Atrial and ventricular rat coronary arteries are differently supplied by noradrenergic, cholinergic and nitrergic, but not sensory nerve fibres

The present immunohistochemical study set out to determine the extent of perivascular innervation in the rat heart, using markers for noradrenergic sympathetic fibres (tyrosine hydroxylase = TH), cholinergic parasympathetic fibres (vesicular acetylcholine transporter = VAChT), nitrergic fibres (neuronal NO synthase = nNOS), and peptidergic sensory fibres (calcitonin gene-related peptide = CGRP). For each of these antigens, the vascular innervation density was assessed separately in the atria, the basal and the apical parts of the ventricles, and was correlated to the inner vascular diameter. The four major findings are: (1) Each of these neurochemically defined populations shows an individual distribution pattern significantly different from the others with respect to correlation with vascular diameter and occurrence along atrial versus ventricular vessels. (2) Among autonomic efferent axons, nNOS-containing fibres are far less numerous than cholinergic and noradrenergic fibres. (3) Autonomic efferent axons (noradrenergic, cholinergic, nitrergic) are much more abundant around atrial than ventricular vessels, whereas perivascular CGRP-immunoreactive sensory nerve fibres are equally distributed in the various parts of the heart. (4) Noradrenergic and cholinergic axons preferentially innervate small-diameter vessels (negative linear correlation between index of innervation and vascular diameter), whereas the supply with CGRP-immunoreactive sensory nerve fibres does not change with vascular diameter. Collectively, the present study shows individual distribution patterns for each of the neurochemically defined populations of perivascular axons along the atrial and ventricular coronary arteries, indicating a highly differentiated nervous regulation of atrial versus ventricular, and large-diameter versus resistance vessels.     

Atrial natriuretic factor in sympathetic ganglia of the rat: dependence on cholinergic innervation

Atrial natriuretic factor is detectable in the peripheral autonomic ganglia of the rat by radioimmunoassay and immunohistochemistry. In the present study, surgical and neurochemical methods were used to evaluate the source of this peptide in sympathetic ganglia. Decentralization of the ganglia and/or central administration of colchicine diminished the atrial natriuretic factor content in para- and prevertebral ganglia. Axotomy did not affect levels of ganglionic atrial natriuretic factor. A messenger ribonucleic acid species hybridizing with rat atrial natriuretic factor complementary deoxyribonucleic acid was not found within the total ribonucleic acid extracted from superior cervical ganglia. These results indicate a direct dependence of ganglionic atrial natriuretic factor on cholinergic innervation.     

Spatial distribution of nerve processes and β-adrenoreceptors in the rat atrioventricular node

Atrioventricular (AV) nodal conduction time is known to be modulated by the autonomic nervous system. The presence of numerous parasympathetic and sympathetic nerve fibres in association with conduction tissue in the heart is well authenticated. In this study, confocal microscopy was used to image the distribution of antibodies directed against the general neuronal marker PGP 9.5, tyrosine hydroxylase (TH), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and β₁ and β₂-adrenoreceptors. Serial 12 μm sections of fresh frozen tissue taken from the frontal plane of the rat atrioventricular node, His bundle and bundle branches were processed for histology, acetylcholinesterase (AChE) activity and immunohistochemistry. It was found that the AV and ventricular conduction systems were more densely innervated than the atrial and ventricular myocardium as revealed by PGP 9.5 immunoreactivity. Furthermore, the transitional cell region was more densely innervated than the midnodal cell region, while spatial distribution of total innervation was uniform throughout all AV nodal regions. AChE-reactive nerve processes were found throughout the AV and ventricular conduction systems, the spatial distribution of which was nonuniform exhibiting a paucity of AChE-reactive nerve processes in the central midnodal cell region and a preponderance in the circumferential transitional cell region. TH-immunoreactivity was uniformly distributed throughout the AV and ventricular conduction systems including the central midnodal and circumferential transitional cell regions. β₁-adrenoreceptors were found throughout the AV and ventricular conduction systems with a preponderance in the circumferential transitional cell region. β₂-adrenoreceptors were localised predominantly in AV and ventricular conduction systems with a paucity of expression in the circumferential transitional cell region. These results demonstrate that the overall uniform distribution of total nerve processes is comprised of nonuniformly distributed subpopulations of parasympathetic and sympathetic nerve processes. The observation that the midnodal cell region exhibits a differential spatial pattern of parasympathetic and sympathetic innervation suggests multiple sites for modulation of impulse conduction within this region. Moreover, the localisation of β₂-ARs in the AV conduction system, with an absence of expression in the circumferential transitional cell layer, suggests that subtype-specific pharmacological agents may have distinct effects upon AV nodal conduction.     

海沙瑞林对慢性心力衰竭大鼠心交感神经重构的影响*

目的：探讨海沙瑞林对慢性心力衰竭（ CHF）大鼠心交感神经重构的影响。 方法： SD大鼠随机分为对照 组（ Control 组）、假手术组（ Sham组）、心力衰竭组（ HF组）和海沙瑞林干预组（ HF+Hx 组），应用冠状动脉结 扎法制作CHF大鼠模型，HF+Hx 组大鼠连续4 周尾静脉注射海沙瑞林 100 μg·kg-1·d-1，其他3 组注射等量的生 理盐水。超声心动图测量左心室功能；H-E 染色及Masson 染色观察各组大鼠心肌病理结构变化；免疫组织化学和 免疫印迹检测脑钠肽（ BNP）、神经生长因子（ NGF）、酪氨酸羟化酶（TH）和生长相关蛋白43（ GAP43）表达。 结果：海沙瑞林干预升高CHF大鼠左室射血分数，改善左心室功能，减轻HF组心肌损伤结构病理改变，降低心 肌细胞内BNP 表达，增加NGF、TH和GAP43 表达，差异均具有统计学意义。 结论：CHF大鼠存在心交感神经重构， 海沙瑞林通过改变心交感神经重构， 改善心功能和CHF的预后可能是其实现心保护的机制之一。     

Anatomic distribution of autonomic neural tissue in the developing dog heart: I. Sympathetic innervation

We used immunocytochemical localization of tyrosine hydroxylase to trace the ontogenesis and anatomic distribution of sympathetic innervation in fetal, neonatal, and mature canine hearts. Sparse tyrosine hydroxylase-positive neural tissue first appeared in the atrium, including sinoatrial and atrioventricular nodes, and the ventricular epicardium at midgestation and progressively increased in extent to reach the adult pattern by 2 months following birth. Sympathetic innervation of the atrioventricular bundle occurred relatively later, with no nerve processes in the neonate but a mature pattern by 2 months. At each developmental stage the atria contained more tyrosine hydroxylase-positive neural tissue than the ventricles. Thus, sympathetic nerve processes appear in the developing canine heart earlier than was previously recognized. The time course of sympathetic innervation as defined by this anatomic study is in accord with electrophysiologic studies indicating progressive neonatal development of sympathetic effect which achieves maturity by 2 months of age.     

Localisation and quantitation of autonomic innervation in the porcine heart I: conduction system

This study was prompted by the prospect of transgenic pigs providing donor hearts for transplantation in human recipients. Autonomic innervation is important for the control of cardiac dynamics, especially in the conduction system. Our objective was to assess the relative distribution of autonomic nerves in the pig heart, focusing initially on the conduction system but addressing also the myocardium, endocardium and epicardium (see Crick et al. 1999). Quantitative immunohistochemical and histochemical techniques were adopted. All regions of the conduction system possessed a significantly higher relative density of the total neural population immunoreactive for the general neuronal marker protein gene product 9.5 (PGP 9.5) than did the adjacent myocardium. A similar density of PGP 9.5-immunoreactive innervation was observed between the sinus node, the transitional region of the atrioventricular node, and the penetrating atrioventricular bundle. A differential pattern of PGP 9.5-immunoreactive innervation was present within the atrioventricular node and between the components of the ventricular conduction tissues, the latter being formed by an intricate network of Purkinje fibres. Numerous ganglion cell bodies were present in the peripheral regions of the sinus node, in the tissues of the atrioventricular groove, and even in the interstices of the compact atrioventricular node. Acetylcholinesterase (AChE)-containing nerves were the dominant subpopulation observed, representing 60–70% of the total pattern of innervation in the nodal tissues and penetrating atrioventricular bundle. Tyrosine hydroxylase (TH)-immunoreactive nerves were the next most abundant neural subpopulation, representing 37% of the total pattern of innervation in the compact atrioventricular node compared with 25% in the transitional nodal region. A minor population of ganglion cell bodies within the atrioventricular nodal region displayed TH immunoreactivity. The dominant peptidergic nerve supply possessed immunoreactivity for neuropeptide Y (NPY), which displayed a similar pattern of distribution to that of TH-immunoreactive nerve fibres. Calcitonin gene-related peptide (CGRP)-immunoreactive nerves represented 8–9% of the total innervation of the nodal tissues and penetrating atrioventricular bundle, increasing to 14–19% in the bundle branches. Somatostatin-immunoreactive nerve fibres were relatively sparse (4–13% of total innervation) and were most abundant in the nodes, especially the compact atrioventricular node. The total pattern of innervation of the porcine conduction system was relatively homogeneous. A substantial proportion of nerve fibres innervating the nodal tissues could be traced to intracardiac ganglia indicative of an extensive intrinsic supply. The innervation of the atrioventricular node and ventricular conduction tissues was similar to that observed in the bovine heart, but markedly different to that of the human heart. It is important that we are aware of these findings in view of the future use of transgenic pig hearts in human xenotransplantation.     

Distribution and morphology of sensory and autonomic fibres in the subendocardial plexus of the rat heart

Cardiac reflexes originating from sensory receptors in the heart ensure blood supply to vital tissues and organs in the face of constantly changing demands. Atrial volume receptors are mechanically sensitive vagal afferents which relay to the medulla and hypothalamus, affecting vasopressin release and renal sympathetic activity. To date, two anatomically distinct sensory endings have been identified which may subserve cardiac mechanosensation: end-nets and flower-spray endings. To map the distribution of atrial receptors in the subendocardial space, we have double-labelled rat right atrial whole mounts for neurofilament heavy chain (NFH) and synaptic vesicle protein 2 (SV2) and generated high-resolution maps of the rat subendocardial neural plexus at the cavo-atrial region. In order to elucidate the nature of these fibres, double labelling with synaptophysin (SYN) and either NFH, calcitonin gene-related peptide (CGRP), choline acetyltransferase (ChAT) or tyrosine hydroxylase (TH) was performed. The findings show that subendocardial nerve nets are denser at the superior cavo-atrial junction than the mid-atrial region. Adluminal plexuses had the finest diameters and stained positively for synaptic vesicles (SV2 and SYN), CGRP and TH. These plexuses may represent sympathetic post-ganglionic fibres and/or sensory afferents. The latter are candidate substrates for type B volume receptors which are excited by stretch during atrial filling. Deeper nerve fibres appeared coarser and may be cholinergic (positive staining for ChAT). Flower-spray endings were never observed using immunohistochemistry but were delineated clearly with the intravital stain methylene blue. We suggest that differing nerve fibre structures form the basis by which atrial deformation and hence atrial filling is reflected to the brain.     

Postnatal development of the innervation and paraganglia in the porcine pulmonary arterial bed

The innervation of the pulmonary trunk and pulmonary arterial bed was studied in 17 pigs from birth to 6 months of age. After birth, the pulmonary trunk and extra- and intra-pulmonary arteries contained neurofilament and protein gene-product-immunoreactive nerve fibres in both the adventitia and media. The density of nerve fibres increased from birth to 2 months, this being most marked during the first 2 weeks of life. Most of the fibres in the media were presumed to be sympathetic in origin as they contained both neuropeptide tyrosine and tyrosine hydroxylase immunoreactivity. Fibres were associated with the vasa-vasorum and vascular smooth muscle running around the vessel, between the elastic laminae and smooth muscle cells, in the outer two-thirds of the media. Vasoactive intestinal polypeptide and calcitonin gene-related peptide-immunoreactive nerve fibres were found to be associated with the pulmonary trunk and extra-pulmonary artery, but generally not with the intra-pulmonary arteries. Tyrosine hydroxylase immunoreactivity was detected in the glomus cells at birth, but peptide immunoreactivity (enkephalin) was not demonstrated in paraganglia until 14 days of age. Adaptation to extra-uterine life is associated with rapid development changes in the innervation of the pig pulmonary trunk, extra- and intra-pulmonary arteries and in the expression of peptide immunoreactivity in both nerve fibres and glomus cells. These changes may have a role in the postnatal adaptation of the pulmonary circulation.     

酪氨酸羟化酶的研究进展

人体内重要的神经递质儿茶酚胺由酪氨酸合成而来，此过程中四种酶以不同方式参与儿茶酚胺合成。酪氨酸羟化酶是此过程第一个酶，既是限速酶，同时也起到催化的作用，其检测为阳性的部位可代表交感神经的分布。最近研究认为，心律失常发生增加的主要可能机制之一为心脏交感重构。神经纤维增多导致儿茶酚胺释放增多，交感神经活性增加，与副交感神经支配不均衡。因此，检测心律失常的患者心肌中酪氨酸羟化酶的阳性分布特征，可以证实交感重构是否可以作为心律失常的主要发生原因。     

Contribution of the cervical sympathetic ganglia to the innervation of the pharyngeal arch arteries and the heart in the chick embryo

In the chick heart, sympathetic innervation is derived from the sympathetic neural crest (trunk neural crest arising from somite level 10–20). Since the trunk neural crest gives rise to sympathetic ganglia of their corresponding level, it suggests that the sympathetic neural crest develops into cervical ganglia 4–14. We therefore tested the hypothesis that, in addition to the first thoracic ganglia, the cervical ganglia might contribute to cardiac innervation as well. Putative sympathetic nerve connections between the cervical ganglia and the heart were demonstrated using the differentiation markers tyrosine hydroxylase and HNK‐1. In addition, heterospecific transplantation (quail to chick) of the cardiac and trunk neural crest was used to study the relation between the sympathetic neural crest and the cervical ganglia. Quail cells were visualized using the quail nuclear antibody QCPN. The results by immunohistochemical study show that the superior and the middle cervical ganglia and possibly the carotid paraganglia contribute to the carotid nerve. This nerve subsequently joins the nodose ganglion of the vagal nerve via which it contributes to nerve fibers in cardiac vagal branches entering the arterial and venous pole of the heart. In addition, the carotid nerve contributes to nerve fibers connected to putative baro‐ and chemoreceptors in and near the wall of pharyngeal arch arteries suggesting a role of the superior and middle cervical ganglia and the paraganglia of the carotid plexus in sensory afferent innervation. The lower cervical ganglia 13 and 14 contribute predominantly to nerve branches entering the venous pole via the anterior cardinal veins. We did not observe a thoracic contribution. Heterospecific transplantation shows that the cervical ganglia 4–14 as well as the carotid paraganglia are derived from the sympathetic neural crest. The cardiac neural crest does not contribute to the neurons of the cervical ganglia. We conclude that the cervical ganglia contribute to cardiac innervation which explains the contribution of the sympathetic neural crest to the innervation of the chick heart. Anat Rec 255:407–419, 1999. © 1999 Wiley‐Liss, Inc.     

Contribution of the cervical sympathetic ganglia to the innervation of the pharyngeal arch arteries and the heart in the chick embryo.

In the chick heart, sympathetic innervation is derived from the sympathetic neural crest (trunk neural crest arising from somite level 10-20). Since the trunk neural crest gives rise to sympathetic ganglia of their corresponding level, it suggests that the sympathetic neural crest develops into cervical ganglia 4-14. We therefore tested the hypothesis that, in addition to the first thoracic ganglia, the cervical ganglia might contribute to cardiac innervation as well. Putative sympathetic nerve connections between the cervical ganglia and the heart were demonstrated using the differentiation markers tyrosine hydroxylase and HNK-1. In addition, heterospecific transplantation (quail to chick) of the cardiac and trunk neural crest was used to study the relation between the sympathetic neural crest and the cervical ganglia. Quail cells were visualized using the quail nuclear antibody QCPN. The results by immunohistochemical study show that the superior and the middle cervical ganglia and possibly the carotid paraganglia contribute to the carotid nerve. This nerve subsequently joins the nodose ganglion of the vagal nerve via which it contributes to nerve fibers in cardiac vagal branches entering the arterial and venous pole of the heart. In addition, the carotid nerve contributes to nerve fibers connected to putative baro- and chemoreceptors in and near the wall of pharyngeal arch arteries suggesting a role of the superior and middle cervical ganglia and the paraganglia of the carotid plexus in sensory afferent innervation. The lower cervical ganglia 13 and 14 contribute predominantly to nerve branches entering the venous pole via the anterior cardinal veins. We did not observe a thoracic contribution. Heterospecific transplantation shows that the cervical ganglia 4-14 as well as the carotid paraganglia are derived from the sympathetic neural crest. The cardiac neural crest does not contribute to the neurons of the cervical ganglia. We conclude that the cervical ganglia contribute to cardiac innervation which explains the contribution of the sympathetic neural crest to the innervation of the chick heart.     

The distribution of terminal sympathetic nerve fibers in bundle branches and false tendons of the bovine heart. An immunohistochemical and catecholamine histofluorescence study

Summary The sympathetic innervation in false tendons as a whole and the distribution of the terminal sympathetic nerve fibers in the conduction tissue in the bundle branches is unclear. Therefore, in the present study, false tendons and bundle branch regions of the bovine heart were examined using tyrosine hydroxylase (TH) immunohistochemistry and the glyoxylic acid induced catecholamine (CA) fluorescence method for demonstration of sympathetic nerve fibers. Acetylcholinesterase (AChE) histochemistry was also applied. Some of the nerve fascicles in the false tendons were found to contain large numers of sympathetic nerve fibers and such nerve fibers formed plexuses in the walls of arteries and arterioles in these structures. In both false tendons and bundle branches sympathetic nerve fibers 1) were non-homogeneously distributed in the conduction tissue, most regularly occurring in the channels of extracellular space that are present within the bundles of Purkinje fibres. and 2) showed the same pattern of distribution in relation to Purkinje fibre bundle surfaces as the AChE-positive nerve branches. The observations show that there is a substantial sympathetic innervation in false tendons. The final distribution of the nerve fibers in these structures and in the bundle branches are discussed in relation to what is known of tissue morphology and the occurrence of sympathetic nerve influences in these regions. In the present study, previous CA-fluorescence observations of a marked sympathetic innervation in bundle branch regions, in terms of the presence of sympathetic nerve fibers in nerve fascicles and vessel walls, were also corroborated by the application of TH-immunohistochemistry.     

Cardiac natriuretic peptide hormones during artificial cardiac pacemaker stimulation and left heart catheterization

Summary Brain natriuretic peptide (BNP) is synthesized and released predominantly in the ventricular myocardium whereas atrial natriuretic peptide (ANP) is produced mainly in the atria. This study evaluated whether artificial pacemaker stimulation or left heart catheterization results in specific changes in BNP and ANP plasma levels. Both BNP and ANP responded sensitively to changes in pacemaker stimulation (single-chamber pacemakers; pacing rates of 72 and 92/min) and during the left heart catheterization procedure. However, whereas higher pacing resulted in a more pronounced increase in plasma BNP levels, a stronger ANP release followed catheterization. This incongruous rise in ANP and BNP plasma concentrations points to at least partly independent mechanisms govering the release of BNP and ANP.Abbreviations ANP atrial natriuretic peptide - BNP brain natriuretic peptide     

Cardiac natriuretic peptides and continuously monitored atrial pressures during chronic rapid pacing in pigs

Changes in atrial natriuretic peptide (ANP), N-terminal proatrial natriuretic peptide and brain natriuretic peptide (BNP) were evaluated in relation to continuously monitored atrial pressures in a pacing model of heart failure. Pigs were subjected to rapid atrial pacing (225 beats min-1) for 3 weeks with adjustments of pacing frequencies if the pigs showed overt signs of cardiac decompensation. Atrial pressures were monitored by a telemetry system with the animals unsedated and freely moving. Left atrial pressure responded stronger and more rapidly to the initiation of pacing and to alterations in the rate of pacing than right atrial pressure. Plasma natriuretic peptide levels were measured by radioimmunoassay and all increased during pacing with BNP exhibiting the largest relative increase (2.9-fold increase relative to sham pigs). Multiple regression analysis with dummy variables was used to evaluate the relative changes in natriuretic peptides and atrial pressures and the strongest correlation was found between BNP and left atrial pressure with R 2=0.81. Termination of pacing resulted in rapid normalization of ANP values in spite of persistent elevations in atrial pressures. This may reflect an increased metabolism or an attenuated secretory response of ANP to atrial stretch with established heart failure. In conclusion, 3 weeks of rapid pacing induced significant increases in atrial pressures and natriuretic peptide levels. All the natriuretic peptides correlated with atrial pressures with BNP appearing as a more sensitive marker of cardiac filling pressures than ANP and N-terminal proatrial natriuretic peptide.     

Atrial ganglionated plexi stimulation may be an effective therapeutic tool for the treatment of heart failure

An autonomic imbalance, i.e., increased sympathetic tone and/or decreased parasympathetic tone is a critical characteristic of heart failure, which is associated with progressive ventricular remodeling, ventricular arrhythmia generation and disease progression. Increasing cardiac parasympathetic tone by vagus nerve stimulation has been shown to significantly improve heart failure symptoms, hemodynamics, left ventricular function and quality of life. However, cervical surgery is needed to position vagal stimulation electrode and vagus nerve stimulation may also cause some undesired side effects. Our recent studies showed that ablation of the main atrial ganglionated plexi (GP) facilitated the occurrence of ventricular arrhythmias in acute myocardial ischemic heart while low-intensity atrial GP stimulation inhibited the occurrence of ventricular arrhythmias during acute myocardial ischemia and ischemia reperfusion. Based on these results, we hypothesize that atrial GP stimulation may ameliorate autonomic dysfunction in heart failure, inhibit heart failure progression and improve heart failure prognosis.     

Selective sympathetic neural changes in hypertrophied right ventricle

Selective pressure overload of the right ventricle in guinea pigs resulted in early and sustained reductions in tyrosine hydroxylase and dopamine-beta-hydroxylase activities in the right ventricle. No changes in tyrosine hydroxylase activity were detected in stellate ganglia sinoatrial (SA) nodal region, atrioventricular (AV) nodal region, or left ventricle. Reductions in tyrosine hydroxylase activity in stressed right ventricle were similar regardless of duration of pulmonary artery constriction, extent of hypertrophy, presence or absence of hepatic congestion, and preservation or depletion of catecholamines. The changes may represent localized loss of sympathetic nerve fibers; factors involved directly in the process of pressure-overload-induced hypertrophy may be responsible. However, sympathetic nerves remaining in hypertrophied ventricle respond normally to cold-induced sympathetic activation. The reduction in tyrosine hydroxylase activity and the maintenance of norepinephrine turnover in residual innervation to hypertrophied right ventricle support the concept that sympathetic neural regulation of hypertrophied cardiac tissue is altered but not lost.     

The effects of stimulation of the left atrial receptors on sympathetic efferent nerve activity

1. Activation of left atrial receptors by distension of balloons at the pulmonary vein-atrial junctions caused an increase in the cardiac sympathetic nerve activity, a decrease in the renal sympathetic nerve activity, and no change in the lumbar and splenic sympathetic nerve activity.2. The cardiac and renal nerve responses to balloon distension were abolished by vagal blockade in the neck.3. The results provide additional evidence that the reflex increase in the heart rate following stimulation of the left atrial receptors is mediated by selective activation of cardiac sympathetic nerve fibres.4. The inhibitory effect of atrial receptor activation on the renal sympathetic nerve activity suggests that a neural factor, possibly involving renal haemodynamics, may be a component of the diuretic response to the activation of the left atrial receptors.5. The results provide further evidence for the selective nature of the pattern of reflex responses to left atrial receptor activation and show for the first time a directionally fractionated response from sympathetic efferent neurones.     

Neuropeptide Y innervation of the rodent pineal gland and cerebral blood vessels

Neuropeptide Y (NPY)-immunoreactivity has been shown to be present in sympathetic nerve fibres in the rat pineal gland and a dense network of NPY-containing nerve fibres demonstrated to innervate the rat circle of Willis. The NPY content of the major rabbit intracranial arteries was determined by radioimmunoassay and maximal levels found in the anterior cerebral arteries. After bilateral superior cervical ganglion (SCG) removal, no NPY was detectable in the rat pineal gland; however, significant NPY-immunoreactive nerve fibres remained throughout the rat vertebrobasilar arteries, and 47% of the assayable NPY was still present. Neither intraventricular 6-hydroxydopamine (6-OHDA) nor the combination of 6-OHDA treatment and SCG removal resulted in any further loss of NPY. In conclusion, the NPY innervation of the pineal gland originates exclusively from the peripheral sympathetic nervous system. In contrast the caudal portion of the rat circle of Willis contains NPY fibres which are resistant to sympathectomy.     

Nervous activity of afferent cardiac sympathetic fibres with atrial and ventricular endings

1. We recorded the electrical activity of single afferent cardiac fibres isolated from the third and fourth left thoracic sympathetic rami communicantes of anaesthetized cats. Their conduction velocities ranged from 12 to 32 m/sec.2. The endings of each fibre were localized to one cardiac chamber by mechanical probing of the opened heart performed at the end of the experiment.3. The impulse activity was spontaneous and, in fibres with atrial or ventricular endings, it was in phase with a particular atrial or ventricular event.4. This nervous activity increased during increases in pressure occurring in the chamber where the endings were located. Conversely, decreases in pressure were accompanied by decreased nervous discharge.5. In some experiments the left coronary artery was perfused at different flows and pressures. Brief decreases or increases in coronary flow and pressure decreased or increased, respectively, the discharge of fibres with atrial or ventricular endings. Fibres were excited by intracoronary injections of veratridine.6. Cessation of coronary pump flow increased the discharge of fibres with atrial or ventricular endings only when myocardial ischaemia was accompanied by signs of heart failure.7. These afferent cardiac sympathetic fibres which provide the spinal cord with continuous specific information on cardiac events are likely to contribute to the neural control of circulation.     

有氧运动抑制心梗后心力衰竭大鼠左室重塑及交感神经重塑

目的:探讨长期有氧运动对心梗后心力衰竭(心衰)大鼠模型左心室及交感神经重塑(结构重塑与功能重塑)的影响,为心衰的机制研究及康复治疗提供科学依据和有效方法。方法:健康雄性Wistar大鼠通过结扎冠状动脉前降支建立心梗后心衰模型,术后4周随机分为假手术安静组(S组)、心衰安静组(H组)和心衰运动组(HE组)。HE组进行10周跑台训练,S组和H组保持安静状态。超声心动术检测心脏结构与功能,即左室舒张期内径(LVIDd)、左室收缩期内径(LVIDs)、左室舒张期前壁厚度(LVAWDd)、左室收缩期前壁厚度(LVAWDs)、左室舒张期后壁厚度(LVPWDd)、左室收缩期后壁厚度(LVPWDs)、缩短分数(FS)和左室射血分数(LVEF);Masson染色进行心脏组织病理学观察并获得心肌胶原容积分数(CVF);高压液相色谱法检测心肌和血浆去甲肾上腺素(NE)水平;经皮下引导电极连续采集心电信号,对自主神经功能参数——心率变异性(HRV)进行频域分析,包括总功率谱(TP)、归一化低频功率谱(LFn)、归一化高频功率谱(HFn)和LF/HF比值;实时荧光定量PCR检测心肌I型胶原(Col-I)、III型胶原(Col-III)、心房钠尿因子(ANF)、α-肌球蛋白重链(α-MHC)、β-肌球蛋白重链(β-MHC)和肌质网Ca2+-ATP酶(SERCA2a)mRNA表达,Western blotting法检测心肌神经生长因子(NGF)及其受体(Trk A)和酪氨酸羟化酶(TH)蛋白表达。结果:(1)与S组比较,H组体重(BW)、LVIDd、FS、LVEF、TP、HFn、α-MHC和SERCA2a的mRNA,NGF、Trk A和TH的蛋白表达降低(P0.05);左室重量(LVW)、左室质量指数(LVMI)、LVAWDd、LVAWDs、LVPWDd、LVPWDs、CVF、血浆和心肌NE含量、LFn、LF/HF、ANF、β-MHC、Col-I和Col-III的mRNA表达升高(P0.05)。(2)与H组比较,HE组LVW、LVMI、LVIDd、FS、LVEF、TP、HFn、α-MHC和SERCA2a的mRNA,NGF、Trk A和TH的蛋白表达升高(P0.05);CVF、血浆和心肌NE含量、LFn、LF/HF、ANF、β-MHC、Col-I和Col-III的mRNA表达降低(P0.05)。结论:长期有氧运动可抑制心梗后心衰大鼠左室重塑与交感神经重塑,心功能和自主调节改善。