RESUMO
BACKGROUND: Dexmedetomidine and propofol are common sedatives in intensive care units and for interventional procedures. Both may compromise sinus node function and atrioventricular conduction. The objective of this prospective, randomized study is to compare the effect of dexmedetomidine with propofol on sinus node function and atrioventricular conduction. METHODS: In a tertiary care center in Switzerland we included from September 2019 to October 2020 160 patients (65 ± 11 years old; 32% female) undergoing first ablation for atrial fibrillation by cryoballoon ablation or by radiofrequency ablation. Patients were randomly assigned to deep sedation with dexmedetomidine (DEX group) versus propofol (PRO group). A standard electrophysiological study was performed after pulmonary vein isolation with the patients still deeply sedated and hemodynamically stable. RESULTS: Eighty patients each were randomized to the DEX and PRO group. DEX group patients had higher baseline sinus cycle length (1022 vs. 1138 ms; p = 0.003) and longer sinus node recovery time (SNRT400; 1597 vs. 1412 ms; p = 0.042). However, both corrected SNRT and normalized SNRT did not differ. DEX group patients had longer PR interval (207 vs. 186 ms; p = 0.002) and AH interval (111 vs. 95 ms, p = 0.008), longer Wenckebach cycle length of the atrioventricular node (512 vs. 456 ms; p = 0.005), and longer atrioventricular node effective refractory period (390 vs. 344 ms; p = 0.009). QRS width and HV interval were not different. An arrhythmia, mainly atrial fibrillation, was induced in 33 patients during the electrophysiological study, without differences among groups (20% vs. 15%, p = 0.533). CONCLUSIONS: Dexmedetomidine has a more pronounced slowing effect on sinus rate and suprahissian AV conduction than propofol, but not on infrahissian AV conduction and ventricular repolarization. These differences need to be taken into account when using these sedatives. TRIAL REGISTRATION: ClinicalTrials.gov number NCT03844841, 19/02/2019.
Assuntos
Fibrilação Atrial , Sedação Profunda , Dexmedetomidina , Hipnóticos e Sedativos , Propofol , Humanos , Dexmedetomidina/farmacologia , Dexmedetomidina/administração & dosagem , Propofol/administração & dosagem , Propofol/farmacologia , Feminino , Masculino , Estudos Prospectivos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Idoso , Fibrilação Atrial/cirurgia , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/tratamento farmacológico , Pessoa de Meia-Idade , Sedação Profunda/métodos , Nó Sinoatrial/efeitos dos fármacosRESUMO
Objective: This study was conducted to reassess the concepts established over the past 20 years, in particular in the last 5 years, about the use of methylene blue in the treatment of vasoplegic syndrome in cardiac surgery. Methods: A wide literature review was carried out using the data extracted from: MEDLINE, SCOPUS and ISI WEB OF SCIENCE. Results: The reassessed and reaffirmed concepts were 1) MB is safe in the recommended doses (the lethal dose is 40 mg/kg); 2) MB does not cause endothelial dysfunction; 3) The MB effect appears in cases of NO up-regulation; 4) MB is not a vasoconstrictor, by blocking the cGMP pathway it releases the cAMP pathway, facilitating the norepinephrine vasoconstrictor effect; 5) The most used dosage is 2 mg/kg as IV bolus, followed by the same continuous infusion because plasma concentrations sharply decrease in the first 40 minutes; and 6) There is a possible "window of opportunity" for MB's effectiveness. In the last five years, major challenges were: 1) Observations about side effects; 2) The need for prophylactic and therapeutic guidelines, and; 3) The need for the establishment of the MB therapeutic window in humans. Conclusion: MB action to treat vasoplegic syndrome is time-dependent. Therefore, the great challenge is the need, for the establishment the MB therapeutic window in humans. This would be the first step towards a systematic guideline to be followed by possible multicenter studies. .
Objetivo: O presente estudo foi realizado com a finalidade de reavaliar conceitos estabelecidos em 20 anos, com ênfase nos últimos 5 anos, sobre a utilização do azul de metileno no tratamento da síndrome vasoplégica em cirurgia cardíaca. Métodos: Foram considerados dados da literatura utilizando-se três bases de dados (MEDLINE, SCOPUS e ISI Web of Science). Resultados: Os conceitos reavaliados e reafirmados foram: 1) Nas doses recomendadas o AM é seguro (a dose letal é de 40 mg/kg); 2) O AM não causa disfunção endotelial; 3) O efeito do AM só aparece em caso de supra nivelamento do NO; 4) O AM não é um vasoconstritor, pelo bloqueio da via GMPc ele libera a via do AMPc, facilitando o efeito vasoconstritor da norepinefrina; 5) A dosagem mais utilizada é de 2 mg/kg, como bolus EV, seguida de infusão contínua porque as concentrações plasmáticas decaem fortemente nos primeiros 40 minutos, e; 6) Existe uma "janela de oportunidade" precoce para efetividade do AM. Nos últimos cinco anos, os principais desafios foram: 1) Observações de efeitos colaterais; 2) A necessidade de diretrizes, e; 3) A necessidade da determinação de uma janela terapêutica para o uso do AM em humanos. Conclusão: O efeito do AM no tratamento da SV é dependente do tempo, portanto, o grande desafio atual é a necessidade do estabelecimento da janela terapêutica do AM em humanos. Esse seria o primeiro passo para a sistematização de uma diretriz a ser seguida por possíveis estudos multicêntricos. .
Assuntos
Animais , Cães , Camundongos , /farmacologia , Cálcio/farmacologia , Catecolaminas/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Nó Sinoatrial/efeitos dos fármacos , Taquicardia/tratamento farmacológico , Modelos Animais de Doenças , Frequência Cardíaca/fisiologia , Microscopia Confocal , Miocárdio/metabolismo , Miocárdio/patologia , Nó Sinoatrial/metabolismo , Taquicardia/metabolismoRESUMO
We administered arecoline to rats, with experimentally induced chagasic myocarditis, in order to study the sinus node sensitivity to a muscarinic agonist. Sixteen month old rats were inoculated with 200,000 T. cruzi parasites ("Y" strain). Between days 18 and 21 (acute stage), 8 infected rats and 8 age-matched controls received intravenous arecoline as a bolus injection at the following doses: 5.0, 10.0, 20.0, 40.0, and 80.0 mug/kg. Heart rate was recorded before, during and after each dose of arecoline. The remaining 8 infected animals and 8 controls were subjected to the same experimental procedure during the subacute stage, i.e., days 60 to 70 after inoculation. The baseline heart rate, of the animals studied during the acute stage (349 Ý 68 bpm, mean Ý SD), was higher than that of the controls (250 Ý 50 bpm, p < 0.005). The heart rate changes were expressed as percentage changes over baseline values. A dose-response curve was constructed for each group of animals. Log scales were used to plot the systematically doubled doses of arecoline and the induced-heart rate changes. The slope of the regression line for the acutely infected animals (r = - 0.99, b =1.78) was not different from that for the control animals (r = - 0.97, b = 1.61). The infected animals studied during the subacute stage (r = - 0.99, b = 1.81) were also not different from the age-matched controls (r = - 0.99, b = 1.26, NS). Consequently, our results show no pharmacological evidence of postjunctional hypersensitivity to the muscarinic agonist arecoline. Therefore, these results indirectly suggest that the postganglionic parasympathetic innervation, of the sinus node of rats with autopsy proved chagasic myocarditis, is not irreversibly damaged by Trypanosoma cruzi.
Assuntos
Animais , Ratos , Arecolina/farmacologia , Cardiomiopatia Chagásica/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Agonistas Muscarínicos/farmacologia , Nó Sinoatrial/efeitos dos fármacos , Doença Aguda , Sistema Nervoso Parassimpático/efeitos dos fármacos , Sistema Nervoso Parassimpático/parasitologia , Ratos Wistar , Nó Sinoatrial/inervaçãoRESUMO
Evidence has indicated that the sarcoplasmic reticulum (SR) might be involved in the generation of spontaneous electrical activity in atrial pacemaker cells. We report the effect of disabling the SR with ryanodine (0.1 µM) on the sinus node recovery time (SNRT) measured in isolated right atria from 4-6-month-old male Wistar rats. Electrogram and isometric force were recorded at 36.5oC. Two methods for sinus node resetting were used: a) pulse: a single stimulus pulse interpolated at coupling intervals of 50, 65 or 80 percent of the regular spontaneous cycle length (RCL), and b) train: a 2-min train of pulses at intervals of 50, 65 or 80 percent of RCL. Corrected SNRT (cSNRT) was calculated as the difference between SNRT (first spontaneous cycle length after stimulation interruption) and RCL. Ryanodine only slightly increased RCL (<10 percent), but decreased developed force by 90 percent. When the pulse method was used, cSNRT (~40 ms), which represents intranodal/atrial conduction time, was independent of the coupling interval and unaffected by ryanodine. However, cSNRT obtained by the train method was significantly higher for shorter intervals between pulses, indicating the occurrence of overdrive suppression. In this case, ryanodine prolonged cSNRT in a rate-dependent fashion, with a greater effect at shorter intervals. These results indicate that: a) a functional SR, albeit important for force development, does not seem to play a major role in atrial automaticity in the rat; b) disruption of cell Ca2+ homeostasis by inhibition of SR function does not appear to affect conduction; however, it enhances overdrive-induced depression of sinusal automaticity
Assuntos
Animais , Masculino , Ratos , Rianodina/farmacologia , Retículo Sarcoplasmático/efeitos dos fármacos , Nó Sinoatrial/efeitos dos fármacos , Estimulação Elétrica , Ratos Wistar , Fatores de TempoRESUMO
Carbamazepine, a drug used for the treatment of epilepsy and neuralgias, may exert hazardous effects on the cardiac conduction system. We report such a case of symptomatic brady-arrhythmia occurring in a 43-years-old male while on therapy with carbamazepine. Additionally, a literature review is made of previous cases of carbamazepine-induced sinus mode, AV node and His-Purkinje conduction disturbances
Assuntos
Adulto , Humanos , Masculino , Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Nó Sinoatrial/efeitos dos fármacos , Anticonvulsivantes/sangue , Carbamazepina/sangue , Eletrocardiografia Ambulatorial/efeitos dos fármacos , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Síndrome do Nó Sinusal/induzido quimicamente , Síndrome do Nó Sinusal/diagnóstico , Síndrome do Nó Sinusal/fisiopatologia , Nó Sinoatrial/fisiopatologiaRESUMO
En aurículas aisladas de rata se estudió el efecto depresor de la respuesta cronotrópica por los bloqueadores de los canales lentos de calcio a pH 7.39 (grupo control) y pH 7.03 (grupo en acidosis). Se realizaron curvas concentración-respuesta con verapamil, nitrendipina y nifedipina, midiendo la frecuencia de despolarización espontánea luego de 20 minutos de exposición a cada concentración de la droga. Tanto el verapamil como las dihidropiridinas producen una depresión del automatismo sinusal, pero sólo el verapamil presentó un reforzamiento del efecto depresor en acidosis. El cambio en la frecuencia sinusal fue significativamente mayor en el grupo en acidosis que en el control, entre las dosis de 3 x 10**-9 y 10**-7 M. La acidosis aumenta el efecto depresor del verapamil sobre el cronotropismo de manera similar a lo descripto para su efecto sobre el inotropismo. Nuestros resultados sugieren un mecanismo sinérgico para la inhibición del canal de calcio por iones H+ y verapamil, pero no para iones H+ y dihidropiridinas