Neokyotorphin and kyotorphin improve cardiovascular and cerebral resuscitation after heart arrest

The effects of neokyotorphin and kyotorphin, peptides isolated from hibernates, on the rate of postresuscitational restoration and survival after a 12-min heart arrest are examined. Native peptides and peptides stabilized byd-amino acids accelerate restoration of vital functions and neurological status within several days after resuscitation. It is concluded that the use of these peptides is feasible during cardiopulmonary resuscitation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 5, pp 517–520, May, 1997     

Connective tissue growth factor and cardiac fibrosis

Cardiac fibrosis is a major pathogenic factor in a variety of cardiovascular diseases and refers to an excessive deposition of extracellular matrix components in the heart, which leads to cardiac dysfunction and eventually overt heart failure. Evidence is accumulating for a crucial role of connective tissue growth factor (CTGF) in fibrotic processes in several tissues including the heart. CTGF orchestrates the actions of important local factors evoking cardiac fibrosis. The central role of CTGF as a matricellular protein modulating the fibrotic process in cardiac remodelling makes it a possible biomarker for cardiac fibrosis and a potential candidate for therapeutic intervention to mitigate fibrosis in the heart.     

Daytime sleepiness and neural cardiac modulation in sleep-related breathing disorders

Sleep-related breathing disorders are common causes of excessive daytime sleepiness, a socially and clinically relevant problem. Mechanisms responsible for daytime sleepiness are still largely unknown. We investigated whether specific alterations in autonomic cardiac modulation during sleep, commonly associated with sleep-related breathing disorders, are related to excessive daytime sleepiness. Fifty-three patients with sleep-related breathing disorders underwent nocturnal polysomnography. Excessive daytime sleepiness was diagnosed as a Multiple Sleep Latency Test response less than or equal to 600 s. We explored the relation of excessive daytime sleepiness, objectively determined, with indices of autonomic cardiac regulation, such as baroreflex sensitivity and heart rate variability, with polysomnographic indices of the severity of sleep-related breathing disorders and with quality of sleep. Patients with excessive daytime sleepiness, when compared with patients without, had significantly lower baroreflex sensitivity and significantly higher low-to-high frequency power ratio of heart rate variability during the different stages of nocturnal sleep. By contrast, no differences were found in indices quantifying the severity of sleep-related breathing disorders or sleep quality. We demonstrated that excessive daytime sleepiness is accompanied by a deranged cardiac autonomic control at night, the latter probably reflecting autonomic arousals not detectable in the EEG. As abnormal autonomic regulation is also known to be associated with increased cardiovascular risk, a possible relation between excessive daytime sleepiness and cardiovascular events in patients with sleep-related breathing disorders deserves to be investigated in future studies.     

Evaluation of Beta-Adrenergic Influences on Cardiovascular and Metabolic Adjustments to Physical and Psychological Stress

This study was designed to examine the hypothesis that certain behavioral demands may tend to trigger sympathetic mechanisms which result in metabolically excessive cardiac output elevations. Oxygen consumption and cardiac output adjustments during a contrived reaction-time shock-avoidance task were compared to a cold pressor test in healthy young male adults. The linear cardiac output/oxygen consumption relationship generated by performance on a graded exercise task was used to assess the metabolic appropriateness of cardiac output adjustments to the reaction-time task and cold pressor. The reaction-time task was generally found to evoke metabolically excessive increases in cardiac output, while cardiac output adjustments to cold pressor were more consistent with changes in metabolic demands. However, the tasks were associated with similar heart rate responses, with a significant attenuation in stroke volume during cold pressor accounting for the differential alterations in cardiac output. This finding suggests a limited reliability for heart rate as an index of cardiac performance. The effects of propranolol, which was employed to evaluate the role of sympathetic influences, indicated that beta-adrenergic mechanisms were responsible for mediating the cardiac output response to the reaction-time task, but only partially contributed to the cold pressor response. Post-hoc analyses of individual differences in cardiovascular reactivity to the reaction-time task suggest that, for hyperreactive individuals, the coping responses evoked by this task may lead to tissue overperfusion with oxygen, thereby providing a stimulus for autoregulatory vascular reflexes which may be associated with the etiology of hypertensive disease.     

Overexpression of myeloid differentiation protein 88 in mice induces mild cardiac dysfunction,but no deficit in heart morphology

Cardiac remodeling involves changes in heart shape, size, structure, and function after injury to the myocardium. The proinflammatory adaptor protein myeloid differentiation protein 88 (MyD88) contributes to cardiac remodeling. To investigate whether excessive MyD88 levels initiate spontaneous cardiac remodeling at the whole-organism level, we generated a transgenic MyD88 mouse model with a cardiac-specific promoter. MyD88 mice (male, 20-30 g, n=∼80) were born at the expected Mendelian ratio and demonstrated similar morphology of the heart and cardiomyocytes with that of wild-type controls. Although heart weight was unaffected, cardiac contractility of MyD88 hearts was mildly reduced, as shown by echocardiographic examination, compared with wild-type controls. Moreover, the cardiac dysfunction phenotype was associated with elevation of ANF and BNP expression. Collectively, our data provide novel evidence of the critical role of balanced MyD88 signaling in maintaining physiological function in the adult heart.     

Cardiac reactivity to and recovery from acute stress: Temporal associations with implicit anxiety

Excessive cardiac responses to stressful events are a risk factor for morbidity and mortality. Adverse cardiac responses are usually attributed to conscious negative stress and emotions. Yet, cardiac responses might also be affected by emotions that are not consciously reported. Here we tested this hypothesis. Sixty participants were randomly allocated to an evaluated speaking stressor or control condition. Trait, state and implicit anxiety were assessed with the State Trait Anxiety Inventory, visual analog scales and the Implicit Association Test for assessing anxiety, with the latter two assessed before and after the stressor. Results showed that the stressor did not significantly affect implicit anxiety. Yet, participants with high implicit anxiety after the stressor had an overall enhanced heart rate and larger stressor-induced decreases in heart rate variability. These associations were independent of conscious anxiety. The implications of the results for a better understanding of excessive cardiac activity are discussed.     

不同左心室构型甲亢性心肌病模型兔血浆B型脑钠肽与心功能的关系

背景：随着甲状腺功能亢进症(简称甲亢)发病率的增加,过量的甲状腺激素对心肌的毒害作用不容忽视,而B型脑钠肽作为心衰定量标志物,对甲亢性心肌病的心功能及心肌损害程度的早期估测有着良好的应用前景。目的：探索不同左心室构型兔甲亢性心肌病血浆B型脑钠肽水平变化及其与心功能的相关性。方法：随机取20只新西兰纯种白兔,连续4周腹腔注射左旋甲状腺激素(45 μg/kg),建立甲亢动物模型。出现易怒好斗、体质量减轻、饮食量增加等典型的甲亢症状兔为成功建模的实验兔共18只。对甲亢模型兔超声测量左心室数据,然后按照Ganau等的标准将此18只甲亢模型兔分为向心性肥厚组(n=7)与离心性肥厚组(n=11)。另10只兔每天腹腔注射5 mL生理盐水作为对照组。结果与结论：向心性肥厚组和离心性肥厚组血浆B型脑钠肽水平明显高于对照组(P < 0.01),而离心性肥厚组较向心性肥厚组血浆B型脑钠肽水平明显升高(P < 0.01)。与对照组相比,向心性肥厚组及离心性肥厚组二尖瓣环平均舒张期峰值血流速度减低(P < 0.01),同时离心性肥厚组二尖瓣环平均收缩期峰值血流速度亦减低 (P < 0.01)。B型脑钠肽与舒张期峰值速度及收缩期峰值速度呈负相关(均P < 0.01)。提示不同左心室构型甲亢性心肌病兔的血浆B型脑钠肽水平可较敏感的反映心功能的变化及其心肌损害程度。中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Microcirculation of the epimyocardial layer of the rat heart: no recruitment after hypoxia.

1. In vivo microscopic studies of the microcirculation of the beating mammalian heart are accomplished by use of small needles connected to the operation table, restricting excessive movement of the cardiac surface. 2. Fluorescence microscopic techniques combined with a highly sensitive TV tape system, enable to determine microvascular diameters, intercapillary distances, as well as directions and velocities of capillary flow in the epimyocardial layer of the mammalian heart. 3. During acute hypoxia, no recruitment of previously resting capillaries could be observed. 4. The capillary flow pattern of the epimyocardial layer reveals a mixed countercurrent system.     

Fatal mitochondrial cardiomyopathy in Kearns-Sayre Syndrome

Summary The clinical and postmortem findings in a 26 year old man with Kearns-Sayre syndrome are described. In the last years of his life he suffered from cardiac arrhythmias and a congestive cardiomyopathy, dying of cardiac pump failure. The heart was enlarged, especially the left ventricle which was fibrotic and excessively dilated. Histological and fine structural investigation revealed an excessive loss of myofibrils and an increase of enlarged mitochondria with lamellar and atypically tubular cristae in widespread heart muscle cells. Mitochondrial anomalies were also observed in some cells of the conductive system. This patient thus suffered not only from a mitochondrial myopathy with ragged red fibers but also from a fatal mitochondrial cardiomyopathy. The anomalies observed in the mitochondria of the conductive system cells suggest that the well-known conductive abnormalities in patients with Kearns-Sayre syndrome might be at least partly caused by disturbed function of these mitochondria.     

Nierenfunktion bei Herzinsuffizienz

Summary Congestive cardiac failure is a syndrome in which a decrease of cardiac output triggers a series of neuro-humoral compensatory mechanisms in part involving the kidney. In this response, dysfunction of atrial volume receptors as well as disturbances of the autonomic nervous system have recently been demonstrated and are held responsible for excessive stimulation of angiotensin II, followed by adverse regulatory effects. Renal hemodynamic compensation for heart failure primarily involves constriction of efferent arterioles thereby defending glomerular filtration. In this setting, the occurrance of prerenal insufficiency is indicative of a far advanced reduction in renal blood flow. Apparent diuretic resistance in the treatment of heart failure is usually caused by iatrogenic vascular compromise or by the use of a single diuretic rather than an appropriate combination. Hyponatremia, vasopressin stimulation and elevation of plasma N-epinephrine concentration have been found to be the most reliable indicators of a poor prognosis of heart failure. Atrial natriuretic peptide is stimulated in proportion to the degree of atrial distension in heart failure, however its intrarenal effects are markedly blunted or may even be absent in this particular disease.

     

CONDITIONED HEART RATE DECELERATION UNDER DIFFERENT DIMENSIONS OF RESPIRATORY CONTROL

Both accelerative and decelerative cardiac responses have been observed in studies on human heart rate conditioning. An interpretation of the contradictory responses regarded as conditioned seems to remain equivocal. Experiments generally have used shock or loud sound as the US, so that effects of respiratory and pressor reflexes on heart rate appeared to be implicated in the conditioning process. In the present experiment, the period following a simple non-aversive signal-detection task established a heart rate deceleration as the UR. During this period, subjects of three experimental groups controlled part of their respiratory cycle for 20 seconds. Respiratory control was either sustained inhalation, sustained exhalation or maintained shallow resting cycle, while control subjects exercised no respiratory restraint. The non-aversive stimulation excluded excessive heart rate acceleration and permitted a CS to coincide with onset of relaxation in the postdecision period. Only in experimental subjects was a significant conditional deceleration of heart rate found. Conditional deceleration occurred in addition to a gradual drop in heart rate level during the experiment. When respiratory activity was not controlled, a biphasic response of heart rate was observed.     

Detecting alcohol-related problems among general hospital patients with heart disease

BACKGROUND: Certain epidemiologic studies suggest that moderate alcohol consumption decreases the risk of coronary heart disease. However, long-term excessive alcohol drinking is considered a major cause for a significant incidence of heart disease. Identifying alcohol-related problems among inpatients with cardiac disease is important. METHODS: In this study, 209 male and 137 female inpatients with cardiac disease were screened for alcohol-related problems using the CAGE questionnaire. Associations of alcohol-related problems with sociodemographic and clinical variables were also investigated. RESULTS: Fifty-seven patients (16.5%) scoring positively on the CAGE questionnaire were considered as having alcohol-related problems. Logistic regression analysis revealed that alcohol-related problems were associated with sex (p = 0.00), age (p = 0.0497), and educational level (p = 0.0524). Men less than age 50, with cardiac disease and of lower education level should be considered at high risk for abnormal drinking. The probability increases from 5.2% for the whole sample to 41.9% for the group with these specific characteristics. CONCLUSIONS: The characteristics are useful for constructing a profile of the cardiology patient who is more likely to have alcohol-related problems. Early identification and vigorous and holistic treatment of these patients is important for secondary prevention of alcohol-related problems.     

ASK1 associates with troponin T and induces troponin T phosphorylation and contractile dysfunction in cardiomyocytes

There is increasing support for the idea that excessive production of proinflammatory mediators such as tumor necrosis factor (TNF) and reactive oxygen species (ROS) contribute to the pathogenesis of cardiac dysfunction. However, the mechanisms by which cytokine/ROS production mediates cardiac dysfunction have not been established. Given that apoptosis signal-regulating kinase 1 (ASK1) is highly expressed in cardiac muscle and that ASK1 is an important mediator in the signaling pathways induced by tumor necrosis factor, interleukin-1, and ROS, we used the yeast two-hybrid system with ASK1 as bait to identify ASK1 substrates from a human heart cDNA library. The cDNA encoding the cardiac troponin T (cTnT) was isolated. ASK1 specifically interacted with cTnT, but not cTnI, in vitro and in vivo via the C-terminal ASK1 domain. ASK1 specifically phosphorylated cTnT in vitro and in vivo. Mutations in cTnT (T194/S198) at an ASK1-phosphorylation consensus sequence significantly reduced phosphorylation by ASK1. ROS-induced ASK1 activation, cTnT phosphorylation, and contractile dysfunction in cardiomyocytes showed similar kinetics. Moreover, overexpression of constitutively active ASK1 induces cTnT phosphorylation and inhibits shortening and calcium transient in adult cardiomyocytes. We conclude that ASK1 plays an important role in regulation of cardiac contractile function by phosphorylating cTnT and may participate in cytokine/ROS-induced pathogenesis of cardiomyopathy and heart failure.     

层粘连蛋白和纤维粘连蛋白在过量维生素A酸致心脏畸形中的作用:免疫组织化学研究

维生素A酸是常见的一类化学致畸因子,可引起各种心脏畸形,如主动脉骑跨、室间隔缺损等.实验采用免疫组织化学方法观察层粘连蛋白和纤维粘连蛋白在心脏正常和异常发育过程中的分布和变化规律,以探讨过量维生素A酸致心脏畸形发生的机理.结果显示:心内膜垫形成之前,心内膜细胞基底面呈层粘连蛋白和纤维粘连蛋白阳性;当内膜细胞转化为内膜垫细胞时,其基底面的层粘连蛋白和纤维粘连蛋白消失,心胶质和心肌膜中层粘连蛋白、纤维粘连蛋白免疫组化染色明显增强;心内膜垫形成并融合后,其染色又明显减弱.给孕鼠灌服过量的维生素A酸18小时后,各时间组胚胎心脏的心内膜、心胶质、心肌膜的层粘连蛋白和纤维粘连蛋白均出现了不同程度的减弱.这说明层粘连蛋白和纤维粘连蛋白是内膜垫细胞粘着和迁移的主要介导物质,维生素A酸抑制其两者的合成是引起心脏畸形的一个重要途径.     

Differential reparative phenotypes between zebrafish and medaka after cardiac injury

Results : Compared with zebrafish, the medaka heart responded differently to an injury: An excessive fibrotic response occurred in the medaka heart, and existing cardiomyocytes or cardiac progenitor cells remained dormant, resulting in no numerical difference between the uncut and injured heart with respect to the number of EdU‐incorporated cardiomyocytes. The results obtained from the analysis of the medaka raldh2‐GFP transgenic line showed a lack of raldh2 expression in the endocardium. Regarding periostin expression, the localization of medaka periostin‐b, a marker of fibrillogenesis, in the medaka heart remained at the wound site at 30 dpa; whereas zebrafish periostin‐b was no longer localized at the wound but was detected in the epicardium at that time. 相似文献   

Elevated vascular endothelial cell growth factor affects mesocardial morphogenesis and inhibits normal heart bending.

Signaling by means of vascular endothelial cell growth factor (VEGF) and its receptors (VEGFRs) is required for cardiovascular development. To examine how VEGF/VEGFR receptor signaling affects early endocardial cell behavior, embryonic quail hearts were subjected to elevated VEGF165 levels (five- to nine-somite stage). Primitive embryonic hearts microinjected with recombinant human (rh)VEGF165 exhibit several distinct malformations compared with hearts in untreated embryos: the endocardial tube is malformed with tortuous cords and folds surrounded by a diminished cardiac jelly space, and the lumens of affected hearts are conspicuously reduced. Furthermore, the embryonic heart fails to loop properly. Inhibition of bending is accompanied by an apparent failure of the dorsal mesocardium to atrophy--an event thought to be necessary for heart bending. Instead of atrophy, VEGF-treated mesocardia exhibit a marked increased in the number of resident endothelial cells. Collectively, the data suggest that the abnormally robust mesocardia in VEGF-treated hearts impede the mechanical deformation required for normal heart bending. We conclude that the excessive VEGF signaling culminates in a physical or biomechanical mechanism that acts over a wide, tissue-level, length scale to cause a severe developmental defect--failure of heart bending.     

The influence of dietary cholesterol on cardiac and hepatic beta-adrenergic receptors in egyptian sand rats

We examined the effects of dietary cholesterol on cardiac and hepatic beta-adrenergic receptor functioning. Age-matched adult desert rodents (Psammomys obesus) were randomized to either a 5% cholesterol diet (CD, n = 20), or normal rabbit chow (RC, n = 18). After a 2-month exposure to the diets, animals were sacrificed and tissue from both heart and liver were retained for radioligand bindings studies. In heart tissue, cholesterol fed animals, relative to controls, showed an increased production of adenosine 3,5￠-cyclic monophosphate (cAMP) in response to isoproterenol. Cholesterol supplementation was not associated with an increase in heart beta-adrenergic receptor number. Animals fed the 5% cholesterol diet showed significant increases in the number of beta-adrenergic receptor sites in hepatic tissue (M = 13.2 vs. 10.4 pmol/mg protein, CD and RC, respectively). The increased number of receptor sites in the liver was accompanied by a significant increase in isoproterenol-stimulated cAMP production. Results are supportive of the hypothesis that dietary cholesterol contributes to an upregulation of beta-adrenergic receptor function in cardiac, as well as hepatic tissue. These findings may be relevant to the observations of excessive stress-induced cardiovascular reactivity in persons with high cholesterol levels. Supported by Grants HL-36587 and HL-46283 from the National Heart, Lung, and Blood Institute.     

Pharmacological bases of the treatment of cardiac insufficiency

Congestive heart failure is a complex physiopathological state where both myocardial hypo-contraction and excessive peripheral vasoconstriction lead to lower cardiac output. The increase in cytosolic calcium concentration triggers the contractile processus. Digitalis inhibits the Na+/K+ ATPase enzyme and indirectly increases intracellular calcium concentration. beta 1 agonists increase the synthesis of cAMP-dependent protein kinase and hence the recruitment of new receptor-operated calcium channels which increase the calcium influx and the mobilization from its intracellular storage sites. Vascular smooth muscle contraction occurs with calcium influx into the cell resulting from various receptor activation. In congestive heart failure, activation of the sympathetic nervous system and of the renin-angiotensin system leads to neurohumoral-induced peripheral vasoconstriction. Renal effects of angiotensin II and aldosterone are responsible for sodium and water retention. alpha 1-blocking agents are drugs that block competitively the catecholamines effects on vascular receptors. Angiotensin I-converting-enzyme inhibitors block the formation of the key-element of the system: angiotensin II. Both alpha 1-blocking agents and converting-enzyme inhibitors show vasodilatator effects and acutely improve hemodynamic status of patients with congestive heart failure. Converting-enzyme inhibitors exhibit specific improvement of intrarenal hemodynamics and do not induced sodium and water retention in longterm therapy.     

Reference guide to the stages of chick heart embryology.

Cardiac progenitors of the splanchnic mesoderm (primary and secondary heart field), cardiac neural crest, and the proepicardium are the major embryonic contributors to chick heart development. Their contribution to cardiac development occurs with precise timing and regulation during such processes as primary heart tube fusion, cardiac looping and accretion, cardiac septation, and the development of the coronary vasculature. Heart development is even more complex if one follows the development of the cardiac innervation, cardiac pacemaking and conduction system, endocardial cushions, valves, and even the importance of apoptosis for proper cardiac formation. This review is meant to provide a reference guide (Table 1) on the developmental timing according to the staging of Hamburger and Hamilton (1951) (HH) of these important topics in heart development for those individuals new to a chick heart research laboratory. Even individuals outside of the heart field, who are working on a gene that is also expressed in the heart, will gain information on what to look for during chick heart development. This reference guide provides complete and easy reference to the stages involved in heart development, as well as a global perspective of how these cardiac developmental events overlap temporally and spatially, making it a good bench top companion to the many recently written in-depth cardiac reviews of the molecular aspects of cardiac development.