异丙肾上腺素诱导慢性心衰模型不同方案的比较

目的 比较3种不同方案制备的动物模型,探索稳定、可靠且重复性好的小鼠慢性心力衰竭模型。方法 将25只雄性C57BL/6J小鼠随机分为4组：正常组(ZC组)、实验A组(MA组)、B组(MB组)和C组(MC组)。实验组采取不同制备方案连续注射ISO,其中MA组和MB组为浓度递减造模法,MA组(第1天10 mg/kg、第2天5 mg/kg、第3～30天2.5 mg/(kg·d);皮下注射30 d);MB组(第1天20 mg/kg、第2天10 mg/kg、第3～14天5 mg/(kg·d);皮下注射14 d);MC组(浓度恒定7.5 mg/(kg·d),腹腔注射28 d),构建慢性心衰动物模型。在注射结束后的第2天,计算各组小鼠存活率和成模率情况。通过心脏超声检测心功能,并用ELISA测定血清中NT-pro BNP、IL-6、TNF-α水平。结果 在第30天注射结束后,各实验组虽都能有效诱导慢性心力衰竭,但发现7.5 mg/kg浓度MC组的造模情况最稳定,更适合后续开展中医药相关的心衰研究。结论 ISO制备小鼠慢性心衰模型以恒定7.5 mg/(kg·d),连续腹腔注射28 d为最佳方案。     

两种心衰模型大鼠心功能的比较

目的　比较两种心衰模型大鼠心功能的特点。方法　用腹主动脉、下腔静脉穿刺造瘘法及冠脉结扎法建立不同的心衰模型 ,用Doppler超声心动图及心脏称重的方法比较其心功能的各项参数。结果　两组大鼠的相对心脏重量均有所增高。造瘘组射血分数有所下降 ,但心输出量、血压维持正常 ,而冠脉结扎组术后 3周射血分散、心输出量和平均动脉压均明显下降 ,等容舒张期延长。结论　腹主动脉、下腔静脉穿刺造瘘所造成的是高输出量心衰 ,而冠脉结扎法所造成的是低输出量心衰 ,其心衰程度更为严重。Doppler超声心动图为大鼠心功能的检测提供了一种简单、可靠、可随访的无创伤性检查方法。     

两种早期心衰大鼠模型的建立和心功能的比较

目的比较两种不同方法建立大鼠心衰模型心功能的特点,寻找大鼠模型早期心衰阶段。方法用冠脉结扎法及腹主动脉结扎法建立不同的心衰模型,用血流动力学及心脏称重的方法比较其心功能的各项指标。结果冠脉结扎组术后2周没有心功能的改变,2周后收缩和舒张功能均下降,4周达最低。腹主动脉结扎组术后14周没有心功能的下降,16周出现了舒张功能的衰竭。结论冠脉结扎法及腹主动脉结扎法均可以造成早期心衰,冠脉结扎法术后2周为早期心衰阶段,2周后同时出现收缩和舒张功能衰竭,腹主动脉结扎法术后14周为早期心衰阶段,14周后出现了舒张功能衰竭。     

快速心室起搏制备扩张型心肌病心力衰竭犬模型的方法学探讨

目的　应用快速心室起搏的方法制备扩张型心肌病心力衰竭犬模型 ,并对其方法学进行改进。方法　 6只成年健康杂种犬麻醉后先通过射频消融希氏束致Ⅲ度房室传导阻滞 ,再经静脉植入心内膜起搏电极 ,脉冲发射器为技术处理后的人用永久起搏器。起搏频率为 2 5 0次 min ,起搏时间持续 (2 3 6± 2 5 7)d。结果　除有相应症状、体征外 ,所有动物均成功制备为扩张型心肌病心力衰竭模型 ;B超和病理解剖检查证实有心脏扩大、心室壁变薄以及肝瘀血、肺瘀血 ;病理切片显示心肌细胞空泡变性、肝窦扩张充血、肺泡内含铁血黄素沉积。结论　改进后的快速心室起搏制备充血性心力衰竭动物模型的方法更为安全、可靠、实用。     

冠脉结扎和介入两种方法制备犬心肌梗死模型的比较

目的观察开胸结扎冠状动脉与闭胸明胶海绵栓塞法制备急性心肌梗死（AMI）动物模型的特点。方法分别经开胸结扎犬冠状动脉左前降支主干及闭胸冠脉栓塞的方法阻断冠脉血流;采用单级肢体导联和胸导联方式,在阻断前后监测心电图波形变化;造模72h后取心肌组织行病理切片染色。结果经心电图和病理验证,两种方法均可成功制备犬心梗模型,开胸冠脉结扎犬死亡率较高,而冠脉栓塞成活率高。结论相较开胸冠脉结扎法,闭胸栓塞法制备心梗模型对动物损伤小,成活率高,具推广价值。     

非线性模型参数估计的一种新方法

本文以正交试验为工具,利用序贯思想,提出了非线性模型参数估计的正交试验法。该法简单易行,便于推广,且与Gauss-Newton法的结果相当。     

琥珀酸美托洛尔与美托洛尔对慢性充血性心衰患者心功能的影响

目的：探讨琥珀酸美托洛尔缓释片与美托洛尔片对慢性心力衰竭患者的心功能的影响。方法：选取慢性充血性心衰患者182例临床患者资料,排除67例不符合入选标准病例后,按照服用美托洛尔剂型（缓释片、平片）分为两组,两组均为常规利尿剂ACEI等治疗。美托洛尔组患者服用每日服用25mg-50mg的美托洛尔治疗,均分2次服用。琥珀酸美托洛尔组每日服用23．75-95mg琥珀酸美托洛尔缓释片进行治疗。评价治疗前和治疗12个月后的相关指标,包括：一日5次的平均心率（晨起前,8时,12时,16时,夜间休息前共5次平均心率）、LVDd、EF、BUN、Crea。结果：治疗12个月后,两组患者心率均下降．琥珀酸美托洛尔组与美托洛尔组相比下降更明显（64．0±5．4VS69．5±7．6,P〈0．05）、LVDd、EF、BUN、Crea等指标在两组之间没有差别。结论：慢性充血性心衰患者应用琥珀酸美托洛尔较美托洛尔平片相比可明显降低平均心率。但对于心功能肾功能的影响。琥珀酸关托洛尔较美托洛尔平片相比无明显差异。     

舒适护理干预在老年慢性心衰护理中的观察与体会

目的:分析予以老年慢性心衰病人实施舒适护理干预后的临床效果。方法:从2012年1月到2014年3月于我院接受治疗的老年慢性心衰病人中,随机抽取66例作为研究对象。将其分成对照组及观察组,各33例。其中,对照组仅进行传统护理,而观察组则是实施舒适护理干预。对所选两组病人经护理干预后的临床效果进行回顾性分析。结果:经分析发现,观察组中病人,其在临床护理效果显著优于对照组,其组间的差异比较,具有统计学意义(P0.05)。结论:予以老年慢性心酸病人实施舒适护理干预,其不仅对病人不良情绪与睡眠存在极大改善作用,还有助于护理质量的提升。     

犬腋下小切口制作慢性心房颤动模型

目的探讨应用腋下小切口开胸术建立犬慢性心房颤动模型的可行性。方法取健康比格犬14只,随机分为实验组(7只)与对照组(7只)。应用左侧腋下小切口微创技术开胸植入起搏器,实验组犬以400次/分连续起搏8周诱导心房颤动,对照组不起搏。术后观察犬的一般情况,定期监测心电图,记录犬的肢体导联心电图变化,观察心房颤动的发生情况。结果14只犬均顺利完成实验。应用左侧腋下小切口微创技术开胸,手术时间缩短,术后并发症减少。实验组7只犬经连续起搏8周,均出现典型的心房颤动心电图改变。结论应用腋下小切口微创技术开胸制作犬慢性房颤模型是安全可行的,犬术后无手术死亡及严重并发症,恢复快。说明与常规切口开胸手术相比创伤明显减小,值得在犬慢性房颤模型建立中推广应用。     

辛伐他汀联合低分子肝素对慢性心衰心肺功能及相关指标的影响

目的:探索辛伐他汀联合低分子肝素对慢性心力衰竭(CHF)患者的D-二聚体、N-末端脑钠肽前体(NT-proBNP)、左室射血分数(LVEF)、左室舒末内径、血清反应蛋白(CRP)、血浆纤维蛋白原(FB)、血清总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)的影响。方法:选择我院自2010年4月至2014年7月间收治的患有CHF患者80例,按照随机数表法分成治疗组和对照组,各40例。两组均给予常规治疗,治疗组在常规治疗的基础上加用辛伐他汀和低分子肝素,治疗两个月。对比两组患者治疗前后D-二聚体、NT-proBNP、LVEF、左室舒末内径、CRP、FB、TC和LDL-C水平。结果:与治疗前相比,对照组患者治疗后的D-二聚体、NT-proBNP、LVEF、左室舒末内径、CRP、FB、TC和LDL-C水平均无明显改善,而治疗组患者上述各项指标均显著改善,差异均具有统计学意义(均P0.05)。结论:临床上应用辛伐他汀联合低分子肝素可以有效改善CHF患者的相关指标,对于疾病的治疗具有重要作用,值得在临床上应用及推广。     

Canine Cardiac Digitalis Receptors are Preserved in Congestive Heart Failure Induced by Rapid Ventricular Pacing

Abstract

In dogs, it has been reported that acute ischemia or severe and terminal heart failure results in a selective reduction of myocardial α₃ isoform of Na, K-ATPase activity. The aim of this study was to evaluate if a similar change in the two canine digitalis receptor isoforms occurs following 4 weeks of rapid ventricular pacing-induced heart failure without profound necrosis. Heart failure was induced in dogs by rapid ventricular pacing (240 beats × min^-1). Digitalis receptors were quantitated by [³H]-ouabain binding with isolated microsomal membranes from sham-operated (n = 3) and heart failure dogs (n = 4) and by Western blot analysis using specific α₁ and α₃ polyclonal antibodies. In kinetic studies, similar dissociation rates of 19 to 22 × 10^-4 s^-1 and 1.3 to 2.4 10^-4 s^-1 corresponding to high and low affinity sites respectively, were found in sham-operated and CHF dogs. Immunoblotting showed similar abundance of α₁ isoform in the two groups; however, levels of α₃ were increased by at least 50% in pacing-induced heart failure animals. In conclusion, heart failure selectively modulates the expression of cardiac α₃ isoform in dogs.     

快速起搏致心力衰竭猪模型的研究进展

制作心力衰竭动物模型的方法较多,而持续快速心脏起搏诱发的心衰在血流动力学、神经激素变化及病理改变等方面均与人的慢性心衰极相似,因此是一种较为理想的心衰动物模型。尤其是快速起搏诱导的猪心衰模型,更由于猪在生理功能、解剖结构上与人的相似而更具有应用价值。     

Usefulness Of Ivabradine To Treat "unexpected" Heart Failure Caused By "acute" Right Ventricular Pacing

We present the case of a patient with a heart failure episode induced by acute right ventricular pacing. After reversal of beta-blockers because of chronic obstructive pulmonary disease (COPD) exacerbation, the following sinus tachycardia caused a 2:1 atrioventricular block and consequent continuous right ventricular pacing. He was treated with the selective I(f) inhibitor ivabradine, that reduced both ventricular pacing percentage and heart rate without affecting atrioventricular conduction. Ivabradine may be a valuable option in treatment of patients with atrioventricular conduction disturbances.     

A Canine Model of Sustained Atrial Fibrillation Induced by Rapid Atrial Pacing and Phenylephrine

Atrial fibrillation is a common arrhythmia with considerable morbidity and mortality. Limitations in studying both the mechanisms and therapy of atrial fibrillation arise due to the paucity of models that yield sufficiently high-quality data, are not costly, and in which atrial fibrillation is sustained long enough to make the necessary observations. The canine model we present is based on the hypothesis that atrial fibrillation requires heterogeneity of repolarization, that distribution of vagal fibers is heterogeneous in the atria, and that atrial fibrillation will persist after reflex stimulation of vagal efferents by increased systemic arterial pressure. Dogs were anesthetized with morphine–chloralose because this combination maintains nearly intact autonomic control. Systemic arterial pressure was elevated approximately 75 mm Hg during infusion of phenylephrine (2 μg/kg · min⁻¹). The right atrium was paced for 20 min at 40 Hz. Atrial fibrillation was sustained after cessation of atrial pacing in dogs receiving phenylephrine, but terminated within seconds in normotensive animals. In conclusion, atrial fibrillation can be maintained for at least 40 min after cessation of rapid atrial pacing in dogs with phenylephrine-induced hypertension.Atrial fibrillation is a common arrhythmia that affects more than 2 million persons in the United States.¹ This condition is characterized by chaotic asynchronous activation and contraction of hundreds of regions of the atria, resulting in both absence of active atrial transport of blood and a rapid ventricular response. With chronic atrial fibrillation, patients can develop thromboembolism and stroke;²² and 15% of strokes in the United States occur in patients with atrial fibrillation.¹ Despite prodigious efforts to understand the mechanism of this condition and to prevent and remediate it, atrial fibrillation leads to enormous morbidity and mortality.³ One factor hindering studies of atrial fibrillation is the absence of a model in which fibrillation can be sustained for more than several seconds, although the arrhythmia can be sustained nearly permanently after weeks of rapid atrial pacing in animals with either heart failure or physical injury to the left atrium.⁸Rapid atrial pacing decreases the atrial effective refractory period, slows atrial conduction, and increases electrophysiologic heterogeneity.^10,11,20 Recently, phenylephrine was shown to increase the difference between left and right atrial and intraatrial refractory periods, thus creating heterogeneity of atrial refractoriness.¹⁶ We therefore postulated that rapid atrial pacing together with phenylephrine infusion would induce relatively sustained atrial fibrillation for at least 40 min in dogs—a duration likely to be sufficient for testing of agents with potential to convert atrial fibrillation. This report describes a simple canine model using rapid atrial pacing in which atrial fibrillation was sustained for at least 40 min.     

Calcium-Activated Potassium Current Modulates Ventricular Repolarization in Chronic Heart Failure

The role of I_KCa in cardiac repolarization remains controversial and varies across species. The relevance of the current as a therapeutic target is therefore undefined. We examined the cellular electrophysiologic effects of I_KCa blockade in controls, chronic heart failure (HF) and HF with sustained atrial fibrillation. We used perforated patch action potential recordings to maintain intrinsic calcium cycling. The I_KCa blocker (apamin 100 nM) was used to examine the role of the current in atrial and ventricular myocytes. A canine tachypacing induced model of HF (1 and 4 months, n = 5 per group) was used, and compared to a group of 4 month HF with 6 weeks of superimposed atrial fibrillation (n = 7). A group of age-matched canine controls were used (n = 8). Human atrial and ventricular myocytes were isolated from explanted end-stage failing hearts which were obtained from transplant recipients, and studied in parallel. Atrial myocyte action potentials were unchanged by I_KCa blockade in all of the groups studied. I_KCa blockade did not affect ventricular myocyte repolarization in controls. HF caused prolongation of ventricular myocyte action potential repolarization. I_KCa blockade caused further prolongation of ventricular repolarization in HF and also caused repolarization instability and early afterdepolarizations. SK2 and SK3 expression in the atria and SK3 in the ventricle were increased in canine heart failure. We conclude that during HF, I_KCa blockade in ventricular myocytes results in cellular arrhythmias. Furthermore, our data suggest an important role for I_KCa in the maintenance of ventricular repolarization stability during chronic heart failure. Our findings suggest that novel antiarrhythmic therapies should have safety and efficacy evaluated in both atria and ventricles.     

Left Atrial Size and Function in a Canine Model of Chronic Atrial Fibrillation and Heart Failure

Background

Our aim was to assess how atrial fibrillation (AF) induction, chronicity, and RR interval irregularity affect left atrial (LA) function and size in the setting of underlying heart failure (HF), and to determine whether AF effects can be mitigated by vagal nerve stimulation (VNS).

Methods

HF was induced by 4-weeks of rapid ventricular pacing in 24 dogs. Subsequently, AF was induced and maintained by atrial pacing at 600 bpm. Dogs were randomized into control (n = 9) and VNS (n = 15) groups. In the VNS group, atrioventricular node fat pad stimulation (310 μs, 20 Hz, 3–7 mA) was delivered continuously for 6 months. LA volume and LA strain data were calculated from bi-weekly echocardiograms.

Results

RR intervals decreased with HF in both groups (p = 0.001), and decreased further during AF in control group (p = 0.014), with a non-significant increase in the VNS group during AF. LA size increased with HF (p<0.0001), with no additional increase during AF. LA strain decreased with HF (p = 0.025) and further decreased after induction of AF (p = 0.0001). LA strain decreased less (p = 0.001) in the VNS than in the control group. Beat-by-beat analysis showed a curvilinear increase of LA strain with longer preceding RR interval, (r = 0.45, p <0.0001) with LA strain 1.1% higher (p = 0.02) in the VNS-treated animals, independent of preceding RR interval duration. The curvilinear relationship between ratio of preceding and pre-preceding RR intervals, and subsequent LA strain was weaker, (r = 0.28, p = 0.001). However, VNS-treated animals again had higher LA strain (by 2.2%, p = 0.002) independently of the ratio of preceding and pre-preceding RR intervals.

Conclusions

In the underlying presence of pacing-induced HF, AF decreased LA strain, with little impact on LA size. LA strain depends on the preceding RR interval duration.     

Morning Surge of Ventricular Arrhythmias in a New Arrhythmogenic Canine Model of Chronic Heart Failure Is Associated with Attenuation of Time-Of-Day Dependence of Heart Rate and Autonomic Adaptation,and Reduced Cardiac Chaos

Patients with chronic heart failure (CHF) exhibit a morning surge in ventricular arrhythmias, but the underlying cause remains unknown. The aim of this study was to determine if heart rate dynamics, autonomic input (assessed by heart rate variability (HRV)) and nonlinear dynamics as well as their abnormal time-of-day-dependent oscillations in a newly developed arrhythmogenic canine heart failure model are associated with a morning surge in ventricular arrhythmias. CHF was induced in dogs by aortic insufficiency & aortic constriction, and assessed by echocardiography. Holter monitoring was performed to study time-of-day-dependent variation in ventricular arrhythmias (PVCs, VT), traditional HRV measures, and nonlinear dynamics (including detrended fluctuations analysis α1 and α2 (DFAα1 & DFAα2), correlation dimension (CD), and Shannon entropy (SE)) at baseline, as well as 240 days (240d) and 720 days (720d) following CHF induction. LV fractional shortening was decreased at both 240d and 720d. Both PVCs and VT increased with CHF duration and showed a morning rise (2.5-fold & 1.8-fold increase at 6 AM-noon vs midnight-6 AM) during CHF. The morning rise in HR at baseline was significantly attenuated by 52% with development of CHF (at both 240d & 720d). Morning rise in the ratio of low frequency to high frequency (LF/HF) HRV at baseline was markedly attenuated with CHF. DFAα1, DFAα2, CD and SE all decreased with CHF by 31, 17, 34 and 7%, respectively. Time-of-day-dependent variations in LF/HF, CD, DFA α1 and SE, observed at baseline, were lost during CHF. Thus in this new arrhythmogenic canine CHF model, attenuated morning HR rise, blunted autonomic oscillation, decreased cardiac chaos and complexity of heart rate, as well as aberrant time-of-day-dependent variations in many of these parameters were associated with a morning surge of ventricular arrhythmias.     

Right Ventricular Systolic Dysfunction Is Common in Hypertensive Heart Failure: A Prospective Study in Sub-Saharan Africa

IntroductionRight ventricular (RV) systolic dysfunction is now recognized widely as a strong and independent predictor of adverse outcomes in patients with heart failure (HF). Reduction of RV systolic function more closely predicts impaired exercise tolerance and poor survival than does left ventricular (LV) systolic function. In spite of this, there is a dearth of data on RV function in hypertensive HF which is the commonest form of HF in sub-Saharan Africa. We therefore conducted a prospective cohort study of hypertensive HF patients presenting to the University of Abuja Teaching Hospital, Abuja, Nigeria over an 8 year period.MethodsEach subject had transthoracic echocardiography performed on them according to the guidelines of American Society of Echocardiography. RV systolic function was defined as a tricuspid annular plane systolic excursion (TAPSE) <15mm using M-mode echocardiography.ResultsRV systolic dysfunction was identified in 272 (44.5%) of the 611 subjects that were studied. Subjects with TAPSE less than 15mm had worse prognosis compared to those with TAPSE ≥15mm.There was a significant correlation between TAPSE and other adverse prognostic markers including left and right atrial area, LV size, LV mass, LV ejection fraction, restrictive mitral inflow and RV systolic pressure (RVSP). However, LV ejection fraction and right atrial area were the only independent determinants of RV systolic dysfunction.ConclusionsHypertensive HF is a major cause of RV systolic dysfunction even in a population with a low prevalence of coronary artery disease, and RV systolic dysfunction is associated with poor prognosis in hypertensive HF. Detailed assessment of RV function should therefore be part of the echocardiography evaluation of patients with hypertensive HF.     

致心律失常型右室心肌病引起的心力衰竭分子标志物的筛选

目的：筛选致心律失常型右室心肌病引起心力衰竭的分子标志物。方法：从本院的心脏病组织库中挑选5例病理诊断明确和各方面资料比较齐全的致心律失常型右室心肌病引起心力衰竭的心脏病标本(来源于心脏移植的受体),与年龄、性别和种族等因素相匹配的正常对照心脏组织(来源于心脏移植的供体)进行全基因组表达芯片的比较研究。提取致心律失常型右室心肌病的左心室组织RNA,同时提取正常对照心脏相应部位的RNA。应用晶芯人类全基因组寡核苷酸微阵列基因表达谱芯片(含有人类基因35,000个),筛选致心律失常型右室心肌病引起的心力衰竭基因表达谱的改变。应用实时定量荧光反转录聚合酶链式反应(real-time RT-PCR)验证致心律失常型右室心肌病引起的心力衰竭基因表达改变的真实性和准确性。 结果：应用基因表达芯片研究方法共筛选出78个差异表达基因,其中有35个基因在致心律失常型右室心肌病引起的心力衰竭中表达升高,而另有43个基因表达降低。其中变化较多的基因属于与代谢相关的基因。对其中36个差异表达基因应用real-time RT-PCR的方法进行了验证,差异表达基因的准确性在75%,并首次报告了心钠素在致心律失常型右室心肌病引起的心力衰竭中表达明显升高。结论：本研究在世界上首次应用基因表达芯片的方法,观察了致心律失常型右室心肌病引起的心力衰竭基因表达谱的改变,为致心律失常型右室心肌病引起的心力衰竭分子机制的阐明和寻找疾病特异的分子标志物,以用于鉴别诊断、判断病情和预后及指导个性化治疗奠定了基础。