- / Our purpose was to assess the function of fast somatic nerve fibres, the sympathetic sudomotor system and the function of parasympathetic heart con-trol in patients with partial or generalized seizures, receiving various therapeu-tic regimes, by means of clinical routine neurophysiology. We studied 73 pati-ents (mean age 37,7±12,9 years) and 73 matched healthy controls by clinical and electrophysiological examinations. To assess the function of fast somatic nerve fibres we studied the motor conduction of the peroneal nerve (distal latency, amplitude of action potential, conduction velocity) and the sensory conduction of the ulnar and sural nerves (amplitude of action potential, conduction velocity) in all patients and controls. To assess the sympathetic sudomotor system we studied the sympathetic skin response (SSR) elicited in the hand and foot by electrical and magnetic stimulation. The electrical stimulation applied in all patients and controls but the magnetic stimulation applied in 61 patients and 72 contols (exepted pati-ents and controls wich had something metallic in their body such as surgical clips, pace-maker, metallic valve). To assess the function of parasympathetic heart contol all the patients and the controls were subjected to a battery of three cardiovascular tests: a) heart rate variability during six deep breaths/min [algorithm:(max-min)R-R Interval x 100/mean R-R Interval] b) Valsava maneuver (ratio of the shortest RR interval during phase II to the longest RR interval in phase IV) c) heart rate response to standing up(ratio 30th beat/15th beat). Compared to controls, patients showed a significant abnormality of motor (prolongation of distal latency) and sensory (slowing of ulnar conduction velo-city, reduction of amplitude of sural action potential) conduction. Reason and duration of epilepsy, type and frequency of seizyre and polytherapy didn’t ap-pear to have a negative effect on motor or sensory conduction. Particular antiepileptic drugs, oxcarbazepine, phenytoin, topiramate, lebetiracetam, ap-peared to have a negative effect on sensory conduction. Clinical sings of neu-ropathy were disclosed in 13,7% of patients, while at least one abnormal sen-sory parameter was evident in 11%. In the patient group as opposed to the control group, there was a latency prolongation of sympathetic skin response recorded in hand and foot to elec-trical and magnetic stimulation. At least one SSR abnormality was shown in 28 (38,3%) patients and 9 (12,3%) of these had absent SSR from the hand or/and the food with electrical or/and magnetic stimulation. Reason & duration of epi-lepsy, type, frequency & age at onset of seizure, time from last seizure and po-lytherapy didn’t appear to have a negative effect on sympathetic sudomotor function. Particular antiepileptic drugs, topiramate and phenytoin, appeared to have a negative effect on sympathetic sudomotor function. Finally, the patient group showed significantly difference in all parasympa-thetic parameters studied compared to controls. Overall, 42,2% of patients had abnormal measurement in at least one of these parameters and [algorithm:(max-min)R-R Interval x 100/mean R-R Interval] was the most fre-quently abnormal one (31,5% of patients). Reason & duration of epilepsy, fre-quency, type & age at onset of seizure, time from last seizure and polytherapy didn’t appear to have a negative effect. Particular antiepileptic drugs, oxcarba-zepine and phenytoin appeared to have a negative effect on fuction of para-sympathetic heart control. Overall, 50 of the 73 patients had abnormal measurement in at least one of all parameters wich we studied. Our results suggested that simple neurophysiological tests, suitable for screening purposes, were able to demomstrate abnormalities of the fast so-matic fibers in peripheral nerves, of the sympathetic sudomotor system and of the parasympathetic heart control.

Orientador: Carlos Marcelo Pastre / Banca: Luiz Carlos Marques Vanderlei / Banca: Moacir Fernandes de Godoy / Resumo: O sistema nervoso autônomo (SNA) desempenha um papel importante na regulação dos processos fisiológicos do organismo humano tanto em condições normais quanto patológicas. Dentre as técnicas utilizadas para sua avaliação, a variabilidade da frequência cardíaca (VFC) tem emergido como uma medida simples e não-invasiva dos impulsos autonômicos, representando um dos mais promissores marcadores quantitativos do balanço autonômico. A VFC descreve as oscilações no intervalo entre batimentos cardíacos consecutivos (intervalos R-R), assim como oscilações entre frequências cardíacas instantâneas consecutivas. Trata-se de uma medida que pode ser utilizada para avaliar a modulação do SNA sob condições fisiológicas, tais como em situações de vigília e sono, diferentes posições do corpo, treinamento físico, e também em condições patológicas. Mudanças nos padrões da VFC fornecem um indicador sensível e antecipado de comprometimentos na saúde. Uma alta variabilidade na frequência cardíaca é sinal de boa adaptação, caracterizando um indivíduo saudável, com mecanismos autonômicos eficientes, enquanto que, baixa variabilidade é frequentemente um indicador de adaptação anormal e insuficiente do SNA, implicando a presença de mau funcionamento fisiológico no indivíduo. Diante da sua importância como um marcador que reflete a atividade do SNA sobre o nódulo sinusal e como uma ferramenta clínica para avaliar e identificar comprometimentos na saúde, este artigo revisa aspectos conceituais da VFC, dispositivos de mensuração, métodos de filtragem, índices utilizados para análise da VFC, limitações de utilização e aplicações clínicas da VFC. / Abstract: Autonomic nervous system (ANS) plays an important role in the regulation of the physiological processes of the human organism during normal and pathological conditions. Among the techniques used in its evaluation, the heart rate variability (HRV) has arising as a simple and non-invasive measure of the autonomic impulses, representing one of the most promising quantitative markers of the autonomic balance. The HRV describes the oscillations in the interval between consecutive heart beats (RR interval), as well as the oscillations between consecutive instantaneous heart rates. It is a measure that can be used to assess the ANS modulation under physiological conditions, such as wakefulness and sleep conditions, different body positions, physical training and also pathological conditions. Changes in the HRV patterns provide a sensible and advanced indicator of health involvements. Higher HRV is a signal of good adaptation and characterizes a health person with efficient autonomic mechanisms, while lower HRV is frequently an indicator of abnormal and insufficient adaptation of the autonomic nervous system, provoking poor patient's physiological function. Because of its importance as a marker that reflects the ANS activity on the sinus node and as a clinical instrument to assess and identify health involvements, this study reviews conceptual aspects of the HRV, measurement devices, filtering methods, indexes used in the HRV analyses, limitations in the use and clinical applications of the HRV. / Mestre

Objetivo. Verificar se as características espectrais dos eletrogramas atriais (EgA) em ritmo sinusal (RS) se correlacionam com a presença de gânglios parassimpáticos cardíacos. Materiais e Resultados. Treze pacientes encaminhados para submeter-se a ablação de fibrilação atrial (FA) foram incluídos de forma prospectiva. Previamente ao início da ablação, realizou-se o registro de EgA em RS em uma série de regiões anatômicas pré-determinadas, seguindo-se uma ordem sequencial. Em seguida, aplicou-se estímulos elétricos de alta frequência (20 Hz de frequência, amplitude de 100 V e duração de pulso de 4 ms), nos mesmos locais. Uma resposta vagal evocada foi definida como um súbito aumento no intervalo RR ou a indução de bloqueio na condução átrio-ventricular imediatamente após a aplicação do estímulo de alta-frequência (EAF). Procedeu-se à análise espectral dos sinais atriais em RS registrados, com amostragem de 1000 Hz, janela Hanning. No total, 1488 EgA oriundos de 186 locais anatômicos foram registrados, sendo 129 de regiões com resposta vagal negativa e 57 correspondentes a regiões de resposta vagal positiva. A duração do eletrograma e o número de deflecções foram similares nos pontos com resposta vagal positiva e negativa. A densidade de potência espectral em locais de resposta vagal positiva, no entanto, foi menor entre 26 e 83 Hz, e maior entre 107 e 200 Hz, comparados com os locais de resposta negativa. A área sobre a curva entre 120 e 170 Hz normalizada para a área total do espectro foi testada como um novo parâmetro diagnóstico. A análise de curva ROC demonstrou que o valor area 120-170 / area total > 0,14 foi capaz de identificar locais de inervação vagal com sensibilidade de 70,9% e especificidade de 72,1%. Conclusão. A análise espectral de sinais atriais durante RS é um método factível e simples de mapear os locais de inervação parassimpática cardíaca, sem a necessidade de qualquer tipo de estimulação / Objective. To verify whether spectral components of atrial electrograms (AE) during sinus rhythm (SR) correlate with cardiac ganglionated plexus (GP) sites. Methods and Results. Thirteen patients undergoing atrial fibrillation (AF) ablation were prospectively enrolled. Prior to radio frequency application, endocardial AE were recorded with a sequential point-by-point approach. Electrical stimuli were delivered at 20 Hz, amplitude 100 V, and pulse width of 4 msec. A vagal response was defined as a high-frequency stimulation (HFS) evoked AV block or a prolongation of RR interval. Spectral analysis was performed on single AE during SR, sampling rate of 1000 Hz, Hanning window. Overall, 1488 SR electrograms were analyzed from 186 different left atrium sites, 129 of them corresponding to negative vagal response sites and 57 to positive response sites. The electrogram duration and the number of deflections were similar in positive and negative response sites. Spectral power density of sites with vagal response was lower between 26 and 83 Hz and higher between 107 and 200 Hz compared with negative response sites. The area between 120 and 170 Hz normalized to the total spectrum area was tested as a diagnostic parameter. ROC curve analysis demonstrated that an area 120-170 / area total value > 0,14 identified vagal sites with 70,9% sensitivity and 72,1% specificity. Conclusions. Spectral analysis of AE during SR is feasible and simple method of mapping the cardiac autonomic nervous system (ANS), with no stimulation required

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-07-01T17:59:35Z No. of bitstreams: 1 tiagopecanhadeoliveira.pdf: 3493723 bytes, checksum: 21c1c1d4d09dfd5a36766f8c4d975aa6 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-07-13T16:05:45Z (GMT) No. of bitstreams: 1 tiagopecanhadeoliveira.pdf: 3493723 bytes, checksum: 21c1c1d4d09dfd5a36766f8c4d975aa6 (MD5) / Made available in DSpace on 2016-07-13T16:05:45Z (GMT). No. of bitstreams: 1 tiagopecanhadeoliveira.pdf: 3493723 bytes, checksum: 21c1c1d4d09dfd5a36766f8c4d975aa6 (MD5) Previous issue date: 2012-03-07 / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / O exercício físico promove uma série de alterações fisiológicas no organismo, provocando, reflexamente, retirada do tônus vagal e elevação da ativação simpática para o coração. Este conjunto de respostas está por trás da elevação da frequência cardíaca (FC) que ocorre em qualquer tipo de exercício físico. Logo após o término do exercício, a FC cai exponencialmente, e esta queda é mediada, predominantemente, pela reativação vagal. Na medida em que a recuperação prossegue, a queda da FC é gradual e sustentada. Nesta fase, além da reativação vagal, há também a retirada do tônus simpático. A investigação da magnitude da recuperação da frequência cardíaca pós-exercício, portanto, é uma forma de avaliar a integridade autonômica cardiovascular. Recentemente, estudos têm proposto métodos adequados para a avaliação da Variabilidade da Frequência Cardíaca (VFC) no período da recuperação pós-exercício. Esta ferramenta permite um entendimento complementar dos processos relacionados à recuperação autonômica cardíaca e, por conta disso, possui potencial relevância clínica. A presente dissertação centrou-se no estudo da recuperação autonômica cardíaca pósexercício. No primeiro estudo, propusemos um método de identificação do tempo necessário para a reativação vagal plena pós-exercício e verificamos a influência do nível de treinamento físico neste tempo. Participaram deste estudo 18 indivíduos jovens, divididos em um grupo de “baixo nível de treinamento físico” e outro de “alto nível de treinamento físico”. Foi observada reativação vagal plena mais rápida no segundo grupo. O segundo estudo propôs um novo método de identificação do tempo necessário para a reativação vagal plena; verificou a influência da intensidade do exercício físico neste tempo e; comparou os resultados obtidos por este novo método com os obtidos pelo método proposto no primeiro estudo. Participaram deste estudo 10 indivíduos jovens e sedentários. A reativação vagal plena foi mais lenta após o exercício intenso em comparação ao exercício moderado, independente do método utilizado. No entanto, houve diferença no tempo da reativação vagal plena entre os métodos utilizados e são necessários mais estudos para definir qual o melhor método. No terceiro estudo verificamos a influência da intensidade do exercício no comportamento de 24 horas da frequência cardíaca e da Variabilidade da Frequência Cardíaca Pós-Exercício. Dividimos as 24 horas pós-exercício em: período de laboratório, com duração de 1 hora e; período ambulatorial, com duração de 23 horas. Observamos maiores valores de FC e menores valores de VFC, durante a primeira hora da recuperação, após o exercício intenso, em comparação ao exercício moderado; e menores valores do índice HF, no período do sono, após o exercício intenso, em comparação ao exercício moderado e à linha de base. Conclui-se, após todos os trabalhos desta dissertação, que o nível de treinamento físico e a intensidade do exercício físico exercem influência sobre a recuperação autonômica cardíaca e que o método de identificação da reativação vagal plena parece ser adequado para avaliação do impacto do exercício sobre a modulação vagal cardíaca pós-exercício. A avaliação da VFC no período do sono também se mostrou interessante e deve ser melhor investigada para posterior aplicação prática. / The physical exercise promotes a series of physiologic changes in the human organism, causing, reflexly, vagal tone withdrawal and rising of the sympathetic activation to the heart. This set of responses is behind the heart rate (HR) rising, that occurs in any type of physical exercise. Immediately after the exercise end, the HR goes down exponentially, and this fall is mediated, predominantly, by the vagal reactivation. According as the recovery continues, the fall of the HR is gradual and sustained. At this phase, further the vagal reactivation, there is also the sympathetic tonus withdrawal. The investigation of the post-exercise recovery heart rate magnitude, so, is a way to assess the autonomic cardiovascular integrity. Recently, studies have proposed adequate methods to assess the Heart Rate Variability in the post-exercise recovery period. This appliance allows a complementary understanding of the cardiac autonomic recovery related procedures, and because of that, has potential clinical relevance. The present thesis focused on the study of the postexercise autonomic cardiac recovery. In the first study, we proposed a identification method of the time required to the post-exercise full vagal reactivation and it was verified the influence of the training level at this time. 18 young subjects participated in the study; they were divided into a group of “low training level” and other group of “high training level”, there was observed faster full vagal reactivation in the second group. In the second study, we proposed a new identification method of the time required to the post-exercise full vagal reactivation, the influence of the physical exercise at this time was verified and the results of the new method were compared to the ones of the first study method. 10 young and sedentary subjects participated in this study. The full vagal reactivation was slower after the intense exercise compared to the moderate exercise, independent of the method used. However, there was difference in the full vagal reactivation time between the methods used and more studies are necessary to define what is the best method. In the third study we verified the influence of the physical exercise intensity in the 24 hours heart rate and the post-exercise heart rate variability behavior. We divided the 24 hours into: lab period, with 1 hour of duration and; ambulatory period, with 23 hours of duration. We observed higher values of HR and lower values of HRV, during the recovery first hour, after intense exercise, compared to the moderate exercise; and lower HF-HRV values, at sleep period, after intense exercise, compared to the moderate exercise and baseline. In conclusion, the physical training level and the physical exercise intensity influence the cardiac autonomic recovery and the identification of full vagal reactivation method can be appropriate to assess the exercise impact on the postexercise cardiac vagal modulation. The assess of the HRV in the sleep period also seemed to be interesting and have to be better investigated to subsequent practical application.

Parmi les facteurs intervienant dans la régulation et le maintien du fonctionnement d'organes, le système nerveux autonome et la microcirculation jouent un rôle prépondérant. Chez les patients critiques, comme les patients en sepsis, des altérations de la balance sympatho-vagale et de la perfusion tissulaire peuvent survenir et avoir des conséquences majeures en matière de morbidité et mortalité. La mise en oeuvre de méthodes de détection précoces de ces perturbations pourrait donc contribuer à améliorer la survie des patients à risque. En effet, le suivi des paramètres hémodynamiques, comme classiquement réalisé lors de réanimation, peut s'avérer insuffisant pour détecter des altérations de perfusion tissulaire : lors de sepsis, des altérations microcirculatoires peuvent persister en dépit de la normalisation des paramètres macrocirculatoires et sont associées à un mauvais pronostic. Eu égard à la présence de dysfunctions microcirculatoires et du système nerveux autonome chez les patients critiques, ce travail de recherche s'est proposé d'évaluer l’impact de modulateurs du système sympathique sur la balance sympatho-vagale et la microcirculation. Pour ce faire, nous avons travaillé avec des modèles animaux et des animaux admis en centre hospitalier universitaire vétérinaire. Le suivi du système nerveux autonome s'est basé sur un nouvel index de mesure du tonus parasympathique (Parasympathetic Tone Activity ou PTA). En parallèle, la microcirculation a été évaluée par vidéomicroscopie (SDF, Sidestream Dark Field imaging). L'index PTA a démontré une performance correcte pour prédire les réactions hémodynamiques chez les chiens anesthésiés. Il a aussi permis de détecter une altération de la balance sympathique chez les chevaux admis pour une chirurgie de colique ainsi qu’une altération de la microcirculation en dépit des manoeuvres de réanimation. Les études précliniques sur l’impact de la perfusion d’esmolol et de dexmédétomidine dans un modèle porcin septique ont montré que, malgré leurs effets hémodynamiques potentiels, ces agents n’ont pas eu d’effet négatif sur la microcirculation. Ainsi, les résultats de ce travail suggèrent un effet bénéfique des modulateurs du système nerveux sympathique sur la microcicultion mais nécessite d'être confirmé à plus grande échelle / Among the factors involved in the regulation and maintenance of the organs’ functioning, the autonomic nervous system and the microcirculation play a preponderant role. In critical patients, such as septic patients, alterations in the sympathovagal balance and tissue perfusion may occur and have major consequences of morbidity and mortality. The implementation of early detection methods for these disturbances could therefore contribute to improve the survival of patients at risk. Indeed, the monitoring of hemodynamic parameters, as conventionally performed during resuscitation, may be insufficient to detect tissue perfusion alterations: during sepsis, microcirculatory changes may persist despite the normalization of macrocirculatory parameters and are associated with a bad prognosis. With regard to the presence of microcirculatory dysfunctions and autonomic nervous system alterations in critical patients, this research project proposed to evaluate the impact of modulators of the sympathetic system on the sympatho-vagal balance and microcirculation. In order to achieve this, we worked on animal models and animals admitted to the faculty’s veterinary hospital center. Monitoring of the autonomic nervous system was based on a new Parasympathetic Tone Activity (PTA) index. In parallel, the microcirculation was evaluated by videomicroscopy (SDF, Sidestream Dark Field imaging). The PTA index demonstrated a good performance in predicting hemodynamic reactions in anesthetized dogs. It also detected disturbances of the sympathetic balance in horses admitted for colic surgery as well as an alteration of microcirculation despite resuscitation maneuvers. Preclinical studies on the impact of esmolol and dexmedetomidine infusion in a septic swine model showed that, despite their potential hemodynamic effects, these agents did not have a negative effect on the microcirculation. Thus, these findings suggest a beneficial effect of the modulators of the sympathetic nervous system on the microcicultion, however, these resutls should be confirmed on a larger scale

Individual differences in autonomic nervous system responsiveness have been linked to a variety of physical disorders and personality and behavioral tendencies. The present study attempted to correlate specific personality characteristics hypothesized to be associated with either sympathetic or parasympathetic dominance based on the work of M. A. Wenger. The Clinical Analysis Questionnaire Personality Inventory, a physical disorders questionnaire, a self-report stress measure, and seven psychophysiologic tests were administered to 60 undergraduate students in an introductory psychology class at North Texas State University. The results provided limited support for the hypotheses. A skewed population with 50 of the 60 subjects achieving scores indicative of sympathetic dominance occurred. Statistical comparison (t-tests) of the CAQ personality traits, and clinical factor scores of these 50 subjects labeled sympathetic dominant with CAQ norms for college students revealed means on five personality traits and three clinical factors were significantly different for the sympathetic dominant group at the .05 or greater level of significance. These findings were interpreted as limited support for Wenger's work and for the positions of Acker and Kagan that individuals with more reactive sympathetic nervous systems tend to have difficulty binding anxiety, poor emotional controls and outlets, ambivalence about interpersonal relationships, and a need for group acceptance.

The aim of this thesis is to provide insights into how previous negative social experiences and/or societal norms concerning body size influence social information processing. The first two studies included in this thesis were conducted in Germany, a society with high level of prejudice towards individuals with obesity. The third study was conducted in American Samoa, a society with low prejudice towards individuals with obesity. Study one (chapter 5.1) investigated potential alterations in social information processing and behavior in individuals with obesity compared to lean individuals by measuring heart rate and reaction times. To identify potential reasons for alterations in the individual’s personal history, the influence of weight-related teasing on social information processing was analyzed. In the second study (chapter 5.2), I examined how individuals with and without obesity respond to social inclusion and social exclusion by measuring affect and heart rate. Of special interest were subjective factors of body dissatisfaction and teasing experiences as potential influencing factors. Following this approach, the second study became a “travelling experiment” and was repeated in a Polynesian group on American Samoa (chapter 5.3), a country with a high obesity rate, but less negative social outcomes for individuals with obesity. It aimed at studying the influence of cultural norms and values related to body size as well as varying weight-related stigmatization on psychophysiological processing in social situations.:1 Introduction 2 Theoretical Background 2.1 Social exclusion and behavior 2.1.1 Evolutionary origins of social exclusion and stigmatization 2.1.2 Adaptive behavioral responses to recurrent negative social feedback 2.2 Social exclusion and affect 2.2.1 General biological aspects of emotions 2.2.2 Cultural aspects of emotions 2.2.3 Affect after social exclusion 2.3 Social exclusion and parasympathetic cardio-regulation 2.3.1 Parasympathetic cardio-regulation in psychological research 2.3.2 Parasympathetic cardio-regulation during negative social feedback 2.3.3 Methodological issues 2.4 Obesity in Western societies 2.4.1 Prevalence and health consequences 2.4.2 Obesity and parasympathetic cardio-regulation 2.4.3 The stigma of obesity 2.4.4 Obesity and social information processing 2.5 Obesity and the Samoan Islands 2.5.1 Geography and population 2.5.2 Traditional diets, modernization, and obesity prevalence 2.5.3 Cultural differences in the perception of body sizes 2.5.4 Body size perception in the Samoan Islands 2.5.5 Affect in Samoa 3 Rationale of the Experimental Work 4 Methods 4.1 Autonomic control of the heart 4.2 Heart rate variability analyses 5 Experimental Work 5.1 Study 1 – Differential heart rate responses to social and monetary reinforcement in women with obesity 5.2 Study 2 – Parasympathetic cardio-regulation during social interactions in individuals with obesity – The influence of negative body image 5.3 Study 3 – Body size-related socio-cultural norms in Westerners and Polynesians and their association with heart rate variability and affect during social interaction 5.3.1 Introduction 5.3.2 Methods 5.3.3 Results 5.3.4 Discussion 6 General Discussion and Implications 7 Summary 7.1 English summary 7.2 German summary 8 References 9 Appendix 9.1 Supplemental material 9.1.1 Participants: recruitment, inclusion and exclusion criteria 9.1.2 Overview procedures in Germany and American Samoa 9.1.3 Study 1 9.1.4 Study 2 9.1.5 Study 3 9.2 Declaration of authenticity 9.3 Authors' contributions 9.3.1 Study 1 9.3.2 Study 2 9.3.3 Study 3

Exaggerated cardiovascular reactivity and impaired recovery to psychological stress is independently related to cardiovascular disease (CVD), and may play a causal role in its development. I examined autonomic reactivity and recovery in 136 black, white, and Hispanic women who were predisposed to CVD, as indicated by a positive family history (FH+). Pre-ejection period (PEP; sympathetic) and respiratory sinus arrhythmia (RSA; parasympathetic) were measured during public speaking, mental arithmetic, and cold pressor tasks. Overall, FH+ participants exhibited greater RSA reactivity, while black participants exhibited impaired RSA recovery. These findings suggest that a hereditary predisposition for CVD is related to altered autonomic reactivity before any differences in resting levels are observed. Further, black participants did not exhibit a RSA rebound after the stress tasks, a key component in buffering the damaging effects of exaggerated sympathetic reactivity. These findings demonstrate the importance of examining parasympathetic activity in addition to sympathetic reactivity measures.

α2-Adrenergic receptor (AR) subtype mRNA (α2a, α2b, α2c) neuronal localization in human spinal cord has not been described. We therefore performed in situ hybridization to identify cell bodies at four levels of human spinal cord (cervical, thoracic, lumbar, sacral) containing α2AR subtype specific mRNA. α2AR mRNA is present in gray matter only (ventral > dorsal; sacral > cervical > thoracic = lumbar). In addition to α2AR mRNA in cell bodies in thoracic and lumbar intermediolateral (sympathetic) and sacral intermediate (parasympathetic) cell columns (lamina VII), all levels in dorsal horn laminae I, II, V, and ventral horn lamina IX, we demonstrate α2AR mRNA in dorsal horn laminae III and IV, and dorsal nucleus of Clarke, where α2ARs have not been described. Previously unreported heterogeneity in α2AR subtype distribution (α2a and α2bAR mRNA present, α2cAR mRNA virtually absent) is found at all sites of α2AR mRNA expression in human spinal cord, including locations known to mediate effects of α2AR agonist drugs on nociception, autonomic function and motor tone. Cervical spinal cord demonstrates a predominance of α2a mRNA signal, while thoracic, lumbar, and sacral spinal cord demonstrate an increasing predominance of α2bAR mRNA. If confirmed at a protein level, these findings have profound implications for therapeutic strategies in managing human pain.

The purpose of this study was to test the hypothesis that early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. After 2 wk of rapid ventricular pacing in nine anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs, and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine-sensitive, neuronally induced cardiac responses were also evaluated in eight sham-operated, unpaced animals. Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemosensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered α- or β-adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared with normal preparations. That dose failed to alter monitored cardiovascular indexes in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared with control, including decreased membrane resistance, indicative of reduced excitability. Early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine-sensitive, local-circuit neurons differentially remodel such that their capacity to influence cardiodynamics becomes obtunded.