Myocardial protective effect of octylguanidine against the damage induced by ischemia reperfusion in rat heart

This study shows that the hydrophobic cation octylguanidine protects against myocardial damage induced by ischemia-reperfusion. The protective effect of the amine was analyzed after 5 min of coronary occlusion followed by 5 min reperfusion in rat hearts. ECG tracings from rats treated with an i.v. injection of 5 mg/kg of octylguanidine showed a total absence of post-reperfusion arrhythmias, conversely to what was observed in untreated rats. The histological images showed that myocardium fibers from treated rats were in good shape and retained their striae, also there was absence of edema. Furthermore, the accumulation of ²⁰¹Tl in hearts from these rats indicated that the tissue did not suffer disruption or impairment in membrane functions. The above correlated with the fact that mitochondria isolated from the ventricular free wall from treated rats preserved their ability to synthesize ATP. We propose that the protective effect of octylguanidine might be due to its documented inhibitory action on the opening of mitochondrial non-specific pores, a mechanism which is associated in heart injury as induced by reperfusion. (Mol Cell Biochem 269: 19–26, 2005)     

Guidelines for heart transplantation

Based on the changes in the field of heart transplantation and the treatment and prognosis of patients with heart failure, these updated guidelines were composed by a committee under the supervision of both the Netherlands Society of Cardiology and the Netherlands Association for Cardiothoracic surgery (NVVC and NVT). The indication for heart transplantation is defined as: ‘End-stage heart disease not remediable by more conservative measures’. Contraindications are: irreversible pulmonary hypertension/elevated pulmonary vascular resistance; active systemic infection; active malignancy or history of malignancy with probability of recurrence; inability to comply with complex medical regimen; severe peripheral or cerebrovascular disease and irreversible dysfunction of another organ, including diseases that may limit prognosis after heart transplantation. Considering the difficulties in defining end-stage heart failure, estimating prognosis in the individual patient and the continuing evolution of available therapies, the present criteria are broadly defined. The final acceptance is done by the transplant team which has extensive knowledge of the treatment of patients with advanced heart failure on the one hand and thorough experience with heart transplantation and mechanical circulatory support on the other hand. (Neth Heart J 2008;16:79-87.)     

心外膜的发育

心外膜是覆盖在心脏外层的间皮组织。心外膜来源于脏壁中胚层的前心外膜,后者位于心管流入极附近。心外膜的部分细胞通过上皮间充质转化进入心外膜下层,随后形成血管内皮、成纤维和平滑肌细胞,最终导致冠脉系统的形成。心外膜细胞可能形成心肌细胞,并且可能是心脏驻留干细胞的来源。因此,它在心脏修复治疗中发挥巨大作用。本文回顾了该领域的最新研究进展并且提出了目前存在的问题。     

Left ventricular assist device: a functional comparison with heart transplantation

Background A growing number of patients with end-stage heart failure undergo implantation of ventricular assist devices as a bridge to heart transplantation. Objectives In this study we investigated whether functional and haemodynamic recovery after implantation is sufficient to warrant the use of them as long-term alternative to heart transplantation. Methods We compared peak VO₂ of a group of patients three months after implantation of a ventricular assist device and three months after heart transplantation. Furthermore, we analysed the degree of haemodynamic recovery, by comparing plasma levels of BNP and creatinine before and after implantation of the device. Results After implantation of a ventricular assist device, exercise capacity improved considerably; three months after implantation peak VO₂ was 20.0±4.9 ml/kg/min (52% of predicted for age and gender). After heart transplantation exercise capacity improved even further; 24.0±3.9 ml/ kg/min (62% of predicted for age and gender) (p<0.001). In the three months after implantation, BNP plasma levels decreased from 570±307 pmol/l to 31±25 pmol/l and creatinine levels decreased from 191±82 μmol/l to 82±25 μmol/l, indicating significant unloading of the ventricles and haemodynamic recovery. Conclusion With regard to functional and haemodynamic recovery, the effect of implantation of a ventricular assist device is sufficient to justify its use as an alternative to heart transplantation. (Neth Heart J 2008;16:41-6.)     

The fibroblast growth factor signaling axis controls cardiac stem cell differentiation through regulating autophagy

The fibroblast growth factor (FGF) signaling axis plays important roles in heart development. Yet, the molecular mechanism by which the FGF regulates cardiogenesis is not fully understood. Using genetically engineered mouse and in vitro cultured embryoid body (EB) models, we demonstrate that FGF signaling suppresses premature differentiation of heart progenitor cells, as well as autophagy in outflow tract (OFT) myocardiac cells. The FGF also promotes mesoderm differentiation in embryonic stem cells (ESCs) but inhibits cardiomyocyte differentiation of the mesoderm cells at later stages. Furthermore, inhibition of FGF signaling increases myocardial differentiation and autophagy in both ex vivo cultured embryos and EBs, whereas activation of autophagy promotes myocardial differentiation. Thus, a link between FGF signals preventing premature differentiation of heart progenitor cells and suppression of autophagy has been established. These findings provide the first evidence that autophagy plays a role in heart progenitor differentiation, and suggest a new venue to regulate stem/progenitor cell differentiation.     

The fibroblast growth factor signaling axis controls cardiac stem cell differentiation through regulating autophagy

The fibroblast growth factor (FGF) signaling axis plays important roles in heart development. Yet, the molecular mechanism by which the FGF regulates cardiogenesis is not fully understood. Using genetically engineered mouse and in vitro cultured embryoid body (EB) models, we demonstrate that FGF signaling suppresses premature differentiation of heart progenitor cells, as well as autophagy in outflow tract (OFT) myocardiac cells. The FGF also promotes mesoderm differentiation in embryonic stem cells (ESCs) but inhibits cardiomyocyte differentiation of the mesoderm cells at later stages. Furthermore, inhibition of FGF signaling increases myocardial differentiation and autophagy in both ex vivo cultured embryos and EBs, whereas activation of autophagy promotes myocardial differentiation. Thus, a link between FGF signals preventing premature differentiation of heart progenitor cells and suppression of autophagy has been established. These findings provide the first evidence that autophagy plays a role in heart progenitor differentiation, and suggest a new venue to regulate stem/progenitor cell differentiation.     

新型机械心脏瓣膜的研究

目前临床使用的各种机械心脏瓣膜的主要问题是血栓栓塞和与抗凝治疗有关的出血,其缺陷在于瓣膜开启时,碟片和支架将瓣膜的整个血流通道分隔成三至四个较小的血流通道。在这种受阻隔的血流通宫,形成容易诱发血栓的高剪应力区、紊流和滞流区。我们研制的两种机械心脏瓣膜在瓣膜开启时,没有任何支架和碟片分隔瓣膜的血流通道,使血流与天然心脏瓣膜中的相类似,可减少对血液的危害,从而可减少换瓣病人对抗凝治疗的依赖程度。     

Quantitative proteomic profiling identifies global protein network dynamics in murine embryonic heart development

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单细胞转录组测序技术在心脏发育、疾病以及医学中的 应用

单细胞转录组测序(Single-cell RNA sequencing,scRNA-seq)可以在单细胞水平描绘出每个细胞同一基因的表达量在不同细胞间的表达水平差异,使得在单细胞水平重新认识各种组织器官成为可能.目前对心脏的测序研究正从传统的普通转录组水平过渡到单细胞水平,对小鼠和人的心脏的测序陆续地发表出来.概述了s...     

Improved methods for automatic monitoring of contracting heart cells in culture

The present communication describes improved methods for isolating and plating beating heart cells from neonatal rats using collagenase and collagen-coated petri dishes. The amplitude and frequency of contraction are continuously and simultaneously measured under well defined conditions and during prolonged periods of time with a highly sensitive and thermostated instrument. Additions, e.g. drugs and toxic agents, are made through an accessory pump system that involves extensive dilution of the added compound with medium; aliquots of medium can be withdrawn for estimation of metabolites. The system described is reliable and relatively inexpensive and allows a more extensive use of isolated heart cells, especially in studies of heart functions where small changes in amplitude and frequency of beating during prolonged periods of time are important.     

一种袖珍式胎心音仪的设计和实现

研制出一种简单实用、安全可靠并具有广阔市场前景的袖珍式胎心音仪。该仪器利用超声多普勒原理,用超声探头从母体腹部提取胎儿心音信号,经过信号解调及低频放大、音频功率放大等处理,然后由耳机及扬声器输出胎心音。     

用心率变异功率谱研究出生后心率变慢的机理

目的 :探讨神经机制及心源性因素在出生后心率变慢中的作用。方法 :运用心率变异性的频域和时域分析方法 ,主要为功率谱分析方法 ,以不同年龄组的人和家兔为实验对象 ,对出生后心脏的自主神经调控进行初步探讨 ;并通过观察不同年龄组离体灌流兔心 (无神经体液因素影响 )自律性的变化 ,探讨心脏本身因素是否参与出生后心率变慢的调控。结果 :人和家兔迷走交感对心率的调控作用比在各年龄组之间有显著差异 ,且随年龄增长逐渐升高 ;家兔离体心脏的自主心率在各年龄组之间有显著差异 ,且随年龄增长逐渐降低。结论 :出生后心率减慢与神经机制有关 ,也有心脏本身因素的参与     

An Examination of the Relationship Between Resting Heart Rate Variability and Heart Rate Reactivity to a Mental Arithmetic Stressor

Resting heart rate variability can be an index of sympathetic or parasympathetic dominance, according to the frequency of the variability studied. Sympathetic dominance of this system has been linked to increased risk of cardiovascular disease (CVD). Similarly, rapid and dramatic increases in heart rate reactivity to a stressor task have also been suggested as indicating increased risk of CVD via atherogenesis. Although both of these variables have been related to the development of cardiovascular disease, and both may be related to increased sympathetic activity or parasympathetic withdrawal, most research studies have tended to focus on either variable independently of the other. In order to investigate whether these two indices of stressor reactivity were related in relatively young and healthy subjects, resting heart rate variability data were collected from 80 volunteers for 20 minutes. In addition, heart rate reactivity data were collected during a 2-minute mental arithmetic stressor, which has been previously shown to induce significant increases in heart rate. After classifying subjects according to whether their heart rate variability data were above or below the mean for their gender, heart rate reactivity data were examined via MANOVA to detect significant differences between subject groups. Females showed significant effects, and males showed nonsignificant trends, but these two sets of data were in different directions, suggesting that gender may be a confounding factor in the relationship between heart rate reactivity and heart rate variability.     

清栓酶治疗冠心病人左心功能的评价

1988至1990年期间,我们采用SV、CO、SI、CI、HI、TPR六项心功能指标测定了清栓酶对45例冠心病治疗前后左心功能的变化,结合临床症状和心电图的观察,45例冠心病患者的心功能改善率为73.3％。因而提示我们清栓酶在纠正心肌缺血,改善左心功能,防治心力衰竭等方面具有较好的效果,为治疗冠心病提供了一个新的药物。     

冠心病患者静息心率与血小板活性相关研究

目的:探讨冠心病患者静息心率与血小板活性的相关研究。方法:选择2013年1月至2014年9月于我院住院患者474例,按静息心率快慢分为三组,心率70 bmp为第一组(Q1)150例,心率位于70~85 bmp为第二组(Q2)265例,心率85 bmp为第三组(Q3)59例,三组患者均于病情稳定时行血栓弹力图(TEG)中MA值检测,同时随访3个月,观察和比较三组患者MA值变化及预后。结果:三组患者MA值分别为61.16±7.29 mm、62.02±7.46 mm、65.32±6.56 mm,第三组患者MA值与第一组或第二组患者MA值比较差异均存在统计学意义(P0.05),通过血栓弹力图检测三组经花生四烯酸(AA)途径的血小板抑制率和经二磷酸腺苷(ADP)途径的血小板抑制率发现,静息心率高低与抗血小板药物作用疗效无相关关系(P0.05)。随访3个月,三组患者心绞痛、再住院、脑血管病及死亡的总发生率分别为28%、28.68%、40.67%。结论:冠心病患者静息心率越快,MA值越大即血小板活性越高,静息心率的高低与抗血小板药物作用疗效无关。     

Heart glycogen content and isoprenaline-induced myocardial lesions

The role of glycogen content in the heart for the development of isoprenaline-induced myocardial lesions (IML) was studied in Wistar rats and in two inbred rat strains: In IR rats (resistant to the development of IML) and in IS rats (sensitive to IML development).Glycogen content in the heart can be dramatically lowered or increased by various interventions. IML develop during the period of very low heart glycogen content (about 0.6 mg.g^–1) induced by isoprenaline administration. In animals with increased resistance to IML, either due to genetic factors or induced by isoprenaline pretreatment a high glycogen content in the heart is found (up to 7.5 mg.g^–1).The increase of resistance to IML development and increased glycogen content induced by isoprenaline pretreatment were accompanied by lower basal or ISO-, guanylylimidodiphosphate- (Gpp/NH/p) and forskolin-stimulated activities of adenylyl cyclase. On the other hand, these parameters did not differ between IR and IS rats in spite of the presence of significant differences in the resistance to the development of IML and in heart glycogen content in these two rats strains.These results suggest that genetically determined differences between two inbred rat strains in the resistance of the heart to the development of IML and in the heart glycogen content are caused by factors which are independent of the receptor-adenylyl cyclase complex and are therefore different from those involved in the increase of resistance and glycogen content due to isoprenaline pretreatment.     

Cardiac apoptosis: from organ failure to allograft rejection

Cardiac myocyte apoptosis has been extensively studied in the last few years. Increased interest in the field stems from the hope that pharmacological manipulation of apoptosis may become a valuable tool for preventing excessive cell death observed in different pathological conditions. This paper is not intended as a comprehensive overview of current research about life and death in the cardiovascular system, but rather as a concise update on new developments in areas that were highlighted in a recent series of excellent reviews. A short inventory of unsolved issues concerning the significance of cardiac myocyte loss through apoptosis in both physiological and pathological circumstances is addressed.     

Mechanism of relation among heart meridian,referred cardiac pain and heart

It has been demonstrated that an important clinical phenomenon often associated with visceral diseases is the referred pain to somatic structures, especially to the body area of homo-segmental innervation. It is interesting that the somatic foci of cardiac referred pain were often and mainly distributed along the heart meridian (HM), whereas the acupoints of HM have been applied to treat cardiac disease since ancient times. The purpose of this study was to investigate the neural relationship between the cardiac referred pain and the heart meridian. Fluorescent triple-labeling was injected into the pericardium, some acupoints of HM and lung meridian (LM, for control). The responses of the left cardiac sympathetic nerve and of the EMG in left HM and LM were electrophysiologically studied, when the electrical stimuli were applied to the acupoints of left HM and to the left cardiac sympathetic nerve. More double-labeled neurons in HM-heart, not in LM-heart, were observed in the ipsilateral dorsal root ganglia of the spinal segments C8-T3. Electric stimulation of the acupoints of left HM was able to elicit more responses of left cardiac sympathetic nerve than that of the LM-acupoints. Electric stimulation of the left cardiac sympathetic nerve resulted in stronger activities of EMG-response in the acupoints of left HM than in LM-acupoints. We conclude that double-labeling study has provided direct evidence for the existence of dichotomizing afferent fibers that supply both the pericardium and HM. Electrophysiological results show that HM is more closely related functionally to heart. These findings provide a possible morphological and physiological explanation for the referred cardiac pain and HM-heart interrelation.     

Antioxidant and oxidative stress changes in experimental cor pulmonale

Although right heart failure (RHF) contributes to 20% of all cardiovascular complications, most of the information available on RHF in general is based on the experiences with left heart failure. This study on RHF investigates changes in antioxidants and oxidative stress which are suggested to play a role in the transition from hypertrophy to failure. RHF subsequent to pulmonary hypertension was produced in rats by a single injection of monocrotaline (MCT, 60 mg/kg, i.p.). Based on hemodynamic, clinical and histopathologic observations, the animals were grouped in three functional stages at 1-, 2- and 6-week post-injection periods. In the 1-week group, RV pressure overload and hypertrophy, and a mild increase in antioxidant enzymes was seen. In the 2-week group, compensated HF, a significant increase in antioxidant enzymes, an increase in septal (IVS) wall thickness and leftward displacement of IVS without change in LV free wall were seen. In the 6-week group, lung and liver congestion, RVF and dilation, a decrease in antioxidant enzyme activities, increase in lipid peroxidation and severe bulging of the IVS into the left ventricle were seen. These changes in the hemodynamic, biochemical and histopathologic characteristics suggest that in early stages of MCT-induced pulmonary hypertension at 1 and 2 weeks, RV hypertrophy was accompanied by sustained hemodynamic function and an increase in antioxidant reserve. In the later stage at 6 weeks, clinical RHF was associated with abnormalities of the right heart systolic and diastolic function along with a decrease in antioxidant reserve. These biphasic changes in RV antioxidant enzymes, i.e. an increase during hypertrophy and a decrease in failure may suggest a role of oxidative stress in the pathogenesis of right ventricular dysfunction.     

Studies of adenosine incorporation in Langendorff rat heart and rat heart mitochondria

The acid-insoluble product isolated from well-oxygenated Langendorff rat heart after perfusion with [¹⁴C]adenosine was purified by phenol extraction and subjected to specific phosphorolysis by pure polynucleotide phosphorylase. TLC analysis of the reaction mixture showed that ADP was the only radioactive product, proving that the original substance was a polyribonucleotide. Studies of the time course of labelling and of the distribution of the acid-insoluble product between the mitochondrial and nuclear fractions showed that both are labelled even after 1 min at 25 °C, but at short times and low temperature more radioactivity is found in the mitochondria. The kinetics of adenosine incorporation resemble those expected for the labelling of hnRNA and mRNA. Isolated, respiring mitochondria incorporate adenosine and adenine nucleotides into acid insoluble form by a process dependent on oxidative phosphorylation and the adenine nucleotide translocase that is specific for adenine derivatives. The results are discussed in terms of the hypothesis that the polyribonucleotide might be a storage form of adenine nucleotides: it is concluded that the bulk of the labelled product is unlikely to play a major role in energy metabolism.