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Thesis topic proposal
 
The clinical and experimental examination of cardiac arrhythmias and the investigation of the mechanism of the cardiac muscle contractility

THESIS TOPIC PROPOSAL

Institute: University of Szeged
theoretical medicine
Graduate School of Multidisciplinar Medical Scienses

Thesis supervisor: Attila Farkas
Location of studies (in Hungarian): English
Abbreviation of location of studies: ÁOK


Description of the research topic:

Dr. Attila Farkas’ main scientific interest is the clinical and experimental examination of cardiac arrhythmias and the investigation of the mechanism of the cardiac muscle contractility. He does research in the field of Cardiovascular Pharmacology and Physiology; he is most interested in the examination of the development of arrhythmia, in the proarrhythmic effects of drugs and in the mechanism of the cardiac muscle contraction. Proarrhythmia is when a drug increases the incidence of arrhythmias already present in the patient or when a drug induces arrhythmias not seen in the patient earlier. The most examined drug-induced arrhythmia is the so-called Torsades de Pointes type ventricular tachycardia (TdP). TdP is dangerous, because it may deteriorate into ventricular fibrillation leading to sudden cardiac death. The proarrhythmic activity of every newly developed drug has to be tested. Unfortunately, there are many factors whose roles are not known properly in the development of proarhythmias. Moreover, the presently available pre-clinical bioessays of proarrhythmia are not specific and sensitive enough to test proarrhythmic activity of drugs.
Main scientific aims of Dr. Attila Farkas’ are the identification the endogenous contributing factors of proarrhytmia, the investigation of the role of Ca2+ handling in arrhythmias and the examination/development preclinical proarrhythmia models for drug-screening. In his earlier studies, he examined the proarrhythmic role of ɑ1 adrenoceptor stimulation1, ventricular stretch1, autonomic nervous system (under submission), and the importance of ventricular electric instability in the development of drug-induced proarrhythmia2. Furthermore, he studied the Ca2+ handling in the cardiac muscle contraction3, 4 and in the development of proarrhythmias5.
Dr. Attila Farkas has been contributing to the development, characterization and validation of various experimental proarrhythmia models. He quantified first the variability of ECG intervals during arrhythmia, and he characterized the development of TdP in a frequently used in vivo anaesthetized animal proarrhythmia model2. He compared the cardiac muscle contractility in different species concluding the species-dependent functioning of the Na+/Ca2+ exchanger3, 4. He published his results in a review paper with the highlights of the repolarization-related proarrhythmia studies in the literature6. Most recently, Dr. Farkas has been developing another in vitro proarrhythmia model, which utilizes isolated, Langendorff-perfused rabbit hearts based on the decrease of the repolarisation reserve. This would have great impact on safety pharmacology investigations in the pharmaceutical industry. Furthermore, he plans to investigate the role of the athlete’s heart in the development of proarrthythmia in order to better understand the sudden cardiac events among athletes.

References:

1. Farkas AS, Acsai K, Toth A, Dezsi L, Orosz S, Forster T, Csanady M, Papp JG, Varro A, Farkas A. Importance of extracardiac alpha1-adrenoceptor stimulation in assisting dofetilide to induce torsade de pointes in rabbit hearts. Eur J Pharmacol. 2006;537:118-125
2. Farkas AS, Rudas L, Makra P, Csik N, Lepran I, Forster T, Csanady M, Papp JG, Varro A, Farkas A. Biomarkers and endogenous determinants of dofetilide-induced torsades de pointes in alpha(1) -adrenoceptor-stimulated, anaesthetized rabbits. Br J Pharmacol. 2010;161:1477-1495
3. Szentandrássy N, Birinyi P, Szigeti G, Farkas A, Magyar J, Toth A, Csernoch L, Varró A, Nánási PP. Sea0400 fails to alter the magnitude of intracellular ca(2+) transients and contractions in langendorff-perfused guinea pig heart. Naunyn Schmiedebergs Arch Pharmacol. 2008;378:65-71
4. Farkas AS, Acsai K, Nagy N, Toth A, Fulop F, Seprenyi G, Birinyi P, Nanasi PP, Forster T, Csanady M, Papp JG, Varro A, Farkas A. Na(+)/ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart. Br J Pharmacol. 2008;154:93-104
5. Farkas AS, Makra P, Csik N, Orosz S, Shattock MJ, Fulop F, Forster T, Csanady M, Papp JG, Varro A, Farkas A. The role of the na+/ca2+ exchanger, i(na) and i(cal) in the genesis of dofetilide-induced torsades de pointes in isolated, av-blocked rabbit hearts. Br J Pharmacol. 2009;156:920-932
6. Farkas AS, Nattel S. Minimizing repolarization-related proarrhythmic risk in drug development and clinical practice. Drugs. 2010;70:573-603

Required language skills: English
Number of students who can be accepted: 1

Deadline for application: 2017-07-31

 
All rights reserved © 2007, Hungarian Doctoral Council. Doctoral Council registration number at commissioner for data protection: 02003/0001. Program version: 1.2357 ( 2017. V. 15. )