Impact of pacing frequency in amiodarone interaction with cardiomyocytes near physiological temperature in health and disease conditions

Autor(es)

S. Beserra, Samuel ^[1] ; Roman-Campos, Danilo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Paulista Sch Med, Lab CardioBiol, Dept Biophys, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY; v. 128, n. 4 NOV 2020.
• Citações Web of Science: 0

Resumo

Long QT syndrome type 3 (LQT-3) is a disease related to abnormal cardiac sodium channel function (Nav 1.5), usually due to augmented late sodium current (I-NaL), and may lead to ventricular fibrillation. Amiodarone is approved for ventricular fibrillation. Thus, we investigated whether pacing frequency impacts the ability of amiodarone to reverse the arrhythmic phenotype observed in LQT-3. Anemone neurotoxin 2 (ATX-II, here named only ATX) was used to enhance I-NaL in mice left ventricular myocytes (LVM). A video detector system monitored sarcomere shortening. At 1 Hz, amiodarone attenuated sarcomere shortening only at 10 mu mol/L; at 3 and 5 Hz, 0.1 and 1 mu mol/L amiodarone also reduced sarcomere shortening. However, no effect of amiodarone was observed on time to 50% of sarcomere contraction and relaxation. In LVM exposed to ATX (10 nmol/L), an arrhythmic phenotype was observed, and it was more severe when cells were paced at 1 Hz. Amiodarone failed to reverse the ATX induced phenotype at different pacing frequencies. Thus, our results suggest that amiodarone's ability to reverse arrhythmias induced by augmentation of I-NaL is limited. These findings suggest further experimentation will be required to clarify whether a clinical effect can be ascribed to an effect of amiodarone on other ion channels in LQT-3. (AU)

• Processo FAPESP: 14/09861-1 - Papel da corrente tardia de sódio nas arritmias cardíacas herdadas e adquiridas: da biofísica à procura de novos alvos terapêuticos
• Beneficiário: Danilo Roman Campos
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 19/21304-4 - Mecanismos arritmogênicos em doenças do coração direito
• Beneficiário: Danilo Roman Campos
• Modalidade de apoio: Auxílio à Pesquisa - Regular