RESUMEN
BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and despite obvious clinical importance remains its pathogenesis only partially explained. A relation between inflammation and AF has been suggested by findings of increased inflammatory markers in AF patients. OBJECTIVE: The goal of this study was to characterize morphologically and functionally CD45-positive inflammatory cell populations in atrial myocardium of patients with AF as compared to sinus rhythm (SR). METHODS: We examined 46 subjects (19 with AF, and 27 in SR) undergoing coronary bypass or valve surgery. Peroperative bioptic samples of the left and the right atrial tissue were examined using immunohistochemistry. RESULTS: The number of CD3+ T-lymphocytes and CD68-KP1+ cells were elevated in the left atrial myocardium of patients with AF compared to those in SR. Immune cell infiltration of LA was related to the rhythm, but not to age, body size, LA size, mitral regurgitation grade, type of surgery, systemic markers of inflammation or presence of diabetes or hypertension. Most of CD68-KP1+ cells corresponded to dendritic cell population based on their morphology and immunoreactivity for DC-SIGN. The numbers of mast cells and CD20+ B-lymphocytes did not differ between AF and SR patients. No foci of inflammation were detected in any sample. CONCLUSIONS: An immunohistochemical analysis of samples from patients undergoing open heart surgery showed moderate and site-specific increase of inflammatory cells in the atrial myocardium of patients with AF compared to those in SR, with prevailing population of monocyte-macrophage lineage. These cells and their cytokine products may play a role in atrial remodeling and AF persistence.
Asunto(s)
Arritmia Sinusal/patología , Fibrilación Atrial/patología , Atrios Cardíacos/patología , Miocardio/patología , Linfocitos T/patología , Anciano , Arritmia Sinusal/inmunología , Arritmia Sinusal/fisiopatología , Fibrilación Atrial/inmunología , Fibrilación Atrial/fisiopatología , Linfocitos B/inmunología , Linfocitos B/patología , Recuento de Células , Forma de la Célula , Femenino , Atrios Cardíacos/inmunología , Atrios Cardíacos/fisiopatología , Humanos , Masculino , Mastocitos/inmunología , Mastocitos/patología , Persona de Mediana Edad , Miocardio/inmunología , Linfocitos T/inmunologíaRESUMEN
Congenital heart block (CHB) is a conduction abnormality characterized by complete atrioventricular (AV) block. CHB affects fetuses and/or newborn of mothers with autoantibodies reactive with ribonucleoproteins 48-kDa SSB/La, 52-kDa SSA/Ro, and 60-kDa SSA/Ro. We recently established animal models of CHB and reported, for the first time, significant sinus bradycardia preceding AV block. This unexpected observation implies that the spectrum of conduction abnormalities extends beyond the AV node to also affect the SA node. To test this hypothesis, we investigated the functional basis of this sinus bradycardia by characterizing the effects of antibodies from mothers with CHB children (positive IgG) on ionic currents that are known to significantly contribute to spontaneous pacing in SA node cells. We recorded L- (I(Ca.L)) and T- (I(Ca.T)) type Ca2+, delayed rectifier K+ (I(K)), hyperpolarization-activated (I(f)) currents, and action potentials (APs) from young rabbit SA node cells. We demonstrated that positive IgG significantly inhibited both I(Ca.T) and I(Ca.L) and induced sinus bradycardia but did not affect I(f) and I(K). Normal IgG from mothers with healthy children did not affect all the currents studied and APs. These results establish that IgG from mothers with CHB children causes substantial inhibition of I(Ca.T) and I(Ca.L), two important pacemaker currents in rabbit SA node cells and point to both I(Ca.T) and I(Ca.L) as major players in the ionic mechanism by which maternal antibodies induce sinus bradycardia in CHB. These novel findings have important clinical significance and suggest that sinus bradycardia may be a potential marker in the detection and prevention of CHB. The full text of this article is available online at http://circres.ahajournals.org
Asunto(s)
Anticuerpos Antinucleares/farmacología , Arritmia Sinusal/fisiopatología , Autoantígenos , Bradicardia/fisiopatología , Bloqueo Cardíaco/fisiopatología , Inmunoglobulina G/farmacología , ARN Citoplasmático Pequeño , Nodo Sinoatrial/fisiopatología , Potenciales de Acción , Adulto , Animales , Anticuerpos Antinucleares/inmunología , Arritmia Sinusal/etiología , Arritmia Sinusal/inmunología , Bradicardia/etiología , Bradicardia/inmunología , Calcio/metabolismo , Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo L/fisiología , Canales de Calcio Tipo T/efectos de los fármacos , Canales de Calcio Tipo T/fisiología , Femenino , Bloqueo Cardíaco/complicaciones , Bloqueo Cardíaco/congénito , Bloqueo Cardíaco/inmunología , Humanos , Inmunidad Materno-Adquirida , Inmunoglobulina G/inmunología , Transporte Iónico/efectos de los fármacos , Embarazo , Conejos , Ribonucleoproteínas/inmunología , Nodo Sinoatrial/patología , Antígeno SS-BRESUMEN
BACKGROUND: The relationship between anti-beta-adrenergic (anti-betaR) and anti-M(2)-cholinergic (anti-M2R) receptor antibodies (Abs) and cardiac arrhythmias and their biochemical effects have not been systematically investigated. METHODS AND RESULTS: We studied 41 patients, 28 with ventricular arrhythmias (primary or due to Chagas' heart disease or idiopathic dilated cardiomyopathy; group I), 13 with sinus node dysfunction (primary or caused by Chagas' heart disease; group II), and 10 healthy controls (group III). The chronotropic effects of the IgG and immunopurified anti-beta(1)RAbs or anti-M2RAbs were assessed on cultured cardiomyocytes before and after exposure to atropine and propranolol. The biochemical effects of the IgG from 9 patients from group I, 6 from group II, and 6 controls were evaluated on COS7 cells transfected with genes encoding for beta(1),beta(2)-adrenergic receptors (cAMP increment) or M(2)-cholinergic receptors (phosphatidylinositol increment). The IgG from group I patients exerted a positive chronotropic action, with a high prevalence of anti-betaRAbs (75%) and low prevalence of anti-M2RAbs (10.7%) and induced a clear-cut and long-lasting increment in cAMP. The IgG from group II patients depressed chronotropism, with a high prevalence of anti-M2RAbs (76.9%) and low prevalence of anti-betaRAbs (15.4%) and evoked a marked augmentation of phosphatidylinositol. CONCLUSIONS: Our results demonstrate a strong correlation between anti-betaRAbs and ventricular arrhythmias and anti-M2RAbs and sinus node dysfunction. Anti-betaRAbs increase and anti-M2RAbs inhibit cAMP production. These findings offer new insight into the etiology and pathophysiology of cardiac arrhythmias, with therapeutic implications.
Asunto(s)
Arritmia Sinusal/inmunología , Arritmias Cardíacas/inmunología , Autoanticuerpos/inmunología , Receptores Adrenérgicos beta/inmunología , Receptores Colinérgicos/inmunología , Adulto , Anciano , Secuencia de Aminoácidos , Animales , Arritmia Sinusal/complicaciones , Arritmias Cardíacas/complicaciones , Atropina/farmacología , Autoanticuerpos/análisis , Células COS , Cardiomiopatía Dilatada/complicaciones , Cardiomiopatía Dilatada/inmunología , Cardiomiopatía Chagásica/complicaciones , Cardiomiopatía Chagásica/inmunología , AMP Cíclico/metabolismo , Electrocardiografía , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Fosfatidilinositoles/metabolismo , Propranolol/farmacología , Receptores Adrenérgicos beta/química , Receptores Adrenérgicos beta/genética , Receptores Colinérgicos/química , Receptores Colinérgicos/genética , Sistemas de Mensajero Secundario/efectos de los fármacosRESUMEN
The autonomic nervous system modulates gastrointestinal motility, secretion and mucosal immunity. Its dysfunction may be of pathogenetic importance in inflammatory bowel disease (IBD). This study aimed at investigating the autonomic nervous function in patients with IBD. Forty-seven patients with IBD, 28 with Crohn's disease (CD) and 19 with ulcerative colitis (UC), were investigated by means of 5 cardiovascular and 2 pupillary standardized autonomic nervous function tests. In CD and UC, cardiovascular autonomic neuropathy was very rare (0%, 5%), whereas pupillary autonomic neuropathy was more prevalent (21%, 21%). In contrast to autonomic neuropathy, overall cardiovascular (CD: 29%, UC: 26%) and pupillary autonomic hyperreflexia (46%, 37%) were found more often. Patients with CD and UC demonstrated elevated percentiles in the respiratory sinus arrhythmia test as compared to controls (RSA: 82.3 +/- 3.9%, 80.0 +/- 5.9%, controls: 50.0% +/- 1.5%, p < 0.0001). CD patients with, as compared to patients without, RSA hyperreflexia had significantly higher CDAIs (p < 0.001), increased erythrocyte sedimentation rates (p < 0.005) and more often extraintestinal disease manifestations (p < 0.001). UC patients with, as compared to patients without, pupillary latency time hyperreflexia had lower hemoglobin (p < 0.05), lower albumin (p < 0.01) and increased erythrocyte sedimentation rates (p < 0.05). Autonomic hyperreflexia was significantly associated with more severe inflammation and systemic disease in IBD. Hyperreflexia may be a response to inflammation or a pathogenetic element that drives mucosal inflammation.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/inmunología , Colitis Ulcerosa/fisiopatología , Enfermedad de Crohn/fisiopatología , Reflejo Anormal/inmunología , Adolescente , Adulto , Anciano , Arritmia Sinusal/inmunología , Arritmia Sinusal/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/inmunología , Enfermedades Cardiovasculares/fisiopatología , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/inmunología , Femenino , Humanos , Inflamación/epidemiología , Inflamación/inmunología , Inflamación/fisiopatología , Masculino , Persona de Mediana Edad , Prevalencia , Tiempo de Reacción/inmunología , Respiración , Factores de TiempoRESUMEN
The authors describe 6 cases of pregnancy, four of the patients presenting fetomaternal Rhesus incompatibility, and two showing no abnormality. Fetal heart rhythm (FHR) recordings in all patients demonstrated the presence of a sinusoidal rhythm, either alone or associated with deceleration. The physiopathology of the rhythm, according to a very critical analysis of reports in the published literature (very severe fetal anemia, hypoxia), was not typical in three of the cases. The authors conclude that the observation of this sinusoidal rhythm for a period of up to 60 min, but not repeated, does not constitute a danger for the fetus. If the period is longer, however, or if there is a fetomaternal pathological condition, decelerations, or reduced amplitude of FHR oscillations, there is a very severe risk to the fetus and the need for urgent delivery has to be seriously considered.