冠状动脉粥样硬化性心脏病患者血浆BNP、HCY、CysC水平与左心结构及功能的相关性分析

摘要 目的：摘要 目的：探讨冠状动脉粥样硬化性心脏病（CHD）患者血浆脑肽钠（BNP）、同型半胱氨酸（HCY）、胱抑素C（CysC）表达水平及与左心结构及功能的相关性。方法：选择2018年12月至2021年4月本院收治的CHD患者80例（CHD组）和同期在本院进行体检的健康者80例（对照组）为研究对象,对比CHD组与对照组、不同美国纽约心脏病学会（NYHA）心功能分级的CHD患者血浆BNP、HCY、CysC水平及左心结构和功能指标,分析血浆BNP、HCY、CysC水平与左心结构和功能指标的相关性。结果：CHD组患者血浆BNP、HCY、CysC水平及室间隔厚度（IVS）、左室舒张末期内径（LVEDd）、左室收缩末期内径（LVESd）、左室收缩末期容积（LVESv）、左室舒张末期容积（LVEDv）、左心室质量（LVM）水平高于对照组,左室射血分数（LVEF）水平低于对照组（P<0.05）;血浆BNP、HCY、CysC及IVS、LVEDd、LVESd、LVESv、LVEDv、LVM水平Ⅰ级组低于Ⅱ级组,Ⅱ级组低于Ⅲ级组,Ⅲ级组低于Ⅳ级组（P＜0.05）;LVEF水平Ⅰ级组高于Ⅱ级组,Ⅱ级组高于Ⅲ级组,Ⅲ级组高于Ⅳ级组（P＜0.05）;血浆BNP、HCY、CysC水平与IVS、LVEDd、LVESd、LVESv、LVEDv、LVM水平呈正相关,与LVEF水平呈负相关（P＜0.05）。结论：CHD患者血浆BNP、HCY、CysC水平异常升高,与左心结构及功能呈明显的相关性,BNP、HCY、CysC可能参与了CHD的病理过程。     

扩张型心肌病慢性心力衰竭患者血浆脑利钠肽水平的临床意义

目的:探究扩张型心肌病慢性心力衰竭患者血浆脑利钠肽水平的临床意义。方法:收集2012年3月至2016年3月我院收治的90例扩张型心肌病慢性心力衰竭患者,将患者按照NYHA心功能分级分为A组(II级)20例、B组(III级)38例、C组(IV级)32例。比较各组患者的血浆脑力钠肽(BNP)以及超声心动图相关指标,包括左心室射血分数(LVEF)、左心房内径(LA)、左室舒张末期内径(LVEDD)以及左室收缩末期内径(LVESD),分析血浆BNP与NYHA分级和超声心动图相关指标的相关性,以及比较血浆BNP和LVEF在慢性心力衰竭病情程度中的能力。结果:C组患者的血浆BNP浓度显著高于A组和B组(P0.05),而B组患者的血浆BNP浓度显著高于A组,比较差异具有统计学意义(P0.05)。心脏超声检测发现,C组患者的LA显著高于A组(P0.05),而LVEF、LVEDD及LVESD比较差异无统计学意义(P0.05)。血浆BNP与NYHA分级呈正相关关系,但与LVEDD、LVESD、LVEF、LA无明显相关关系(P0.05)。血浆BNP对评价心力衰竭患者病情程度呈现出较强的能力(受试者工作特征曲线下面积=0.902,P0.001)。血浆BNP=523.5 pg/mL为中重度心力衰竭患者的诊断最佳值。LVEF对评价心力衰竭患者病情程度无明显能力(受试者工作特征曲线下面积=0.392,P=0.276)。结论:血浆BNP浓度对扩张型心肌病慢性心力衰竭患者的诊断、筛查以及心功能分级具有重要的临床意义。     

血清Gal-3、NT-pro-BNP及hs-CRP水平与慢性心力衰竭超声心动图指标的相关性研究

摘要 目的：探讨血清半乳糖凝聚素-3（Gal-3）、氨基末端脑钠肽前体（NT-pro-BNP）、超敏C反应蛋白（hs-CRP）水平与慢性心力衰竭超声心动图指标的相关性。方法：选择2018年2月～2019年10月我院收治的慢性心功能衰竭患者112例作为研究组,按美国心脏病协会（NYHA）分级分为Ⅱ级组43例、Ⅲ级组39例、Ⅳ级组30例,另选择同期我院体检的健康人员60例作为对照组,比较研究组和对照组及不同心功能分级的慢性心力衰竭患者血清Gal-3、NT-pro-BNP、hs-CRP 水平和超声心动图指标,分析慢性心力衰竭患者上述指标之间的相关性。结果：研究组血清Gal-3、NT-pro-BNP、hs-CRP水平显著高于对照组,E峰与A峰比值（E/A）及左心室射血分数（LVEF）显著低于对照组（P＜0.05）。随NYHA分级增加,慢性心力衰竭患者血清Gal-3、NT-pro-BNP、hs-CRP水平逐渐升高,E/A和LVEF逐渐降低（P＜0.05）。经Pearson相关性分析显示,慢性心功能衰竭患者血清Gal-3、NT-pro-BNP、hs-CRP分别与E/A、LVEF水平呈负相关关系（P＜0.05）。结论：慢性心力衰竭患者血清Gal-3、NT-pro-BNP、hs-CRP水平异常升高,与超声心动图指标相关,检测Gal-3、NT-pro-BNP、hs-CRP有助于慢性心力衰竭的诊断和病情评估。     

心房颤动血清Lp-PLA2、BNP与疾病严重程度相关性分析

摘要 目的：分析心房颤动血清脂蛋白磷脂酶（A2Lp-PLA2）、脑钠肽（BNP）与疾病严重程度相关性分析,进而为此类疾病诊疗提供参考。方法：以本院住院诊疗的110例心血管疾病患者为主体,控制研究时间为2018年8月-2021年8月,全部患者诊疗资料均保存完整且根据有无房颤分为房颤组、无房颤组,各组均有55例。检测全部患者血清Lp-PLA2、BNP水平,同时实施超声心动图、心电图检查。结果：无房颤组血清Lp-PLA2、BNP水平显著较房颤组低,（P＜0.05）;无房颤组LVEDD、LAD水平明显高于房颤组,LVEF、E/A明显低于房颤组,（P＜0.05）;无房颤组患者中,心功能Ⅱ级、Ⅲ级、Ⅳ级患者的血清Lp-PLA2、BNP均明显低于房颤组中心功能Ⅱ级、Ⅲ级、Ⅳ级的患者,（P＜0.05）;血清Lp-PLA2与LVEDD呈负相关（r=-0.867,P＜0.05）,与LAD呈负相关（-0.609,P＜0.05）,与LVEF呈正相关（r=0.657,P＜0.05）,与E/A呈正相关（r=0.785,P＜0.05）,与心功能等级呈正相关（r=0.759,P＜0.05）;BNP与LVEDD呈负相关（r=-0.769,P＜0.05）,与LAD呈负相关（-0.701,P＜0.05）,与LVEF呈正相关（r=0.645,P＜0.05）,与E/A呈正相关（r=0.724,P＜0.05）,与心功能等级呈正相关（r=0.729,P＜0.05）。结论：血清Lp-PLA2、BNP水平与心房颤动患者疾病严重程度密切相关,血清Lp-PLA2、BNP、心脏功能指标均参与了疾病的病理生理过程,其中血清Lp-PLA2和BNP与LVEF、E/A呈正相关,与LAD、LVEDD呈负相关,故临床认为血清Lp-PLA2、BNP是预测心房颤动患者风险程度的敏感指标,通过检测该指标水平,可了解机体心功能情况,有利于早期诊断疾病及评估病情发展情况。     

血清Trx1、FGL2与急性心肌梗死后心力衰竭患者预后的关系

摘要 目的：探讨血清硫氧还蛋白1（Trx1）、纤维蛋白原样蛋白2（FGL2）与急性心肌梗死后心力衰竭患者预后的关系。方法：选择2019年10月至2020年5月我院收治的158例急性心肌梗死后心力衰竭患者作为观察组,并根据心功能Killip分级分为Ⅱ级组54例、Ⅲ级组57例、Ⅳ级组47例。另选择同期我院收治的102例急性心肌梗死患者作为对照组。入院后采用酶联免疫吸附法（ELISA）检测所有患者血清Trx1、FGL2水平;观察组患者出院后随访2年,并根据是否出现主要不良心血管事件（MACE）将患者分为预后不良组和预后良好组。采用多因素Logistic回归分析影响急性心肌梗死后心力衰竭患者预后的相关因素,采用受试者工作特征（ROC）曲线评估血清Trx1、FGL2对急性心肌梗死后心力衰竭患者预后的预测价值。结果：观察组血清FGL2水平明显高于对照组,血清Trx1水平明显低于对照组（P<0.05）;心功能Killip分级Ⅳ级组患者血清Trx1水平明显低于Ⅱ级组、Ⅲ级组（P<0.05）,血清FGL2水平明显高于Ⅱ级组、Ⅲ级组（P<0.05）。预后不良组患者血清Trx1、LVEF均明显低于预后良好组,而年龄、血清FGL2及血尿酸、血肌酐、N末端B型利钠肽原（NT-proBNP）均明显高于预后良好组（P<0.05）,两组心功能Killip分级比例比较差异有统计学意义（P<0.05）。多因素Logistic回归分析显示,年龄（较高）、心功能Killip分级为Ⅳ级、Trx1下降、FGL2升高均是影响急性心肌梗死后心力衰竭患者预后的危险因素（P<0.05）。ROC曲线结果显示,血清Trx1、FGL2预测急性心肌梗死后心力衰竭患者预后的曲线下面积分别为0.807、0.811,两者联合检测预测急性心肌梗死后心力衰竭患者预后的曲线下面积为0.889。结论：急性心肌梗死后心力衰竭患者血清中Trx1水平降低,FGL2水平升高,且血清Trx1、FGL2水平与患者心功能分级及预后密切相关,可作为评估急性心肌梗死后心力衰竭患者预后的辅助性指标。     

血清Copeptin、suPAR、SIRT1与慢性心力衰竭患者心功能及短期预后的关系研究

摘要 目的：研究血清和肽素（Copeptin）、可溶性尿激酶型纤溶酶原激活物受体（suPAR）、沉默信息调节因子2相关酶1（SIRT1）与慢性心力衰竭（CHF）患者心功能及短期预后的关系。方法：选取我院2018年2月～2020年2月收治的175例CHF患者,将其按照美国纽约心功能（NYHA）分级的差异分作Ⅱ级组56例,Ⅲ级组62例,Ⅳ级组57例。另取我院同期健康体检人员50例作为对照组。比较各组血清Copeptin、suPAR、SIRT1水平及心功能指标,并进行相关性分析。此外,对所有CHF患者进行为期1年的随访,按照预后差异分作预后不良组61例及预后良好组114例。以单因素、多因素Logistic回归分析CHF患者预后的影响因素。结果：与对照组相比,CHF患者的血清Copeptin、suPAR水平及左心室舒张末期内径（LVEDD）升高,而SIRT1水平及左心室射血分数（LVEF）降低（P＜0.05）;不同心功能等级的CHF患者间比较,随着心衰程度的加重,血清Copeptin、suPAR水平及LVEDD升高,而SIRT1水平及LVEF降低（P＜0.05）。Pearson相关性分析结果显示,CHF患者血清Copeptin、suPAR水平与LVEDD均呈正相关,而与LVEF呈负相关（P＜0.05）;血清SIRT1水平与LVEDD呈负相关,而与LVEF呈正相关（P＜0.05）。单因素分析结果显示,预后不良组年龄、LVEDD、血清Copeptin、suPAR水平均高于预后良好组,而LVEF和SIRT1水平低于预后良好组（P＜0.05）。多因素Logistic回归分析结果显示,年龄偏大、LVEDD偏高、LVEF偏低、血清Copeptin、suPAR水平过高以及血清SIRT1水平过低均是CHF患者短期预后不良的危险因素（P＜0.05）。结论：血清Copeptin、suPAR、SIRT1与CHF患者的心功能及短期预后密切相关。     

不同类型慢性心力衰竭患者临床特征及心功能危险因素、预后影响因素分析

摘要 目的：分析不同类型慢性心力衰竭患者临床特征及心功能危险因素、预后影响因素。方法：回顾性分析2020年1月-2022年1月我院收治的慢性心力衰竭患者80例，根据左室射血分数（LVEF）分为A组（n=25，LVEF<30%）、B组（n=25，LVEF 40%~50%）、C组（n=25，LVEF≥50%）三组，另根据随访1年后是否存活分为生存组（n=51）和死亡组（n=29）。比较不同组别临床相关指标，采用Pearson检验分析患者临床特征与慢性心力衰竭患者心功能、预后之间的相关性，采用多因素Logistic回归分析影响慢性心力衰竭患者心功能、预后的独立危险因素。结果：A组的心率及患有冠心病、心律失常1年以上、合并非心血管疾病人数占比、LAD、RAD、Scr、Hcy水平高于B组和C组（P<0.05）。死亡组的心率及患有冠心病、心律失常1年以上、LAD、RAD、Scr水平明显高于生存组（P<0.05）。Pearson相关性检验显示，心率、冠心病、心律失常、合并非心血管疾病、LAD、RAD、Scr、Hcy水平与慢性心力衰竭患者心功能之间呈正相关（P<0.05）；心率、冠心病、心律失常、LAD、RAD、Scr水平与慢性心力衰竭患者预后之间呈正相关（P<0.05）。多因素Logistic回归分析结果显示，心率、冠心病、心律失常、合并非心血管疾病、LAD、RAD、Scr、Hcy水平是影响慢性心力衰竭患者心功能的独立危险因素（P<0.05）；心率、冠心病、心律失常、LAD、RAD、Scr水平是影响慢性心力衰竭患者预后的独立危险因素（P<0.05）。结论：心率、冠心病、心律失常、LAD、RAD、Scr水平与慢性心力衰竭患者心功能、预后之间均呈正相关，是影响慢性心力衰竭患者心功能、预后的独立危险因素，可用来预测慢性心力衰竭的发生。     

脑钠肽和D二聚体对老年心功能不全严重程度的关系及预后的影响

目的：探讨BNP和D二聚体对老年心功能不全严重程度的关系及预后的影响。方法：以2010年1月-2012年12月来我院就诊的慢性心功能不全患者为观察对象,根据心功能不全程度分为无症状组、心功能不全II级、III级、IV级3,另取健康体检者为对照,比较各组间BNP、D二聚体水平及相关性分析。结果：各患者组BNP和D二聚体水平与对照组相比明显增加（P〈0．05）;BNP与心功能不全分级、LVEDD、LAD呈直线正相关关系（P〈0．05）,与LVEF呈直线负相关关系（P〈0．05）;D二聚体与心功能不全分级、LVEDD呈直线正相关关系（P〈0．05）,与LVEF呈呈直线负相关关系（P〈0．05）,与LAD直线关系无统计学意义（P〉0．05）;BNP水平1000pg／mL以下治疗有效率80．2％,疗效优于1000pg／mL以上者（Riditz=15．245,P=0．000）,D二聚体5μg／mL以下者治疗有效率85．4％,疗效优于5μg／mL以上者（Riditz=26．354,P=0．000）。结论：BNP和D二聚体与老年心功能不全严重程度和超声心动图指标密切相关,可以作为疾病预后预测。     

慢性心力衰竭患者外周血miR-148a表达水平与炎症因子、心功能和心室重构的关系

摘要 目的：探讨慢性心力衰竭（CHF）患者血清miR-148a表达水平与炎症因子、心功能和心室重构的关系。方法：选择2017年1月~2019年1月在我院就诊的CHF患者136例,按照美国纽约心脏病学会（NYHA）心功能分级将患者分为Ⅱ级57例、Ⅲ级43例和Ⅳ级36例。实时荧光定量PCR检测血清miR-148a的表达,血清中白细胞介素-1（IL-1）、白细胞介素6（IL-6）和肿瘤坏死因子-α（TNF-α）的含量用酶联免疫吸附试验检测,使用超声心动图检测心功能和心室重构指标,主要包括左室舒张末期内径（LVEDD）、舒张末室间隔厚度（IVSD）、舒张末左室后壁厚度（PWD）、左室质量指数（LVMI）、左室射血分数（LVEF）和左室重构指数（LVRI）,采用Pearson积矩相关系数分析血清miR-148a表达水平与血清炎症因子、超声心动图指标之间的相关性。结果：CHF患者血清miR-148a表达量随心功能分级升高而降低（P均<0.05）。炎症因子（IL-1、IL-6和TNF-α）水平和LVEDD、PWD、IVSD、LVMI随心功能分级升高而升高, LVRI和LVEF随心功能分级升高而降低（P<0.05）。血清miR-148a表达量与炎症因子、IVSD、PWD和LVMI呈负相关（P<0.05）;与LVEF和LVRI呈正相关（P<0.05）。结论：血清miR-148a表达量与CHF患者血清炎症因子水平、心功能及心室重构关系密切,提示检测血清miR-148a有助于反映CHF患者病情的严重程度。     

超声心动图参数联合血清NT-pro BNP、suPAR、PTX-3预测慢性心力衰竭患者预后的临床研究

摘要 目的：探讨超声心动图参数联合血清N末端B型脑钠肽前体（NT-pro BNP）、可溶性尿激酶型纤溶酶原激活物受体（suPAR）、正五聚体蛋白-3（PTX-3）预测慢性心力衰竭（CHF）患者预后的临床价值。方法：选取2019年1月-2021年10月联勤保障部队第909医院收治的122例CHF患者作为CHF组,同期选取50例体检健康者作为对照组。比较两组超声心动图参数和血清NT-pro BNP、suPAR、PTX-3水平。CHF患者出院后随访12个月,根据预后情况分为预后不良组和预后良好组,并比较两组超声心动图参数和血清NT-pro BNP、suPAR、PTX-3水平。受试者工作特征（ROC）曲线分析超声心动图参数联合血清NT-pro BNP、suPAR、PTX-3对CHF患者预后不良的预测价值。结果：与对照组比较,CHF组左心室舒张末期直径（LVEDD）、左心室收缩末期直径（LVESD）、NT-pro BNP、suPAR、PTX-3显著升高（P＜0.05）,左心室射血分数（LVEF）显著降低（P＜0.05）。122例CHF患者出院后随访12个月,其中预后不良患者35例、预后良好患者83例。与预后良好组比较,预后不良组LVEDD、LVESD、NT-pro BNP、suPAR、PTX-3显著升高（P＜0.05）,LVEF显著降低（P＜0.05）。ROC曲线分析结果显示,LVEDD、LVESD、LVEF联合NT-pro BNP、suPAR、PTX-3预测CHF预后不良的效能最高,显著优于各项指标单独预测。结论：超声心动图参数LVEDD、LVESD、LVEF联合血清NT-pro BNP、suPAR、PTX-3预测CHF患者预后不良的价值较高,可作为预测CHF患者预后的辅助指标。     

Myofibril assembly visualized by imaging N-RAP, alpha-actinin, and actin in living cardiomyocytes

N-RAP is a striated muscle-specific scaffolding protein that organizes α-actinin and actin into symmetrical I-Z-I structures in developing myofibrils. Here we determined the order of events during myofibril assembly through time-lapse confocal microscopy of cultured embryonic chick cardiomyocytes coexpressing fluorescently tagged N-RAP and either α-actinin or actin. During de novo myofibril assembly, N-RAP assembled in fibrillar structures within the cell, with dots of α-actinin subsequently organizing along these structures. The initial fibrillar structures were reminiscent of actin fibrils, and coassembly of N-RAP and actin into newly formed fibrils supported this. The α-actinin dots subsequently broadened to Z-lines that were wider than the underlying N-RAP fibril, and N-RAP fluorescence intensity decreased. FRAP experiments showed that most of the α-actinin dynamically exchanged during all stages of myofibril assembly. In contrast, less than 20% of the N-RAP in premyofibrils was exchanged during 10-20 min after photobleaching, but this value increased to 70% during myofibril maturation. The results show that N-RAP assembles into an actin containing scaffold before α-actinin recruitment; that the N-RAP scaffold is much more stable than the assembling structural components; that N-RAP dynamics increase as assembly progresses; and that N-RAP leaves the structure after assembly is complete.     

The anatomical components of the cardiac outflow tract of the gray bichir,Polypterus senegalus: their evolutionary significance

It has been reported that in chondrichthyans the cardiac outflow tract is composed of the myocardial conus arteriosus, while in most teleosteans it consists of the nonmyocardial bulbus arteriosus. Classical studies already indicated that a conus and a bulbus coexist in several ancient actinopterygian and teleost groups. Recent work has shown that a cardiac outflow tract consisting of a conus and a bulbus is common to both cartilaginous and bony fishes. Nonetheless and despite their position at the base of the actinopterygian phylogenetic lineage, the anatomical arrangement of the cardiac outflow tract of the Polypteriformes remained uncertain. The present study of hearts from gray bichirs was intended to fill this gap. The cardiac outflow tract of the bichir consists of two main components, namely a very long conus arteriosus, furnished with valves, and a short, intrapericardial, arterial-like bulbus arteriosus, which differs from the ventral aorta because it is covered by epicardium, shows a slightly different spatial arrangement of the histological elements and is crossed by coronary arteries. Histomorphologically, the outflow tract consists of three longitudinal regions, distal, middle and proximal, an arrangement which has been suggested to be common to all vertebrates. The distal region corresponds to the bulbus, while the conus comprises the middle and proximal regions. The present findings reinforce the notion that the bulbus arteriosus of fish has played an essential role in vertebrate heart evolution as it is the precursor of the intrapericardial trunks of the aorta and pulmonary artery of birds and mammals.     

Ventricular Dyssynchrony Patterns in Left Bundle Branch Block,With and Without Heart Failure

Background

Assessment of ventricular dyssynchrony in patients with heart failure is used for selecting candidates for cardiac resynchronization therapy (CRT). The patterns of regional distribution of dyssynchrony in a population with LBBB with and without heart failure have not been well delineated. This aspect forms the object of the study.

Methods

Tissue Doppler Imaging (TDI) data of consecutive patients with heart failure and LBBB (Group A) was compared with those with LBBB and normal LV function (Group B). All patients had standard 2D-echocardigraphic examination and TDI. Tissue velocity curves obtained by placing sample volumes in opposing basal and mid segments of septal, lateral, inferior, anterior and posterior walls were analyzed. Inter ventricular dyssynchrony (IVD) was assessed by the difference between aortic and pulmonary pre ejection intervals. LV dyssynchrony (LVD) was assessed by the difference in times to peak velocity. A delay of ≥ 40 msec was considered significant for presence of IVD and LVD.

Results

There were 103 patients in Group A and 25 in Group B. The mean QRS duration and PR intervals respectively were 146 ± 25 vs. 152±20 msec and 182± 47 vs. 165±36 msec. (p=NS) LVEF in the 2 groups were (32 ± 6 % vs. 61± 11%; p< 0.01). Prevalence of dyssynchrony in the HF group compared to Group B was 72% vs. 16%, (P< 0.01). Lateral wall dyssynchrony in the 2 groups was 37% vs. 0% (p< 0.01) while septal dyssynchrony was 16% vs. 16% (p- NS).

Conclusions

72% of heart failure patients with LBBB have documented dyssynchrony on TDI, which has a heterogeneous regional distribution. Dyssynchrony may be seen in LBBB and normal hearts but it is does not involve the lateral wall. Septal dyssynchrony in heart failure patients may not have the same significance as lateral wall delay.     

Heart rate,arterial distensibility,and optimal performance of the arterial tree

In this study we explore the ability of a previously developed model of pulsatile flow for explaining the observed reduction of arterial distensibility with heart rate. The parameters relevant for the analysis are arterial wall distensibility together with permeability and reflection coefficients of the end capillaries. A non-specific artery and the ensemble of tissues supplied by that artery were considered in the model. The blood current within that artery was equalized to the sum of all micro currents in the tissues supplied by that artery. A formula emerged that relates changes in arterial distensibility with heart rate, and also with some particular aspects of microcirculation. Then, that formula was tested with data of distensibilities of the radial and carotid arteries observed at the heart rates of 63, 90, and 110 b.p.m. The formula correctly predicted the trend of decreased distensibility with heart rate for both arteries. Moreover, due to the fact that the carotid artery supplies the brain, and because the Blood–Brain barrier is highly restrictive to colloids in the blood, for the carotid artery the formula predicted a less marked decrease in distensibility than in the case of the radial artery feeding muscle tissue, which has a greater permeability to colloids, a trend that was confirmed by data. It was found that reduction of arterial distensibility with heart rate was greater in arteries that supply end capillaries with high permeability and low reflection coefficients.     

Beta-blocker therapy in unstable severe heart failure,evidence or experience?

Currently, no evidence exists on the effects of beta-receptor blocker (BRB) treatment in patients with unstable severe heart failure. When confronted with this specific patient category, clinical experience in our centre has consistently guided us to lower the dose or stop BRB therapy. To share this experience, we present three clinical case scenarios and discuss background literature motivating our approach in these patients.     

Wnt11-R, a protein closely related to mammalian Wnt11, is required for heart morphogenesis in Xenopus

Wnt11 is a secreted protein that signals through the non-canonical planar cell polarity pathway and is a potent modulator of cell behavior and movement. In human, mouse, and chicken, there is a single Wnt11 gene, but in zebrafish and Xenopus, there are two genes related to Wnt11. The originally characterized Xenopus Wnt11 gene is expressed during early embryonic development and has a critical role in regulation of gastrulation movements. We have identified a second Xenopus Wnt11-Related gene (Wnt11-R) that is expressed after gastrulation. Sequence comparison suggests that Xenopus Wnt11-R, not Wnt11, is the ortholog of mammalian and chicken Wnt11. Xenopus Wnt11-R is expressed in neural tissue, dorsal mesenchyme derived from the dermatome region of the somites, the brachial arches, and the muscle layer of the heart, similar to the expression patterns reported for mouse and chicken Wnt11. Xenopus Wnt11-R exhibits biological properties similar to those previously described for Xenopus Wnt11, in particular the ability to activate Jun-N-terminal kinase (JNK) and to induce myocardial marker expression in ventral marginal zone (VMZ) explants. Morpholino inhibition experiments demonstrate, however, that Wnt11-R is not required for cardiac differentiation, but functions in regulation of cardiac morphogenesis. Embryos with reduced Wnt11-R activity exhibit aberrant cell-cell contacts within the myocardial wall and defects in fusion of the nascent heart tube.     

1,25(OH)2-vitamin D3 actions on cell proliferation, size, gene expression, and receptor localization, in the HL-1 cardiac myocyte

The steroid hormone 1,25(OH)₂-vitamin D₃ [1,25D] has been shown to affect the growth and proliferation of primary cultures of ventricular myocytes isolated from neonatal rat hearts. The research presented here shows that the vitamin D receptor [VDR] is present in murine cardiac myocytes (HL-1 cells), and that 1,25D affects the growth, proliferation and morphology of these cells. In addition we show that 1,25D effects expression of ANP, myotrophin, and c-myc. Furthermore, 1,25D effects expression and localization of the VDR within the cell. Murine HL-1 cardiac myocytes were grown and treated with 1,25D in culture, and growth and morphology were assessed with microscopic analysis. Cells were counted and protein levels were evaluated through Western blot analysis. Subcellular localization of the VDR was determined using immunofluorescence and confocal microscopy. 1,25D was found to decrease proliferation and alter cellular morphology of the HL-1 cells. Treatment with 1,25D increased expression of myotrophin while decreasing expression of atrial natriuretic peptide [ANP] and c-myc. 1,25D treatment also increased expression and nuclear localization of the VDR in these cardiac myocytes. Thus 1,25D is an important hormone involved in modulating and maintaining heart cell structure and function.     

Turnover rates of the canine cardiac Na,K-ATPases

Two functional isoforms (₁) and ⁺ (₃) of the Na,K-ATPase catalytic subunit coexist in canine cardiac myocytes [J. Biol. Chem. (1987) 262, 8941-8943]. The in vitro turnover rates of ATP hydrolysis have been determined in sarcolemma preparations by comparing [³H]ouabain-binding and Na,K-ATPase activity at various doses of ouabain (0.3–300 nM). The correlation between the occupancy of the ouabain-binding sites and the degree of Na,K-ATPase inhibition was not linear. The results showed that the form of low-affinity for ouabain (K_d = 300–700 nM) exhibited a lower turnover rate (88 ± 10 vs. 147 ± 15 molecules of ATP hydrolyzed per second per ouabain-binding site) than the high affinity form (K_d = 1–8 nM). Thus our results indicate this specific isoform kinetic difference could contribute to differences in the cardiac cellular function.