ANP在大鼠高血压进展为心力衰竭中的作用

目的：探讨心房钠尿钛ANP 在高血压心力衰竭发展过程中的变化和氨氯地平保护心肌细胞的作用。方法：对大鼠行腹主动 脉结扎术，术后随机选择40 只大鼠分为氨氯地平（中、高、低剂量）组以及模型组，另外选取10 只健康雄性SD 大鼠作为假手术 组。采用ELISA 方法检测各组血清ANP 浓度变化。结果：随着心功能不全加重，ANP 水平逐渐上升。氨氯地平用药组大鼠的心功 能改善明显优于模型组，ANP 明显降低，且随着氨氯地平用药量上升，心功能不断改善，ANP显著下降，P<0.05。结论：对血清 ANP浓度进行测定能够反映出高血压大鼠模型心室功能不全及充血性心力衰竭严重程度。而氨氯地平能够影响机体的ANP 分 泌对心肌细胞起到保护作用，从而有效抑制心室重构，延缓高血压心力衰竭疾病进展。     

稳心颗粒联合普罗帕酮用于心律失常的疗效研究及对血清hs-CRP、TNF-α、IL-6与心功能的影响

目的:探讨稳心颗粒联合普罗帕酮治疗心律失常的临床疗效研究及对血清高敏C反应蛋白(hs-CRP)、肿瘤坏死因子(TNF)-α、白介素(IL)-6水平与心功能的影响。方法:选择2014年7月至2016年10月我院接诊的96例心律失常患者,通过随机数表法分为观察组(n=48)和对照组(n=48)。对照组给予普罗帕酮治疗,观察组在此基础上,联用稳心颗粒。治疗4周后,比较两组血清hs-CRP、TNF-α、IL-6水平、心功能、临床疗效以及不良反应的发生情况。结果:治疗后,观察组临床疗效总有效率明显高于对照组(P0.05);血清hs-CRP、TNF-α、IL-6水平均明显低于对照组(P0.05);观察组左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)显著低于对照组,左室射血分数(LVEF)明显高于对照组(P0.05);观察组不良反应发生率明显低于对照组(P0.05)。结论:稳心颗粒联合普罗帕酮治疗心律失常的效果显著,可有效改善患者心功能,安全性高,可能与其降低血清hs-CRP、TNF-α、IL-6表达有关。     

Non-invasive diagnosis methods of coronary disease based on wavelet denoising and sound analyzing

The heart sound is the characteristic signal of cardiovascular health status. The objective of this project is to explore the correlation between Wavelet Transform and noise performance of heart sound and the adaptability of classifying heart sound using bispectrum estimation. Since the wavelet has multi-scale and multi-resolution characteristics, in this paper, the heart sound signal with different frequency ranges is decomposed through wavelet and displayed on different scales of the resolving wavelet result. According to distribution features of frequency of heart sound signals, the interference components in heart sound signal can be eliminated by selecting reconstruction coefficients. Comparing de-noising effects of four wavelets which are haar, db6, sym8 and coif6, the db6 wavelet has achieved an optimal denoising effect to heart sound signals. The de-noising result of contrasting different layers in the db6 wavelet shows that decomposing with five layers in db6 provide the optimal performance. In practice, the db6 wavelet also shows commendable denoising effects when applying to 51 clinical heart signals. Furthermore, through the clinic analyses of 29 normal signals from healthy people and 22 abnormal heart signals from coronary heart disease patients, this method can fairly distinguish abnormal signals from normal signals by applying bispectrum estimation to denoised signals via ARMA coefficients model.     

Sustained high-pressure in the spinal subarachnoid space while arterial expansion is low may be linked to syrinx development

Syringomyelia (a spinal cord cyst) usually develops as a result of conditions that cause cerebrospinal fluid (CSF) obstruction. The mechanism of syrinx formation and enlargement remains unclear, though previous studies suggest that the fluid enters via the perivascular spaces (PVS) of the penetrating arteries of the spinal cord, and that alterations in the CSF pulse timing and pressure could contribute to enhanced PVS inflow. This study uses an idealised computational model of the PVS to investigate the factors that influence peri-arterial fluid flow. First, we used three sample patient-specific models to explore whether changes in subarachnoid space (SAS) pressures in individuals with and without syringomyelia could influence PVS inflow. Second we conducted a parametric study to determine how features of the CSF pulse altered perivascular fluid, including alterations to timing and magnitude of the peak SAS pressure, the timing of reversal from high to low pressure (diastolic phase), and the area under the pressure–time curve. The model for the patient with syringomyelia had higher net CSF inflow to the PVS than the two subjects without syringomyelia. In the parametric study, only increasing the area under the high pressure region of the SAS pulse substantially increased PVS inflow, when coupled with a temporal shift in arterial and SAS pulses. This suggests that a period of sustained high SAS pressure while arterial diameter is low may increase net CSF pumping into the PVS.     

Neural control of heartbeat during two antagonistic behaviors: whole body withdrawal and escape swimming in the Mollusk <Emphasis Type="Italic">Clione limacina</Emphasis>

Two cardioexcitatory and one cardioinhibitory neural groups have been previously identified as the central cardioregulatory system in the pteropod mollusk Clione limacina. We describe in this study one additional element of the central cardioregulatory system, which consists of a large intestinal neuron named Z-cell with a novel effect on the heart activity. Intracellular stimulation of the Z-cell induced only auricle contractions with no effect on the ventricle activity. The Z-cell processes were traced down to the heart, and vigorous branching was found in the auricle tissue. Specific patterns of activity of the Z-cell as well as intestinal heart excitatory and inhibitory neurons were studied during initiation of two behaviors-whole body withdrawal and escape swimming. It was found that initiation of both behaviors was accompanied by activation of Z-cell and intestinal heart excitor neurons. The firing rate of neurons induced by sensory stimuli was sufficient to trigger auricle contractions in the semi-intact preparations. Video analysis of heart activity revealed that auricle indeed was activated during both active and passive avoidance reactions, though the intensity and delay of the activation were different. The possible physiological role of the auricle contractions during antagonistic forms of behavior is discussed.     

交感神经阻滞对糖尿病心腔扩张顽固心衰的疗效

目的:探讨交感神经阻滞对有糖尿病、心腔扩张的顽固心衰患者心脏收缩功能和心腔大小的影响。方法:经胸3～胸4棘突间隙穿刺至硬膜外腔,留置硬膜外导管,0.5%利多卡因3～5ml每2h推注一次,持续4w,适当辅以常规治疗。测定并比较TEB治疗前及后4w射血分数(EF)、左室内径(LVED)和左房内径(LAED)等指标的变化。结果:治疗后左室射血分数(EF)由治疗前的(31.53±9.29)%升为(44.75±8.32)%(P0.05);左室内径(LVED)由治疗前的(70.59±6.25)mm缩减到(63.59±7.05)mm(P0.05);左房内径(LAED)由治疗前的(46.16±7.19)mm缩减到(39.05±7.23)mm(P0.05)。结论:心区交感神经阻滞结合常规用药对有糖尿病、心腔扩张的顽固心衰患者的心脏功能有明显改善作用,并使其扩大的心脏明显缩小。     

Identification of genes related to heart failure using global gene expression profiling of human failing myocardium

Although various management methods have been developed for heart failure, it is necessary to investigate the diagnostic or therapeutic targets of heart failure. Accordingly, we have developed different approaches for managing heart failure by using conventional microarray analyses. We analyzed gene expression profiles of myocardial samples from 12 patients with heart failure and constructed datasets of heart failure-associated genes using clinical parameters such as pulmonary artery pressure (PAP) and ejection fraction (EF). From these 12 genes, we selected four genes with high expression levels in the heart, and examined their novelty by performing a literature-based search. In addition, we included four G-protein-coupled receptor (GPCR)-encoding genes, three enzyme-encoding genes, and one ion-channel protein-encoding gene to identify a drug target for heart failure using in silico microarray database. After the in vitro functional screening using adenovirus transfections of 12 genes into rat cardiomyocytes, we generated gene-targeting mice of five candidate genes, namely, MYLK3, GPR37L1, GPR35, MMP23, and NBC1. The results revealed that systolic blood pressure differed significantly between GPR35-KO and GPR35-WT mice as well as between GPR37L1-Tg and GPR37L1-KO mice. Further, the heart weight/body weight ratio between MYLK3-Tg and MYLK3-WT mice and between GPR37L1-Tg and GPR37L1-KO mice differed significantly. Hence, microarray analysis combined with clinical parameters can be an effective method to identify novel therapeutic targets for the prevention or management of heart failure.     

The Catecholaminergic Polymorphic Ventricular Tachycardia Mutation R33Q Disrupts the N-terminal Structural Motif That Regulates Reversible Calsequestrin Polymerization

Calsequestrin undergoes dynamic polymerization with increasing calcium concentration by front-to-front dimerization and back-to-back packing, forming wire-shaped structures. A recent finding that point mutation R33Q leads to lethal catecholaminergic polymorphic ventricular tachycardia (CPVT) implies a crucial role for the N terminus. In this study, we demonstrate that this mutation resides in a highly conserved alternately charged residue cluster (DGKDR; cluster 1) in the N-terminal end of calsequestrin. We further show that this cluster configures itself as a ring system and that the dipolar arrangement within the cluster brings about a critical conformational flip of Lys³¹-Asp³² essential for dimer stabilization by formation of a H-bond network. We additionally show that Ca²⁺-induced calsequestrin aggregation is nonlinear and reversible and can regain the native conformation by Ca²⁺ chelation with EGTA. This study suggests that cluster 1 works as a molecular switch and governs the bidirectional transition between the CASQ2 monomer and dimer. We further demonstrate that mutations disrupting the alternating charge pattern of the cluster, including R33Q, impair Ca²⁺-CASQ2 interaction, leading to altered polymerization-depolymerization dynamics. This study provides new mechanistic insight into the functional effects of the R33Q mutation and its potential role in CPVT.     

Integrin-linked kinase is a central mediator in angiotensin II type 1- and chemokine receptor CXCR4 signaling in myocardial hypertrophy

Inflammation and pro-hypertrophic signaling are important for development and progression of myocardial hypertrophy (LVH) and chronic heart failure (CHF). Here we investigated the relevance of integrin-linked kinase (ILK) for chemokine receptor CXCR4- and angiotensin II type 1-triggered signaling and its regulation and role in cardiac remodeling.Using ELISA, real-time-PCR, and Western blotting, the present study demonstrates that SDF-1 and its receptor CXCR4 are up-regulated in plasma and left ventricles, respectively, in mouse models of cardiac hypertrophy (transaortic constriction, transgenic cardiac-specific overexpression of rac1) and in human CHF in association with increased cardiac ILK-expression. In isolated cardiomyocytes, ILK is activated by CXCR4-ligation and necessary for SDF-1-triggered activation of rac1, NAD(P)H oxidase, and release of reactive oxygen species. Importantly, the pro-hypertrophic peptide angiotensin II induces ILK-activation dependent on rac1 in cardiomyocytes, where ILK is necessary for angiotensin II-mediated stimulation of hypertrophy genes and protein synthesis.We conclude that in both SDF-1- and angiotensin II-triggered signaling, ILK is a central mediator of rac1-induced oxidative stress and myocardial hypertrophy.