平差异无显著性(P>0.05)。DEFA1-3诊断STEMI的最佳诊断分界点为136.3μg/L,其敏感度和特异度分别为77.2%和66.7%,受试者操作特征曲线(ROC)曲线下面积(AUC)为0.717(95%CI:0.624～0.811,P=0.000)。结论 STEMI时患者全身血浆DEFA1-3水平升高,有可能作为新型炎性标志物用于急性冠状动脉综合征患者风险或预后评估。     

心脏型肌球蛋白结合蛋白C基因缺失突变导致肥厚型心肌病特点分析

目的观察肥厚型心肌病（HCM）患者心脏型肌球蛋白结合蛋白C基因（MYBPC3）缺失突变及其表型的特点。方法在100例HCM患者中对MYBPC3的所有外显子及其侧翼内含子序列进行基因扫描,聚合酶链反应（PCR）扩增目的片段,双脱氧末段终止法测序。对突变患者进行家系调查,分析其表型特点。结果在两例先证者中分别发现两个缺失突变14262_14264delAAG和14364delG,均位于外显子25。表型分析发现两例先证者均有劳力性胸闷、胸痛和晕厥史,超声心动图表现为不对称性肥厚（室间隔/左室后壁分别为2.5、3.2）,但SAM征阴性,发病年龄分别为38岁和29岁。结论缺失突变是MYBPC3基因突变的常见形式,14262_14264delAAG或14364delG突变导致的HCM表现为不对称性心肌肥厚,患者容易出现晕厥等症状,应该警惕心源性猝死的发生。