No description available.

Familial amyloidosis with polyneuropathy (FAP) is a neuropathic form of heredofamilial systemic amyloidosis. Clusters of patients have been reported predominantly from Portugal, Japan and Sweden. The present study examines the involvement of the heart in individuals with the Swedish variety of FAP. During long-term ECG recording in 16 patients, a high frequency of disturbances of sinus node function and atrioventricular conduction were observed. Long-term ECG may help considerably in the evaluation of symptoms attributable to disturbances of heart rhythm in FAP. A retrospective survey of 20 patients with FAP treated with a pacemaker showed that the indication for pacing was advanced atrioventricular block (12 cases), dysfunction of the sinus node (5 cases), and atrial fibrillation with a slow ventricular response (3 cases). All patients experienced the effective relief of symptoms attributable to a slow ventricular rate. The long-term prognosis, however, seemed unaffected by this treatment. Histopathological examination of the sinoatrial (9 cases) and atrioventricular (6 cases) parts of the conduction system showed marked amyloid infiltration in all cases, which may explain the high occurrence of disturbances of cardiac rhythm and conduction. Twelve patients were examined by two-dimensional echocardiography and changes of varying degrees, such as highly refractile myocardial echoes (12 cases) and thickened ventricular walls (8 cases) and valves (7 cases), could be observed. Technetium-99m-pyrophosphate scintigraphy of the same patients revealed abnormal myocardial uptake of the isotope only in four. Echocardiography thus seems to be superior to scintigraphy for non-invasive detection of cardiac involvement in FAP. Myocardial samples from regions producing highly refractile myocardial echoes were obtained at in vitro échocardiographie examination of hearts from FAP autopsy cases. Histological examination showed that the highly refractile echoes corresponded to more or less sharply delineated nodules, containing amyloid and collagen in various amounts. / digitalisering@umu

A eletrocardiografia dinâmica ambulatorial (EDA) sistema Holter, permite o registro contínuo da atividade elétrica cardíaca em um paciente, durante sua atividade diária normal. Arritmias cardíacas ocorrem em indivíduos da espécie felina, mas pouco se conhece a respeito destas alterações em Gatos Maine Coon (GMC). O objetivo deste estudo foi baseado na avaliação da frequência e do ritmo cardíacos, como também, na presença de arritmias cardíacas em GMC, por meio da EDA sistema Holter. Foram avaliados 23 (vinte e três) gatos Maine Coon, sendo nove machos e 14 fêmeas, com idade compreendida entre seis e 82 meses (39 ± 21 meses), e peso corpóreo entre 3,7 e 8 kg (5,4 ± 1,4 kg). Para confirmar ou excluir o diagnóstico de cardiomiopatia hipertrófica (CMH), todos os animais foram avaliados por meio de ecocardiografia convencional. Posteriormente, foram fenotipicamente classificados em: não acometidos pela CMH (n=20) e acometidos pela CMH (n=3). A monitorização Holter foi realizada com o aparelho digital modelo 300-9 MINI, da DMS®, fixado diretamente ao dorso do animal, com bandagem elástica auto-adesiva (Coban, 3M®) e esparadrapo, permitindo liberdade de movimento aos mesmos. Analisou-se, em média, 1.346 ± 84,7 minutos, com um total de 220.878 ± 31.457,4 complexos QRS. Considerando-se todos os exames, a frequência cardíaca (FC) variou de 58 a 254 bpm, com média de FC média de 164,2 ± 22,02 bpm (variando de 108 a 205 bpm), sendo que a FC mínima apresentou média de 89,9 ± 14,7 bpm (variando de 58 a 131 bpm) e a FC máxima de 250,9 ± 6,02 bpm (variando de 231 a 254 bpm). Fêmeas Maine Coon não acometidas pela CMH apresentaram média de FC média superior à dos machos (p=0,03), que também não eram portadores da afecção. As frequências cardíacas, mínima, média e máxima de GMC, variaram com o período do dia (p ≤ 0,001). O ritmo sinusal foi predominante em todos os GMC avaliados. A presença de bloqueio de ramo direito incompleto em GMC mais velhos, foi superior à encontrada em GMC mais jovens (p=0,026). Apenas dois animais apresentaram episódios de bloqueio fascicular anterior esquerdo. Arritmias atriais e ventriculares isoladas, aos pares, como também, episódios de taquicardia atrial e ventricular não sustentadas, foram detectadas no Holter dos GMC avaliados. A presença de complexos atriais prematuros isolados apenas nas fêmeas, resultou em diferença estatística entre os sexos (p=0,048). Conclui-se que o exame é de fácil execução em GMC, que após período mínimo de adaptação, toleram bem a presença do gravador. / Dynamic ambulatory electrocardiography (DAE) - Holter system, allows the continuous recording of cardiac electrical activity in a patient during its normal daily activity. Cardiac arrhythmias occur in individuals of feline species, but little is known about these alterations in Maine Coon cats (MCC). The aim of this study was based on the evaluation of heart rate and rhythm, as well as in the presence of cardiac arrhythmias in MCC, by EDA - Holter system. 23 (twenty three) Maine Coon cats were evaluated, being nine males and 14 females, aged between six and 82 months (39 ± 21 months), and body weight between 3.7 and 8 kg (5.4 ± 1.4 kg). To confirm or exclude hypertrophic cardiomyopathy (HCM) diagnosis, all animals were examined with conventional echocardiography. Then, were phenotypically classified in: not affected by HCM (n=20) and affected by HCM (n=3). Holter monitoring was performed with digital device MINI model 300-9, DMS®, directly attached to the back of the animal, with self-adhesive elastic bandage (Coban, 3M®) and adhesive tape, allowing them free movement. On average, 1.346 ± 84.7 minutes were analyzed. All together, the cats had an average of 220.878 ± 31.457,4 heart beats, during the record period, with heart rates ranged from 58 to 254 bpm. Average heart rates were 164,2 ± 22,02 bpm (ranging from 108 to 205 bpm), the mean minimum heart rate was 89,9 ± 14,7 bpm (ranging from 58 to 131 bpm) and the mean maximum heart rate of 250,9 ± 6,02 bpm (ranging from 231 to 254 bpm). Maine Coon females not affected by HCM presented average higher than the average heart rate of males (p=0.03), which also did not carry the disease. Mean, minimum and maximum heart rates of MCC ranged with the time of day (p ≤ 0.001). Sinus rhythm was predominant in all MCC reviews. The presence of incomplete right bundle branch block in older MCC was higher than that found in younger MCC (p=0.026). Only two animals presented episodes of left anterior fascicular block. Isolated atrial and ventricular arrhythmias, in pairs, as well as episodes of non sustained atrial and ventricular tachycardia, were detected on Holter reviews of MCC. The presence of isolated premature atrial complexes only in females, resulted in statistical difference between genders (p=0.048). Therefore, the conclusion is that dynamic ambulatory electrocardiography can be readly obtained in MCC, that after a minimum period of adjustment, remarkably tolerate the presence of the recorder.

A significância clínica dos achados eletrocardiográficos para pacientes sem histórico de doença cardiovascular é pequeno ou inexistente, porém em pacientes com doenças cardiovasculares poderia justificar o uso de monitoração contínua, incluindo o uso de eletrocardiograma além de terapêutica comportamental ou medicamentosa para certos procedimentos odontológicos com níveis de estresse moderado a elevado. Este estudo teve como objetivo a avaliação das alterações eletrocardiográficas em cirurgias para a colocação de implantes dentários sob anestesia local com cloridrato de lidocaína 2% associado a epinefrina, com uso de pré-medicação ansiolítica com 15mg de midazolam. O estudo foi realizado em 15 pacientes ASA I, com necessidade de implantes dentários, bilaterais em mandíbula. O estudo foi comparativo com placebo administrado aleatoriamente, duplo cego 1 hora antes ao procedimento. O eletrocardiograma registrou 12 derivações estáticas a cada 2 minutos e o registro da derivação D2 de maneira contínua, avaliando o comportamento morfológico da onda eletrocardiográfica e a presença de arritmias durante o experimento. Não foram encontradas diferenças significantes entre os grupos estudados. Quando comparamos o comportamento dos parâmetros eletrocardiográficos durante as fases do procedimento, observamos diferenças estatística (p<0,01) para a freqüência cardíaca, amplitude da onda P e duração dos intervalos RR e QTc para o grupo com sedação. Foram observadas arritmias em 53,3% dos pacientes. As arritmias encontradas foram a taquicardia e a bradicardia sinusal, as extrasístoles supraventriculares, ventriculares e extrasístole atrial bloqueada, em ambos os grupos de maneira semelhante, com maior incidência nas fases inicio e perfuração. As arritmias encontradas foram consideradas de baixo risco para pacientes sem compromeitmento sistêmico. Concluiu-se que o uso de 15mg de midazolam não apresentou diferença quando comparado ao placebo. A fase incisão apresentou maiores valores de freqüência cardíaca e amplitude da onda P e menores para duração dos intervalos RR e QTc. As arritmias mais frequentes foram as extra-sístoles e a taquicardias sinusais. / The clinical significance of eletrocardiographic evalution in patients without cardiovascular disease is very small. However, continuous monitoring using electrocardiogram and anxiety control methods, such as behaviour manegement technique and premedication, may be justified in patients with cardiovascular disease undergoing dental procedures that cause stress. The aim of this study was to evaluate the electrocardiographic alterations that occur during oral implant surgeries under local anesthesia with a 2% lidocaine hydrochloride,1: 100,000 epinephrine and midazolam sedation. One hour prior to surgery, patients were given premedication (15 mg midazolam or placebo). The subjects of this study were 15 ASA I patients, who needed bilateral implant surgery on the lower jaw. A total of 30 implant surgeries were evaluated in a double blind study. Electrocardiographic tracing the 12 static leads every two minutes and Lead II was registered in a continuous manner during sugery. Automatic measurement of the following electrocardiographic parameters were also performed: heart rate (HR), duration and amplitude of P wave, ST segment depression, duration of PR segment, QRS complex, and duration of RR, QT and QTc intervals. No statistically significant differences were found between the groups, midazolam and placebo. Howerver, analysis of the data at different stages of implant surgery showed significant difference at 1% level in relation to heart rate and, amplitude of P wave, duration of RR and QTc intervals in the midazolam group. Cardiac arrhythmias were found in 53,3% of the patients. The following cardiac arrhythmias were detected: sinusal tachycardia and bradycardia, sinusal arrhythmia, supraventricular extrasystole, ventricular extrasystole, and blocked atrial extrasystole. Arrhythmias occurred, most frequently, at the begining of implant surgery and during drilling, in a similar pattern in both groups. The arrhythmias detected in these patients were considered low risk factors in patients with no systemic alterations. In conclusion, the use of 15 mg of midazolam seemed to be no different from placebo in this study. During incision, we observed the highest heart rate values and amplitude of P wave and the lowest RR and QTc intervals. Extrasystole and sinusal tachycardia were the most frequent arrhythmias detected in these patients.

Arrhythmias are often caused by aberrant ion channel activity, resulting in remodeling of the cardiac action potential. Two K + currents, IKs and IKr, contribute to phase III repolarization of the human cardiac action potential. Human ether-a-go-go-related gene 1 (hERG1), a voltage-gated potassium channel, underlies IKr. Alterations in the repolarization phase of the action potential, and in particular IKr, can lead to arrhythmias, long or short QT syndrome, heart disease, and sudden cardiac death. HERG1A has two putative N-glycosylation sites located in the S5-S6 linker region, one of which is N-glycosylated. The aim of the first study was to determine whether and how N-linked glycosylation modifies hERG1A channel function. Voltage-dependent gating and kinetics of hERG1A were evaluated under conditions of full glycosylation, no sialylation, in the absence of complex N-glycans, and following the removal of the full N-glycosylation structure. The hERG1A steady state activation relationship was shifted linearly along the voltage axis by a depolarizing ~9 mV under each condition of reduced glycosylation. Steady state channel availability curves were shifted by a much greater depolarizing 20–30 mV under conditions of reduced glycosylation. There was no significant difference in steady state gating parameters among the less glycosylated channels, suggesting that channel sialic acids are responsible for most of the effect of N-glycans on hERG1A gating. A large rightward shift in hERG1A window current for the less glycosylated channels was caused by the observed depolarizing shifts in steady state activation and inactivation. The much larger shift in inactivation compared to activation leads to an increase in hERG1A window current. Together, these data suggest that there is an increase in the persistent hERG current that occurs at more depolarized potentials under conditions of reduced glycosylation. This would lead to increased hERG1A activity during the AP, effectively increasing the rate of repolarization, and reducing AP duration, as observed through in silico modeling of the ventricular AP. The data describe a novel mechanism by which hERG1A activity is modulated by physiological and pathological changes in hERG1A glycosylation, with increased channel sialylation causing a loss of hERG1A activity that would likely cause an extension of the ventricular AP. The second study was to evaluate possible changes in antibiotic drug block as a result of alterations to N-glycosylation. We determined that N-glycans play a protective role on the hERG1A channel. SMX, Erythromycin, and Penicillin G were assessed individually at three concentrations. The data showed increases in antibiotic block with decreases in N-glycans. In addition, alterations in the voltage-dependence of block with changes in N-glycans were observed. SMX block was voltage-independent at each drug concentration under conditions of reduced sialylation only. Overall, these data indicate a functional role for N-glycosylation in the modulation of hERG1A antibiotic block, suggesting that even small changes in channel N-glycosylation modulate hERG1A block, and thereby likely impact the rate of action potential repolarization. The data from these studies enhances our understanding of the role of N-glycosylation on hERG1A function and drug block, and how that role will impact the cardiac action potential and overall cardiac excitability.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 4 uppsatser.

The phytocannabinoid cannabidiol (CBD) has a complex pharmacology which is thought to include, but is not limited to, an ability to act as an inverse agonist at the CB1 and CB2 receptors and an antagonist of GPR55. Moreover, is has been shown to reduce infarct size and ameliorate reductions in left ventricular function in vivo. These improvements in the pathogenesis of experimental MI are accompanied by a reduction in inflammatory cell migration to the area at risk. More recently it has been shown that CBD is anti-arrhythmic in acute experimental MI. Thus, it was suggested that the cardioprotective effects of CBD might be due to an anti-inflammatory action. In addition, GPR55 receptor activation is acknowledged to mediate mobilisation of intracellular Ca2+ (Ca2+i) which could potentially be pro-arrhythmic and so CBD, as an antagonist may confer cardioprotection via GPR55. However, the receptors and/or mechanisms responsible for mediating the cardioprotective effects of CBD are get to be determined. The present studies were therefore performed to; (1) better understand the pharmacology of CBD by assessing haemodynamic responses to CBD and other cannabinoids ligands in anaesthetised rats, (2) investigate the receptors involved in the anti-arrhythmic effect of CBD in a rat model of coronary artery occlusion (CAO), and (3) investigate if CBD can alter [Ca2+]i in isolated rat cardiomyocytes. The characterisation of the pharmacology of CBD in vivo showed that; firstly, CB1 receptor activation causes a hypotensive response which can be dose-dependently inhibited by AM251; secondly, both CBD and AM251 alone (a CB1 receptor antagonist and GPR55 agonist) can induce vasodepressor responses and finally, CBD can potentiate the AM251-mediated hypotension when co-administered, suggesting possible cross-talk between the CB1 and GPR55. Results from CAO studies showed that CBD and AM251 each have the capacity to reduce arrhythmias. Moreover, when CBD and AM251 were co-administered the anti-arrhythmic capacity of either alone was potentiated. However, the degree of potentiation was dependent on the order of administration, suggesting that more than one receptor is involved in the summative anti-arrhythmic effects. The investigation of cardiomyocyte [Ca2+]i suggested that AM251 can modulate [Ca2+]i at the level of the cardiomyocyte, while CBD cannot. These data give novel insight into the anti-arrhythmic effects of CBD and, moreover, for the first time demonstrate that AM251 is anti-arrhythmic. In addition, these data suggest a role for GPR55 in increasing [Ca2+]i via AM251.

A significância clínica dos achados eletrocardiográficos para pacientes sem histórico de doença cardiovascular é pequeno ou inexistente, porém em pacientes com doenças cardiovasculares poderia justificar o uso de monitoração contínua, incluindo o uso de eletrocardiograma além de terapêutica comportamental ou medicamentosa para certos procedimentos odontológicos com níveis de estresse moderado a elevado. Este estudo teve como objetivo a avaliação das alterações eletrocardiográficas em cirurgias para a colocação de implantes dentários sob anestesia local com cloridrato de lidocaína 2% associado a epinefrina, com uso de pré-medicação ansiolítica com 15mg de midazolam. O estudo foi realizado em 15 pacientes ASA I, com necessidade de implantes dentários, bilaterais em mandíbula. O estudo foi comparativo com placebo administrado aleatoriamente, duplo cego 1 hora antes ao procedimento. O eletrocardiograma registrou 12 derivações estáticas a cada 2 minutos e o registro da derivação D2 de maneira contínua, avaliando o comportamento morfológico da onda eletrocardiográfica e a presença de arritmias durante o experimento. Não foram encontradas diferenças significantes entre os grupos estudados. Quando comparamos o comportamento dos parâmetros eletrocardiográficos durante as fases do procedimento, observamos diferenças estatística (p<0,01) para a freqüência cardíaca, amplitude da onda P e duração dos intervalos RR e QTc para o grupo com sedação. Foram observadas arritmias em 53,3% dos pacientes. As arritmias encontradas foram a taquicardia e a bradicardia sinusal, as extrasístoles supraventriculares, ventriculares e extrasístole atrial bloqueada, em ambos os grupos de maneira semelhante, com maior incidência nas fases inicio e perfuração. As arritmias encontradas foram consideradas de baixo risco para pacientes sem compromeitmento sistêmico. Concluiu-se que o uso de 15mg de midazolam não apresentou diferença quando comparado ao placebo. A fase incisão apresentou maiores valores de freqüência cardíaca e amplitude da onda P e menores para duração dos intervalos RR e QTc. As arritmias mais frequentes foram as extra-sístoles e a taquicardias sinusais. / The clinical significance of eletrocardiographic evalution in patients without cardiovascular disease is very small. However, continuous monitoring using electrocardiogram and anxiety control methods, such as behaviour manegement technique and premedication, may be justified in patients with cardiovascular disease undergoing dental procedures that cause stress. The aim of this study was to evaluate the electrocardiographic alterations that occur during oral implant surgeries under local anesthesia with a 2% lidocaine hydrochloride,1: 100,000 epinephrine and midazolam sedation. One hour prior to surgery, patients were given premedication (15 mg midazolam or placebo). The subjects of this study were 15 ASA I patients, who needed bilateral implant surgery on the lower jaw. A total of 30 implant surgeries were evaluated in a double blind study. Electrocardiographic tracing the 12 static leads every two minutes and Lead II was registered in a continuous manner during sugery. Automatic measurement of the following electrocardiographic parameters were also performed: heart rate (HR), duration and amplitude of P wave, ST segment depression, duration of PR segment, QRS complex, and duration of RR, QT and QTc intervals. No statistically significant differences were found between the groups, midazolam and placebo. Howerver, analysis of the data at different stages of implant surgery showed significant difference at 1% level in relation to heart rate and, amplitude of P wave, duration of RR and QTc intervals in the midazolam group. Cardiac arrhythmias were found in 53,3% of the patients. The following cardiac arrhythmias were detected: sinusal tachycardia and bradycardia, sinusal arrhythmia, supraventricular extrasystole, ventricular extrasystole, and blocked atrial extrasystole. Arrhythmias occurred, most frequently, at the begining of implant surgery and during drilling, in a similar pattern in both groups. The arrhythmias detected in these patients were considered low risk factors in patients with no systemic alterations. In conclusion, the use of 15 mg of midazolam seemed to be no different from placebo in this study. During incision, we observed the highest heart rate values and amplitude of P wave and the lowest RR and QTc intervals. Extrasystole and sinusal tachycardia were the most frequent arrhythmias detected in these patients.

A eletrocardiografia dinâmica ambulatorial (EDA) sistema Holter, permite o registro contínuo da atividade elétrica cardíaca em um paciente, durante sua atividade diária normal. Arritmias cardíacas ocorrem em indivíduos da espécie felina, mas pouco se conhece a respeito destas alterações em Gatos Maine Coon (GMC). O objetivo deste estudo foi baseado na avaliação da frequência e do ritmo cardíacos, como também, na presença de arritmias cardíacas em GMC, por meio da EDA sistema Holter. Foram avaliados 23 (vinte e três) gatos Maine Coon, sendo nove machos e 14 fêmeas, com idade compreendida entre seis e 82 meses (39 ± 21 meses), e peso corpóreo entre 3,7 e 8 kg (5,4 ± 1,4 kg). Para confirmar ou excluir o diagnóstico de cardiomiopatia hipertrófica (CMH), todos os animais foram avaliados por meio de ecocardiografia convencional. Posteriormente, foram fenotipicamente classificados em: não acometidos pela CMH (n=20) e acometidos pela CMH (n=3). A monitorização Holter foi realizada com o aparelho digital modelo 300-9 MINI, da DMS®, fixado diretamente ao dorso do animal, com bandagem elástica auto-adesiva (Coban, 3M®) e esparadrapo, permitindo liberdade de movimento aos mesmos. Analisou-se, em média, 1.346 ± 84,7 minutos, com um total de 220.878 ± 31.457,4 complexos QRS. Considerando-se todos os exames, a frequência cardíaca (FC) variou de 58 a 254 bpm, com média de FC média de 164,2 ± 22,02 bpm (variando de 108 a 205 bpm), sendo que a FC mínima apresentou média de 89,9 ± 14,7 bpm (variando de 58 a 131 bpm) e a FC máxima de 250,9 ± 6,02 bpm (variando de 231 a 254 bpm). Fêmeas Maine Coon não acometidas pela CMH apresentaram média de FC média superior à dos machos (p=0,03), que também não eram portadores da afecção. As frequências cardíacas, mínima, média e máxima de GMC, variaram com o período do dia (p &le; 0,001). O ritmo sinusal foi predominante em todos os GMC avaliados. A presença de bloqueio de ramo direito incompleto em GMC mais velhos, foi superior à encontrada em GMC mais jovens (p=0,026). Apenas dois animais apresentaram episódios de bloqueio fascicular anterior esquerdo. Arritmias atriais e ventriculares isoladas, aos pares, como também, episódios de taquicardia atrial e ventricular não sustentadas, foram detectadas no Holter dos GMC avaliados. A presença de complexos atriais prematuros isolados apenas nas fêmeas, resultou em diferença estatística entre os sexos (p=0,048). Conclui-se que o exame é de fácil execução em GMC, que após período mínimo de adaptação, toleram bem a presença do gravador. / Dynamic ambulatory electrocardiography (DAE) - Holter system, allows the continuous recording of cardiac electrical activity in a patient during its normal daily activity. Cardiac arrhythmias occur in individuals of feline species, but little is known about these alterations in Maine Coon cats (MCC). The aim of this study was based on the evaluation of heart rate and rhythm, as well as in the presence of cardiac arrhythmias in MCC, by EDA - Holter system. 23 (twenty three) Maine Coon cats were evaluated, being nine males and 14 females, aged between six and 82 months (39 ± 21 months), and body weight between 3.7 and 8 kg (5.4 ± 1.4 kg). To confirm or exclude hypertrophic cardiomyopathy (HCM) diagnosis, all animals were examined with conventional echocardiography. Then, were phenotypically classified in: not affected by HCM (n=20) and affected by HCM (n=3). Holter monitoring was performed with digital device MINI model 300-9, DMS®, directly attached to the back of the animal, with self-adhesive elastic bandage (Coban, 3M®) and adhesive tape, allowing them free movement. On average, 1.346 ± 84.7 minutes were analyzed. All together, the cats had an average of 220.878 ± 31.457,4 heart beats, during the record period, with heart rates ranged from 58 to 254 bpm. Average heart rates were 164,2 ± 22,02 bpm (ranging from 108 to 205 bpm), the mean minimum heart rate was 89,9 ± 14,7 bpm (ranging from 58 to 131 bpm) and the mean maximum heart rate of 250,9 ± 6,02 bpm (ranging from 231 to 254 bpm). Maine Coon females not affected by HCM presented average higher than the average heart rate of males (p=0.03), which also did not carry the disease. Mean, minimum and maximum heart rates of MCC ranged with the time of day (p &le; 0.001). Sinus rhythm was predominant in all MCC reviews. The presence of incomplete right bundle branch block in older MCC was higher than that found in younger MCC (p=0.026). Only two animals presented episodes of left anterior fascicular block. Isolated atrial and ventricular arrhythmias, in pairs, as well as episodes of non sustained atrial and ventricular tachycardia, were detected on Holter reviews of MCC. The presence of isolated premature atrial complexes only in females, resulted in statistical difference between genders (p=0.048). Therefore, the conclusion is that dynamic ambulatory electrocardiography can be readly obtained in MCC, that after a minimum period of adjustment, remarkably tolerate the presence of the recorder.

BACKGROUND: Neuronal remodeling in human heart disease is not well understood. METHODS: Stellate ganglia from patients with cardiomyopathy (CMY) and refractory ventricular arrhythmias undergoing cardiac sympathetic denervation (n = 8), and from organ donors with normal hearts (n = 8) collected at the time of organ procurement were compared. Clinical data on all subjects were reviewed. Electron microscopy (EM), histologic, and immunohistochemical assessments of neurotransmitter profiles, glial activation and distribution, and lipofuscin deposition, a marker of oxidative stress, were quantified. RESULTS: In CMY specimens, lipofuscin deposits were larger, and present in more neurons (26.3% ± 6.3% vs. 16.7% ± 7.6%, P < 0.043), than age-matched controls. EM analysis revealed extensive mitochondrial degeneration in CMY specimens. T cell (CD3+) infiltration was identified in 60% of the CMY samples, with one case having large inflammatory nodules, while none were identified in controls. Myeloperoxidase-immunoreactive neutrophils were also identified at parenchymal sites distinct from inflammatory foci in CMY ganglia, but not in controls. The adrenergic phenotype of pathologic samples revealed a decrease in tyrosine hydroxylase staining intensity compared with controls. Evaluation of cholinergic phenotype by staining for the vesicular acetylcholine transporter revealed a low but comparable number of cholinergic neurons in ganglia from both groups and demonstrated that preganglionic cholinergic innervation was maintained in CMY ganglia. S100 staining (a glial cell marker) demonstrated no differences in glial distribution and relationship to neurons; however, glial activation demonstrated by glial fibrillary acidic protein (GFAP) staining was substantially increased in pathologic specimens compared with controls. CONCLUSIONS: Stellate ganglia from patients with CMY and arrhythmias demonstrate inflammation, neurochemical remodeling, oxidative stress, and satellite glial cell activation. These changes likely contribute to excessive and dysfunctional efferent sympathetic tone, and provide a rationale for sympathectomy as a treatment for arrhythmias in this population. FUNDING: This work was made possible by support from NIH grants HL125730 to OAA, GM107949 to DBH, and HL084261 and OT2OD023848 to KS.