Ações Transmurais Inotrópicas e Antiarrítmicas da Ranolazina em um Modelo Celular da Síndrome do QT Longo Tipo 3

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 (INaL), 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 INaL in mice left ventricular myocytes (LVM). A video detector system monitored sarcomere shortening. At 1 Hz, amiodarone attenuated sarcomere shortening only at 10 µmol/L; at 3 and 5 Hz, 0.1 and 1 µmol/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 INaL 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.

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Cardiovascular Effects of Ranolazine and the Scope for Translational Research: A Current Review of Literature

Fakıoğlu¹,

Yardım-Akaydin²

2022

Frontiers in Cardiovascular Drug Discovery

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The decline in deaths from cardiovascular diseases in line with scientific developments between 1950-2010 was impressive. Despite these significant advances, cardiovascular (CV) diseases remain the leading cause of death worldwide. According to the World Health Organization (WHO) data, 17.9 million people die due to CV diseases every year, which corresponds to 31% of the total deaths worldwide. Therefore, for many CV diseases, there is still a need for improved treatment, and this is only possible with the development of new drugs. Although investments in the previous decade have resulted in the development of many innovative drugs in the treatment of CV diseases, today, pharmaceutical companies are less enthusiastic about developing CV drugs, mainly due to financial and regulatory difficulties. Indeed, today, institutes, associations and even organizations such as WHO are taking over the sponsorship role that pharmaceutical industry players have abandoned. In parallel, cardiovascular pipeline activity is shifting from large pharmaceutical companies to small and medium-sized companies and from fast following drugs to first-in classes. This transformation in CV drug discovery and development reveals significant challenges that require square up to. The aim of this chapter is to discuss the global challenges faced in CV drug discovery and development to find effective solutions.

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Ações Transmurais Inotrópicas e Antiarrítmicas da Ranolazina em um Modelo Celular da Síndrome do QT Longo Tipo 3

Cited by 3 publications

References 11 publications

Recent updates on novel therapeutic targets of cardiovascular diseases

Recent updates on novel therapeutic targets of cardiovascular diseases

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

Cardiovascular Effects of Ranolazine and the Scope for Translational Research: A Current Review of Literature

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