The training-induced changes on automatism, conduction and myocardial refractoriness are not mediated by parasympathetic postganglionic neurons activity

The purpose of this study is to test the role that parasympathetic postganglionic neurons could play on the adaptive electrophysiological changes produced by physical training on intrinsic myocardial automatism, conduction and refractoriness. Trained rabbits were submitted to a physical training protocol on treadmill during 6 weeks. The electrophysiological study was performed in an isolated heart preparation. The investigated myocardial properties were: (a) sinus automatism, (b) atrioventricular and ventriculoatrial conduction, (c) atrial, conduction system and ventricular refractoriness. The parameters to study the refractoriness were obtained by means of extrastimulus test at four different pacing cycle lengths (10% shorter than spontaneous sinus cycle length, 250, 200 and 150 ms) and (d) mean dominant frequency (DF) of the induced ventricular fibrillation (VF), using a spectral method. The electrophysiological protocol was performed before and during continuous atropine administration (1 μM), in order to block cholinergic receptors. Cholinergic receptor blockade did not modify either the increase in sinus cycle length, atrioventricular conduction and refractoriness (left ventricular and atrioventricular conduction system functional refractory periods) or the decrease of DF of VF. These findings reveal that the myocardial electrophysiological modifications produced by physical training are not mediated by intrinsic cardiac parasympathetic activity.     

Influence of sympatho-vagal balance on airway responsiveness in athletes

The increased prevalence of airway hyper-responsiveness (AHR) observed among athletes suggests that high-level training may contribute to the development of AHR. We investigated the possible influence of the sympatho-vagal balance on this phenomenon in 40 athletes and 10 sedentary controls. Each subject filled out a respiratory questionnaire, had a methacholine challenge, and measurements were made of their baseline plasma catecholamines [epinephrine (E), norepinephrine (NE) and dopamine (DA)] as a reflection of sympathetic tone, and their heart rate variability (SDNN: standard deviation of all normal-to-normal intervals) as an indicator of parasympathetic tone. The athletes had a 45% prevalence of AHR (defined as PC₂₀ < 16 mg/ml, where PC₂₀ is the concentration of methacholine inducing a 20% fall in the forced expiratory volume in 1 s, FEV₁) with a mean PC₂₀ of 21.2 mg/ml compared with 10% prevalence (mean PC₂₀: 74.4 mg/ml) in sedentary subjects (P < 0.01). Plasma catecholamine values were not significantly different between the two groups (all P > 0.05), but the estimated parasympathetic tone was higher in athletes (P=0.01). When data from all subjects were analyzed together, plasma E and NE correlated with PC₂₀ (r=0.39, P=0.005 and r=0.29, P < 0.005) but DA and SDNN did not (both P > 0.05). However, the ratios E/SDNN, NE/SDNN and DA/SDNN showed significant correlations with PC₂₀ (r=0.42, P < 0.01; r=0.33, P < 0.005 and r=0.31, P < 0.05, respectively). This study suggests that the sympatho-vagal balance may contribute to the increased AHR in the population studied but this influence alone cannot explain the higher prevalence of AHR in athletes. Accepted: 26 July 2000     

Respiratory Sinus Arrhythmia and Cardiovascular Responses to Stress

The parasympathetic nervous system provides mechanisms that could attenuate sympathetically mediated heart rate stress responses and might have even more general antagonistic actions on stress reactivity. Individuals characterized by higher levels of parasympathetic tone might, through such mechanisms, be less reactive when stimuli elicit sympathetically mediated responses. Respiratory sinus arrhythmia (RSA) is considered to be a noninvasive index of cardiac parasympathetic (vagal) tone. The present study investigated whether individual differences in RSA level at rest could predict variations among individuals in the magnitude of cardiovascular responses to psychological stress. None of the measures of resting respiratory sinus arrhythmia, derived from spectral analysis of beat-to-beat changes in resting heart rate, predicted the observed variations in cardiovascular task reactivity. However, scores reflecting respiratory sinus arrhythmia as the percentage of total heart rate variability (RSAnorm) were negatively correlated with blood pressure levels, both at rest and during the task. Furthermore, subjects with higher scores for RSAnorm demonstrated a faster adaptation of heart rate responses during stress, which suggests the development of parasympathetic antagonism to ongoing sympathetic arousal. Although a simple relationship between respiratory sinus arrhythmia and reactivity was not observed, these results encourage further investigation of RSA measures as psychophysiological indices of individual differences in parasympathetic (vagal) cardiac tone, or perhaps of general parasympathetic/sympathetic balance, which could modulate the expression of potentially pathogenic stress responses.     

超极化激活环核苷酸门控阳离子通道4、连接蛋白43和平足蛋白在小鼠胚胎心的表达与心传导系的发生

目的 探讨小鼠胚胎心传导系的发生机制。方法 用抗心肌肌球蛋白重链（MHC）、抗超极化激活环核苷酸门控阳离子通道4（HCN4）、抗缝隙连接蛋白43（CX43）和抗平足蛋白（podoplanin）抗体,对40只胚龄9~16d小鼠胚胎心进行连续石蜡切片并免疫组织化学或免疫荧光染色。结果 胚龄9d,较强的HCN4阳性表达集中在MHC阴性的静脉窦壁,随心脏发育,HCN4较强阳性表达逐渐向窦房结转移。胚龄11d开始,CX43阴性表达显示部位特异性。CX43阴性染色经窦房结沿右心房背侧壁和左、右静脉瓣向房室管背侧壁延伸。胚龄13d,左、右静脉瓣与房间隔底部融合后,进一步延续为房室管背侧壁发育中的CX43阴性染色的房室结,继而与室间隔顶部CX43阴性的房室束相连。胚龄9~10d,在MHC阳性心肌、心包腔背侧壁脏壁中胚层心肌前体细胞及静脉窦周间充质均显示podoplanin阳性表达。胚龄11~13d,podoplanin阳性间充质细胞沿心脏外表面扩展形成podoplanin阳性间皮样心外膜。结论 心脏发育早期,主起搏点位于静脉窦壁,起搏电位的产生早于收缩功能的发生。CX43阴性心肌是发育中的心传导系心肌,在胚龄11d即可观察到心传导系早期雏形。podoplanin参与促进心肌前体细胞向心肌细胞的分化。     

Electrophysiological effects of the antiarrhythmic agent GYKI-23107 in dogs

Cardiac electrophysiological properties of GYKI-23107, a new membrane stabilizing antiarrhythmic agent were studied in anaesthetized open-chest dogs. Epi- end endocardial electrograms (for sinus potential and for His bundle recording) were obtained during sinus rhythm and following atrial and ventricular pacing. The registration were performed under control conditions as well as five minutes after drug administration of 8 mg/kg slow i.v. or 20 minutes after 20 mg/kg intraduodenal administration respectively. GYKI-23107 did not influence significantly either the sinus cycles, PA-intervals, sinus node potentials, or the classical electrophysiological parameters of sinoatrial function as the corrected recovery time of the sinus node, sino-atrial conduction time or the secondary post-stimulation sinus cycles before and after vegetative blockade. Neither the AH intervals, anterograde Wenckebach period, nor ventriculo-atrial conduction time changed significantly. QRS duration, configuration and HV-intervals remained also unchanged after drug administration in doses which used in this study, and which seemed to be in therapeutic range. The agent did not influence significantly the effective refractory periods of the atrium and ventricle during sinus rhythm. This study suggest that the GYKI-23107 is not depressive on the anterograde (AV), retrograde (VA), intraventricular conduction and is slightly depressive on the intrinsic pacemaker properties.     

Influence of sympatho-vagal balance on airway responsiveness in athletes

The increased prevalence of airway hyperresponsiveness (AHR) observed among athletes suggests that high-level training may contribute to the development of AHR. We investigated the possible influence of the sympatho-vagal balance on this phenomenon in 40 athletes and 10 sedentary controls. Each subject filled out a respiratory questionnaire, had a methacholine challenge, and measurements were made of their baseline plasma catecholamines [epinephrine (E), norepinephrine (NE) and dopamine (DA)] as a reflection of sympathetic tone, and their heart rate variability (SDNN: standard deviation of all normal-to-normal intervals) as an indicator of parasympathetic tone. The athletes had a 45% prevalence of AHR (defined as PC20 < 16 mg/ml, where PC20 is the concentration of methacholine inducing a 20% fall in the forced expiratory volume in 1 s, FEV1) with a mean PC20 of 21.2 mg/ml compared with 10% prevalence (mean PC20: 74.4 mg/ml) in sedentary subjects (P < 0.01). Plasma catecholamine values were not significantly different between the two groups (all P > 0.05), but the estimated parasympathetic tone was higher in athletes (P = 0.01). When data from all subjects were analyzed together, plasma E and NE correlated with PC20 (r = 0.39, P = 0.005 and r = 0.29, P < 0.005) but DA and SDNN did not (both P > 0.05). However, the ratios E/SDNN, NE/SDNN and DA/SDNN showed significant correlations with PC20 (r = 0.42, P < 0.01; r = 0.33, P < 0.005 and r = 0.31, P < 0.05, respectively) This study suggests that the sympatho-vagal balance may contribute to the increased AHR in the population studied but this influence alone cannot explain the higher prevalence of AHR in athletes.     

Resting parasympathetic status and cardiovascular response to orthostatic and behavioral challenges in type I insulin-dependent diabetes mellitus

Alterations in cardiac autonomic innervation are commonly seen in individuals with diabetes mellitus. In this study, we used a cluster analysis to quantitatively separate individuals with Type I insulin-dependent diabetes mellitus (1DDM) on the basis of assessment of autonomic mediation of resting cardiac function and compared these two IDDM groups with nondiabetic control subjects. One group, termed IDDM-1, exhibited respiratory sinus arrhythmia and resting heart rale (HR) at the same level as controls. A second group, termed IDDM-2, displayed significantly reduced respiratory sinus arrhythmia and elevated resting HR, indicating reduced parasympathetic cardiac input. Noninvasive physiological assessment of the subjects’ response to orthostatic maneuvers (supine, seated, upright tilt) and behavioral stressors (speech preparation, speech talking, mirror tracing, cold pressor) revealed abnormalities in cardiovascular regulation in the IDDM groups. Specifically, under supine resting conditions the IDDM-2 group exhibited reduced myocardial contractility and stroke volume. HR was accelerated in these subjects but not enough to compensate for the decreased stroke volume, and therefore cardiac output was not maintained at normal levels. Consequently, total peripheral resistance and hlood pressure were elevated in thcse subjects. Thus. for the IDDM-2 subjects, these data sugges that blood flow to the periphery is being sacrificed In maintain flow to the heart, lungs, and brain, which cannot sustain themselves anaerobically. The IDDM subjects, when compared with the control subjects, responded with similar magnitude and pattern of cardiovascular response to the behavioral stressors that selectively challenged the heart, vasculature, or both. However, the cardiovascular pattern produced by the IDDM subjects to the seated and uprigh postural challenges suggests that the IDDM-1, and to a certain extent the IDDM-2 subjects, evidenced difficulty in regulating vasomotor and/or venomotor tone to maintain blood pressure levels. Therefore, this study demonstrates a quantitative method for assessing resting parasympathetic status that distinguishes a group of IDDM subjects with abnormal resting cardiovascular regulation and response to challenge. This work was supported by Grants POI-HL36588 and T32-HL07426 from the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Public Health Service     

Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation.     

Invasive electrophysiological evaluation of patients with sleep apnoea-associated ventricular asystole—methods and preliminary results

SUMMARY  Twelve patients (aged 48 ± 12 y) with ventricular asystole of >3s due to complete atrioventricular (AV) block ( n = 8), sinoatrial (SA) block or sinus node arrest ( n = 3) or both ( n = 1) associated with obstructive sleep apnoea underwent invasive electrophysiological evaluation of sinus node function and AV conduction properties before and after administration of atropine (0.02 mg kg^-1). Ventricular asystole lasted for 5.9 ± 2.8 s (range 3.1–13 s). Sinus node function was assessed by measurement of sinus node recovery time, sinoatrial conduction time, and the response of sinus rate to atropine. Parameters of AV-conduction assessment included AH- and HV-intervals, AV- and VA-Wenckebach periods, and effective refractory period of the AV node before and after atropine. Sinus node function was normal in 11 of the 12 study patients and moderately abnormal in 1 patient. AV-nodal function was normal in 8 patients and moderately abnormal in 4 patients. A slightly prolonged HV-interval (59–63 ms) was present in 6 patients. Intra- or infra His block was not observed in any patient. In conclusion, normal or only moderately abnormal electrophysiological findings in patients with sleep apnoea-associated ventricular asystole suggest that a neurally mediated cardioinhibitory reflex may cause ventricular asystole in these patients. This sleep apnoea-triggered 'vasovagal' reflex may unmask pre-existing mild to moderate structural abnormalities of the AV conduction system.     

A new sign of parasympaticotonia in trained athletes

Summary The amount of eccrine sweat induced by pilocarpine at rest is significantly higher in 10 endurance cyclists than in 13 wrestlers, 29 football-players and 129 normal subjects. Also in 29 football-players a partial relation between the degree of bradycardia, ability to perform work and the amount of sweat at rest was found. A significant (0.05 < P < 0.01) relation between bradycardia and the amount of effort sweat has been detected.Those findings are explained as a new sign of increased tone of the parasympathetic nervous system in trained athletes.     

Cardiac pacemakers in absence of the SA node: responses to exercise and autonomic blockade.

Surgical excision of the sinoatrial node, verified histologically, is followed by a supraventricular (atrial) rhythm in both resting and exercising dog whether anesthetized or conscious. The ECG is characterized by a definitive P wave and associated atrial electrograms. Waxing and waning in heart rate, generally referred to as sinus arrhythmia continues in the awake animal after complete excision of the SA node. This arrhythmia is responsive to both adrenergic and cholinergic interventions, thus indicating the presence of both sympathetic and parasympathetic regulation of subsidiary atrial pacemaking tissues.     

Cardiac conduction system in the chicken: Gross anatomy plus light and electron microscopy

Twenty-three chicken hearts were used to study the cardiac conduction system by light and electron microscopy. In addition to a sinus node, atrioventricular node (AVN), His bundle, left and right bundle branches (LBB, RBB), the chicken also has an AV Purkinje ring and a special middle bundle branch (MBB). The sinus node lies near the base of the lower portion of the right sinoatrial valve. The AV node is just above the tricuspid valve and anterior to the coronary sinus. The His bundle descends from the anterior and inferior margin of the AV node into the interventricular septum, then dividing into right, left and middle branches some distance below the septal crest. The middle bundle branch turns posteriorly toward the root of the aorta. The AV Purkinje ring originates from the proximal AV node and then encircles the right AV orifice, joining the MBB to form a figure-of-eight loop. The chicken conduction system contains four types of myocytes: (1) The P cell is small and rounded, with a relatively large nucleus and sparse myofibrils. (2) The transitional cell is slender and full of myofibrils. (3) The Purkinje-like cell resembles the typical Purkinje cell, but is smaller and darker. (4) The Purkinje cell is found in the His bundle, its branches, and the periarterial and subendocardial Purkinje network. © 1993 Wiley-Liss, Inc.     

Strong desmin immunoreactivity in the myocardial sleeves around pulmonary veins,superior caval vein and coronary sinus supports the presumed arrhythmogenicity of these regions

Myocardial sleeve around human pulmonary veins plays a critical role in the pathomechanism of atrial fibrillation. Besides the well-known arrhythmogenicity of these veins, there is evidence that myocardial extensions into caval veins and coronary sinus may exhibit similar features. However, studies investigating histologic properties of these structures are limited. We aimed to investigate the immunoreactivity of myocardial sleeves for intermediate filament desmin, which was reported to be more abundant in Purkinje fibers than in ventricular working cardiomyocytes. Sections of 16 human (15 adult and 1 fetal) hearts were investigated. Specimens of atrial and ventricular myocardium, sinoatrial and atrioventricular nodes, pulmonary veins, superior caval vein and coronary sinus were stained with anti-desmin monoclonal antibody. Intensity of desmin immunoreactivity in different areas was quantified by the ImageJ program. Strong desmin labeling was detected at the pacemaker and conduction system as well as in the myocardial sleeves around pulmonary veins, superior caval vein, and coronary sinus of adult hearts irrespective of sex, age, and medical history. In the fetal heart, prominent desmin labeling was observed at the sinoatrial nodal region and in the myocardial extensions around the superior caval vein. Contrarily, atrial and ventricular working myocardium exhibited low desmin immunoreactivity in both adults and fetuses. These differences were confirmed by immunohistochemical quantitative analysis. In conclusion, this study indicates that desmin is abundant in the conduction system and venous myocardial sleeves of human hearts.     

Association between cardiac disorders and a decades-previous history of diphtheria

A long, prior history of diphtheria is common among middle-aged and elder European adults. The aim of the present study was to determine whether the risk of reduced ventricular function and impaired intraventricular conduction is increased in individuals with a history of diphtheria. A study population of 2,480 subjects (1,222 women) aged 45 years or older who were recruited for the Study of Health in Pomerania were available for the present analyses. Left ventricular function was assessed by echocardiography. Intraventricular conduction blocks were diagnosed using electrocardiograms. Multivariable analyses revealed that individuals with a history of diphtheria had neither an increased odds for reduced fractional shortening (OR 1.21, 95% CI 0.69–2.11; p = 0.51) nor an increased odds for intraventricular conduction blocks (OR 0.90, 95% CI 0.55–1.46; p = 0.67). However, regression models revealed two-way interactions between the exposure variable and hypertension with respect to both endpoints. A history of diphtheria increased the odds for both endpoints in normotensive but not in hypertensive individuals. The findings show that a history of diphtheria several decades previously in a patient is a risk marker for reduced cardiac function and impaired intraventricular conduction in individuals at low risk for these disorders.     

Autonomic innervation of the human cardiac conduction system: changes from infancy to senility--an immunohistochemical and histochemical analysis

In order to study the changes in the pattern of autonomic innervation of the human cardiac conduction system in relation to age, the innervation of the conduction system of 24 human hearts (the age of the individuals ranged from newborn to 80 years), freshly obtained at autopsy, was evaluated by a combination of immunofluorescence and histochemical techniques. The pattern of distribution and density of nerves exhibiting immunoreactivity against protein gene product 9.5 (PGP), a general neural marker, dopamine beta-hydroxylase (DBH) and tyrosine hydroxylase (TH), indicators for presumptive sympathetic neural tissue, and those demonstrating positive acetylcholinesterase (AChE) activity, were studied. All these nerves showed a similar pattern of distribution and developmental changes. The density of innervation, assessed semiquantitatively, was highest in the sinus node, and exhibited a decreasing gradient through the atrioventricular node, penetrating and branching bundle, to the bundle branches. Other than a paucity of those showing AChE activity, nerves were present in substantial quantities in infancy. They then increased in density to a maximum in childhood, at which time the adult pattern was achieved and then gradually decreased in density in the elders to a level similar to or slightly less than that in infancy. In contrast, only scattered AChE-positive nerves were found in the sinus and atrioventricular nodes, but were absent from the bundle branches of the infant heart, whereas these conduction tissues themselves possessing a substantial amount of pseudocholinesterase. During maturation into adulthood, however, the conduction tissues gradually lost their content of pseudocholinesterase but acquired a rich supply of AChE-positive nerves, comparable in density to those of DBH and TH nerves. The decline in density of AChE-positive nerves in the conduction tissues in the elders was also similar to those of DBH and TH nerves. Our findings of initial sympathetic dominance in the neural supply to the human cardiac conduction system in infancy, and its gradual transition into a sympathetic and parasympathetic codominance in adulthood, correlate well with the physiologic alterations known to occur in cardiac rate during postnatal development. The finding of reduction in density of innervation of the conduction tissue with ageing is also in agreement with clinical and electrophysiological findings such as age-associated reduction in cardiac response to parasympathetic stimulation. Finally, our findings also support the hypothesis that, in addition to the para-arterial route, the parafascicular route of extension along the conduction tissue constitutes another pathway for the innervation of the conduction system of the human heart during development.     

Erythrocyte cations and Na+,K+-ATPase pump activity in athletes and sedentary subjects

Summary The chronic effect of training on intraerythrocyte cationic concentrations and on red cell Na⁺,K⁺-ATPase pump activity was studied by comparing well-trained athletes with sedentary subjects at rest. Also the acute effect of a 50-min cross-country run on these erythrocyte measurements was studied in the athletes. At rest the intraerythrocyte potassium concentration was increased (P<0.01) in the athletes compared to that of the control subjects. The intraerythrocyte concentrations of sodium and magnesium and red cell Na⁺, K⁺-ATPase pump activity were, however, similar in the trained and the untrained subjects.As compared with the resting condition, the intraerythrocyte potassium concentration was decreased (P<0.05) after exercise in the athletes, and this was accompanied by a minor increase in the intraerythrocyte sodium concentration. Red cell Na⁺,K⁺-ATPase pump activity was slightly increased (P<0.05) after exercise.     

Persistent atrioventricular block in Lyme borreliosis

Summary Cardiac manifestations are reported in 0.3%–4.0% of European patients withBorrelia burgdorferi (B.b.) infection. Usually symptoms disappear within 6 weeks. We report a case with persistent impairment of atrioventricular (AV) conduction. Diagnosis was confirmed by demonstration of IgM antibodies and increase of IgG antibody titers against B.b. in serum, by isolation of the spirochete from skin biopsy material and by the typical clinical combination of erythema migrans, Bannwarth syndrome (meningoradiculitis), and complete heart block. Despite immediate antibiotic therapy with ceftriaxone, first degree AV block and second degree block Wenckebach with atrial pacing at 100 beats/minute persisted for 2 years. We conclude, that Lyme carditis can cause long-standing or irreversible AV conduction defects despite adequate and early antimicrobial therapy.Abbreviations AV atrioventricular - AVt atrioventricular time - B. burgdorferi Borrelia burgdorferi - CSF cerebrospinal fluid - ECG electrocardiogram - ESR erythrocyte sedimentation rate - FRG Federal Republic of Germany - I. dammini/ricinus Ixodes dammini/ricinus - IgG immunoglobulin G - IgM immunoglobulin M     

Autonomic innervation of the human cardiac conduction system: Changes from infancy to senility—An immunohistochemical and histochemical analysis

In order to study the changes in the pattern of autonomic innervation of the human cardiac conduction system in relation to age, the innervation of the conduction system of 24 human hearts (the age of the individuals ranged from newborn to 80 years), freshly obtained at autopsy, was evaluated by a combination of immunofluorescence and histochemical techniques. The pattern of distribution and density of nerves exhibiting immunoreactivity against protein gene product 9.5 (PGP), a general neural marker, dopamine β‐hydroxylase (DBH) and tyrosine hydroxylase (TH), indicators for presumptive sympathetic neural tissue, and those demonstrating positive acetylcholinesterase (AChE) activity, were studied. All these nerves showed a similar pattern of distribution and developmental changes. The density of innervation, assessed semiquantitatively, was highest in the sinus node, and exhibited a decreasing gradient through the atrioventricular node, penetrating and branching bundle, to the bundle branches. Other than a paucity of those showing AChE activity, nerves were present in substantial quantities in infancy. They then increased in density to a maximum in childhood, at which time the adult pattern was achieved and then gradually decreased in density in the elders to a level similar to or slightly less than that in infancy. In contrast, only scattered AChE‐positive nerves were found in the sinus and atrioventricular nodes, but were absent from the bundle branches of the infant heart, whereas these conduction tissues themselves possessing a substantial amount of pseudocholinesterase. During maturation into adulthood, however, the conduction tissues gradually lost their content of pseudocholinesterase but acquired a rich supply of AChE‐positive nerves, comparable in density to those of DBH and TH nerves. The decline in density of AChE‐positive nerves in the conduction tissues in the elders was also similar to those of DBH and TH nerves. Our findings of initial sympathetic dominance in the neural supply to the human cardiac conduction system in infancy, and its gradual transition into a sympathetic and parasympathetic codominance in adulthood, correlate well with the physiologic alterations known to occur in cardiac rate during postnatal development. The finding of reduction in density of innervation of the conduction tissue with ageing is also in agreement with clinical and electrophysiological findings such as age‐associated reduction in cardiac response to parasympathetic stimulation. Finally, our findings also support the hypothesis that, in addition to the para‐arterial route, the parafascicular route of extension along the conduction tissue constitutes another pathway for the innervation of the conduction system of the human heart during development. Anat Rec 264:169–182, 2001. © 2001 Wiley‐Liss, Inc.     

Thermoregulatory responses of paraplegic and able-bodied athletes at rest and during prolonged upper body exercise and passive recovery

The thermoregulatory responses of ten paraplegic (PA; T3/4-L4) and nine able-bodied (AB) upper body trained athletes were examined at rest and during prolonged arm-cranking exercise and passive recovery. Exercise was performed for 90 min at 80% peak heart rate, and at 21.5 (1.7)°C and 47.0 (7.8)% relative humidity on a Monark cycle ergometer (Ergomedic 814E) adapted for arm exercise. Mean peak oxygen uptake values for the PA and AB athlete groups were 2.12 (0.41) min⁻¹ and 3.19 (0.38) l · min⁻¹, respectively (P<0.05). At rest, there was no difference in aural temperature between groups [36.2 (0.4)°C for both groups]. However, upper body skin temperatures for the PA athletes were approximately 1.0 °C warmer than for the AB athletes, whereas lower body skin temperatures were cooler than those for the AB athletes (1.3 °C and 2.7 °C for the thigh and calf, respectively). Upper and lower body skin temperatures for the AB athletes were similar. During exercise, blood lactate peaked after 15 min of exercise for both groups [3.33 (1.26) mmol · l⁻¹ and 4.30 (1.03) mmol · l⁻¹ for the PA and AB athletes, respectively, P<0.05] and decreased throughout the remainder of the exercise period. Aural temperature increased by 0.7 (0.5)°C and 0.6 (0.4)°C for the AB and PA athletes, respectively. Calf skin temperature for the PA athletes increased during exercise by 1.4 (2.8)°C (P<0.05), whereas a decrease of 0.8 (2.0)°C (P<0.05) was observed for the AB athletes. During the first 20 min of recovery from exercise, the calf skin temperature of the AB athletes decreased further [−2.6 (1.3)°C; P<0.05]. Weight losses and changes in plasma volume were similar for both groups [0.7 (0.5) kg and 0.7 (0.4) kg; 5.4 (4.9)% and 9.7 (6.2)% for the PA and AB athletes, respectively]. In conclusion, the results of this study suggest that the PA athletes exhibit different thermoregulatory responses at rest and during exercise and passive recovery to those of upper body trained AB athletes. Despite this, during 90 min of arm-crank exercise in a cool environment, the PA athletes appeared to be at no greater thermal risk than the AB athletes. Accepted: 7 May 1997     

Nkx2.5‐negative myocardium of the posterior heart field and its correlation with podoplanin expression in cells from the developing cardiac pacemaking and conduction system

Recent advances in the study of cardiac development have shown the relevance of addition of myocardium to the primary myocardial heart tube. In wild‐type mouse embryos (E9.5–15.5), we have studied the myocardium at the venous pole of the heart using immunohistochemistry and 3D reconstructions of expression patterns of MLC‐2a, Nkx2.5, and podoplanin, a novel coelomic and myocardial marker. Podoplanin‐positive coelomic epithelium was continuous with adjacent podoplanin‐ and MLC‐2a‐positive myocardium that formed a conspicuous band along the left cardinal vein extending through the base of the atrial septum to the posterior myocardium of the atrioventricular canal, the atrioventricular nodal region, and the His‐Purkinje system. Later on, podoplanin expression was also found in the myocardium surrounding the pulmonary vein. On the right side, podoplanin‐positive cells were seen along the right cardinal vein, which during development persisted in the sinoatrial node and part of the venous valves. In the MLC‐2a‐ and podoplanin‐positive myocardium, Nkx2.5 expression was absent in the sinoatrial node and the wall of the cardinal veins. There was a mosaic positivity in the wall of the common pulmonary vein and the atrioventricular conduction system as opposed to the overall Nkx2.5 expression seen in the chamber myocardium. We conclude that we have found podoplanin as a marker that links a novel Nkx2.5‐negative sinus venosus myocardial area, which we refer to as the posterior heart field, with the cardiac conduction system. Anat Rec, 290:115–122, 2007. © 2006 Wiley‐Liss, Inc.