RESUMO
INTRODUCTION: Parasympathetic dysfunction may play a role in the genesis of arrhythmias in Chagas disease. AIM: This study evaluates the acute effects of pyridostigmine (PYR), a reversible cholinesterase inhibitor, on the occurrence of arrhythmias in patients with Chagas cardiac disease. METHOD: Following a double-blind, randomized, placebo-controlled, cross-over protocol, 17 patients (age 50±2 years) with Chagas cardiac disease type B underwent 24-hour Holter recordings after oral administration of either pyridostigmine bromide (45 mg, 3 times/day) or placebo (PLA). RESULTS: Pyridostigmine reduced the 24-hours incidence (median [25%-75%]) of premature ventricular beats-PLA: 2998 (1920-4870), PYR: 2359 (940-3253), P=.044; ventricular couplets-PLA: 84 (15-159), PYR: 33 (6-94), P=.046. Although the total number of nonsustained ventricular tachycardia in the entire group was not different (P=.19) between PLA (1 [0-8]) and PYR (0 [0-4]), there were fewer episodes under PYR in 72% of the patients presenting this type of arrhythmia (P=.033). CONCLUSION: Acute administration of pyridostigmine reduced the incidence of nonsustained ventricular arrhythmias in patients with Chagas cardiac disease. Further studies that address the use of pyridostigmine by patients with Chagas cardiac disease under a more prolonged follow-up are warranted.
Assuntos
Antiarrítmicos/administração & dosagem , Cardiomiopatia Chagásica/tratamento farmacológico , Inibidores da Colinesterase/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Brometo de Piridostigmina/administração & dosagem , Taquicardia Ventricular/prevenção & controle , Complexos Ventriculares Prematuros/prevenção & controle , Administração Oral , Antiarrítmicos/efeitos adversos , Doenças Assintomáticas , Brasil , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/parasitologia , Inibidores da Colinesterase/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Esquema de Medicação , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Brometo de Piridostigmina/efeitos adversos , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/parasitologia , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/parasitologia , Complexos Ventriculares Prematuros/fisiopatologiaRESUMO
OBJECTIVE: Parasympathetic dysfunction is an independent risk factor in individuals with coronary artery disease, and cholinergic stimulation is a potential therapeutical option. We determined the effects of pyridostigmine bromide, a reversible anticholinesterase agent, on electrocardiographic variables of healthy individuals. METHODS: We carried out a cross-sectional, double blind, randomized, placebo-controlled study. We obtained electrocardiographic tracings in 12 simultaneous leads of 10 healthy young individuals at rest before and after oral administration of 45 mg of pyridostigmine or placebo. RESULTS: Pyridostigmine increased RR intervals (before: 886+/-27 ms vs. after: 1054+/-37 ms) and decreased QTc dispersion (before: 72+/-9 ms vs. after: 45+/-3 ms), without changing other electrocardiographic variables (PR segment, QT interval, QTc, and QT dispersion). CONCLUSION: Bradycardia and the reduction in QTc dispersion induced by pyridostigmine may effectively represent a protective mechanism if these results can be reproduced in individuals with cardiovascular diseases.
Assuntos
Inibidores da Colinesterase/farmacologia , Eletrocardiografia/efeitos dos fármacos , Brometo de Piridostigmina/farmacologia , Adulto , Análise de Variância , Bradicardia/induzido quimicamente , Inibidores da Colinesterase/efeitos adversos , Estudos Transversais , Método Duplo-Cego , Feminino , Humanos , Masculino , Brometo de Piridostigmina/efeitos adversosRESUMO
Obese patients are characterised by several neuroendocrine abnormalities, including characteristically a decrease in growth hormone responsiveness to GH-releasing hormone. In normal subjects, the GH response to GHRH is enhanced by the acetylcholinesterase inhibitor, pyridostigmine. We have studied the effect of this drug on GH secretion in gross obesity. Twelve obese patients were studied (mean weight 156% of ideal) and compared with a group of 8 normal volunteers. Each subject was initially studied on two occasions, in random order, with GHRH (1-29) NH2 100 micrograms iv alone and following pretreatment with pyridostigmine 120 mg orally one hour prior to GHRH. In obese patients, the GH response to GHRH was significantly blunted when compared to controls (GH peak: 20 +/- 4 vs 44 +/- 16 micrograms/l; mean +/- SEM). After pyridostigmine, the response to GHRH was enhanced in the obese subjects, but remained significantly reduced compared to non-obese subjects treated with GHRH and pyridostigmine (GH peak: 30 +/- 5 vs 77 +/- 20 micrograms/l, respectively). In 6 subjects, higher doses of GHRH or pyridostigmine did not further increase GH responsiveness in obese patients. Our results suggest that obese patients have a disturbed cholinergic control of GH release, probably resulting from increased somatostatinergic tone. This disturbed regulation may be responsible, at least in part, for the blunted GH responses to provocative stimuli.