AREA OF EXPERTISE and PRIMARY INTEREST
Experimental techniques
- Simultaneous action potential (microelectrode) and
contractile activity recordings in frog atrial fibers and
guinea-pig papillary muscles to investigate mechanisms
of action of antiarrhythmic drugs.
- Voltage-clamp recordings of the integral sodium current
in single Purkinje and ventricular cells to determine rate-dependent
characteristics of drug-channel interactions.
- Recordings of single sodium and potassium channels activity in the cell-attached configuration.
- In vivo experiments on open-chest dogs to record local electrograms with the aim to determine effects of antiarrhythmic drugs on conduction delays, and to record monophasic action potentials using newly developed technique aimed at revealing transmural electrical heterogeneity in ventricular myocardium.
- Use of an arterially-perfused ventricular wedge preparation to confirm theoretically predicted spatial resolution of the unipolar monophasic action potential recording technique.
Experimental techniques
- Development of data acquisition systems for physiological experiments (single ionic channel and action potential recording and data analysis) using Pascal & C in DOS & CP/M environment.
- Computational models of channel-receptor interactions implementing modulated- and guarded-receptor models bundled with either HH or Markov (single channels) ionic current models.
- Computer modeling of transient outward current, calcium current and sodium-calcium exchange current based on recently obtained experimental data.
- Integration of ionic current models into full cellular model of electrical activity using C++ & MathCAD.
- Computer simulation of ECG, monophasic action potential, and normal and abnormal propagation of excitation in myocardial (Luo-Rudy I & II) mono- and bi-domain 1-D and 2-D models.
- Extensive software development using Pascal and C in DOS, using C in UNIX including X-windows visual interfaces and system management, and using Borland C++ Builder in Windows 95 & NT.
CURRENT RESEARCH
Development of the ionic model of the canine ventricular action potential that is capable of reproducing the correct behavior of all four ventricular cell types (RV Epicardial, LV Epicardial, M cell, and Endocardial). Currently, the model is being tested against an extensive database of experimental data obtained in a variety of experimental conditions (ionic environment, known cardioactive drugs, voltage-clamp data). The final goal is to build a model that is accurate enough to predict and investigate mechanisms of potential pro- and antiarrhythmic effects of novel cardioactive compounds.
Major Publications
- Dumaine R, Towbin JA, Brugada P, Vatta M, Nesterenko DV, Nesterenko VV, Brugada J, Brugada R, Antzelevitch C. "Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent", Circ.Res., v.85, pp.803-809 (1999).
PubMed ID: 10532948
- Weissenburger J, Nesterenko VV, Antzelevitch C. "Transmural heterogeneity of ventricular repolarization under baseline and Long QT conditions in the canine heart in vivo. Torsade de Pointes develops with halothane but not pentobarbital anesthesia", J.Cardiovasc.Electrophysiol., v.11, pp.290-304 (2000).
PubMed ID: 10749352
- Nesterenko VV, Weissenburger J, Antzelevitch C. "Cellular basis and method for recording the monophasic action potential", Letter to the Editor, J.Cardiovasc.Electrophysiol., v.8, pp.946-951 (2000).
- Antzelevitch C, Muzikant AL, Rice JJ, Chen G, Nesterenko VV, Colatsky T. "Influence of transmural repolarization gradients on the electrophysiology and pharmacology of ventricular myocardium. Cellular basis for the Brugada and Long QT syndromes", Philosophical Transactions of the Royal Society (London), v.359: 1201-1216 (2001).
- Zygmunt AC, Eddlestone GT, Thomas GP, Nesterenko VV, Antzelevitch C. "Larger late sodium conductance in M cells contributes to electrical heterogeneity in canine ventricle", Am.J.Physiol., v.281: H689-H697 (2001).
PubMed ID: 11454573
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