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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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S. Beserra, Samuel [1] ; Roman-Campos, Danilo [1]
Total Authors: 2
[1] Univ Fed Sao Paulo, Paulista Sch Med, Lab CardioBiol, Dept Biophys, Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Web of Science Citations: 0

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)

FAPESP's process: 14/09861-1 - The role of late sodium current in the inherited and acquired cardiac arrhythmias: from the biophysics properties to new therapeutic targets
Grantee:Danilo Roman Campos
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 19/21304-4 - Arrhythmogenic mechanisms in right heart diseases
Grantee:Danilo Roman Campos
Support type: Regular Research Grants