Specific drugs against cardiac arrhythmias
Biomedical Research Foundation of the Academy of Athens (BRFAA)
Cardiac arrhythmias occur in millions of people worldwide and have been related with sudden cardiac death not only of heart failure patients but of healthy individuals as well. The existing pharmacological treatments focus mainly on the prevention of the symptoms rather than the pathogenetic mechanisms of arrhythmias. Additionally, drugs used to prevent arrythmias sometimes might have the opposite effect: they can cause arrhythmias.
In order to develop new specific drugs with greater and long-term effectiveness, it is required: i) in depth understanding of the molecular mechanisms of pathogenesis; ii) selection of the appropriate pharmaceutical compounds that might prevent the dysfunction of these mechanisms; iii) preclinical studies for the evaluation of the specific pharmaceutical compounds using an appropriate experimental model of cardiac arrhythmias.
Taking advantage of the new data that our research group had previously discovered regarding the molecular mechanisms that participate in physiological and pathological cardiac function, as well as the new, valuable for studying cardiac arrhythmias, genetically modified mouse model that we had created (junctin knockout, JKO), we performed a detailed characterization of two novel pharmaceutical compounds that were selected for their action on the molecular mechanisms of pathogenesis. Specifically, arrhythmias were induced in the JKO mice followed by administration of either of the two compounds. Extensive in vivo (intact mice) and in vitro (isolated cardiomyocytes) analysis demonstrated that one of the two substances significantly reduced arrhythmias at both levels (in vivo and in vitro). These findings suggest that the specific chemical compound could have a promising role in combating arrhythmias in the long run and merits further in depth analysis.
Final report (in Greek)
Despina Sanoudou, Assistant Professor, Molecular Biology Department, Biomedical Research Foundation of the Academy of Athens Department of Pharmacology, Medical School, National and Kapodistrian University of Athens
Evangelia Kranias, Professor, Department of Pharmacology and Cell Biophysics, Cardiovascular Center of Excellence, College of Medicine, University of Cincinnati Molecular Biology Department, Biomedical Research Foundation of the Academy of Athens
Dimitrios Kremastinos, Emeritus Professor, Medical School, National and Kapodistrian University of Athens
Nikolaos Kostomitsopoulos, Staff Research Scientist – Professor Level, Center of Experimental Surgery, Biomedical Research Foundation of the Academy of Athens
Christos Tzimas, Postdoctoral Research Fellow, Molecular Biology Laboratory, Biomedical Research Foundation of the Academy of Athens