The mechanical contractions of the heart are triggered by electrical waves of excitation propagating through cardiac tissue. Abnormalities in the wave propagation, including fast and chaotic propagation in the heart, may lead to fatal cardiac arrhythmias, such as ventricular fibrillation (VF).
VF is believed to be the primary reason underlying sudden cardiac death, a major public health problem, and one of the leading causes of mortality in the Western world. While it is generally agreed that the likeliest mechanism of VF is reentry, a major challenge in the field of cardiac electrophysiology is to understand how events at the cellular and molecular levels translate into arrhythmic behavior in the whole heart.
The general goal of my group is to investigate the electrical activity of cardiac cells and whole heart from a nonlinear dynamics perspective, aiming to reveal mechanisms of complex cardiac rhythms leading to VF and sudden cardiac death.
Optical mapping of the heart
We use high-resolution optical mapping technique to record electrical activity (action potentials) from the epicardial surface of the small mammalian hearts with the help of voltage-sensitive dyes. Our dual-cameras set up allows recording from more than 80 percent of the heart surface.
The spatio-temporal dynamics of the action potentials propagating in the heart is analyzed during periodic pacing as well as during abnormal cardiac rhythms (VF). We aim to characterize restitution properties of the periodically paced heart and reveal the mechanisms leading to the onset of VF.
Whole cell patch clamp
We use whole cell patch clamp technique to investigate electrophysiological properties of myocytes isolated by means of enzyme dissociation from the different regions of small mammalian hearts.
First, we record and analyze the kinetics of different ionic currents flowing through the cell membrane, and investigate their role in the action potentials characteristics. Second, we determine the restitution properties of action potentials of isolated myocytes at different pacing rates during normal and abnormal responses (alternans). We aim to understand the transition from the normal responses to alternans at the cellular level.
We perform 0D and 2D numerical simulations of the physiological ionic models of cardiac action potentials in different species aiming to complement and further drive our previously described experiments. We use a novel approach reflecting the influence of ionic currents kinetics on the dynamic characteristics of periodically paced cardiac myocytes to achieve a good qualitative and quantitative agreement with experimental data.
S. Mironov, J. Jalife, E.G. Tolkacheva. "The role of conduction velocity restitution and short term memory in the development of APD alternans in isolated rabbit hearts", Circulation, 118:17-25, 2008. (abstract)
E.G. Tolkacheva "The rate- and species-dependence of short-term memory in cardiac myocytes" J. Biol. Physics, 33:35-37, 2007.
M. Cerrone, S.F. Noujaim, E.G. Tolkacheva, A.Talkachou, O. Berenfeld, J. Anumonwo, S. Pandit, K. Vikstrom, C. Napolitano, S.G. Priori and J. Jalife, Arrtythmogenic mechanisms in a mouse model of catecholaminergic polymorphic ventricular tachycardia, Circ. Res. 9:1039-1048, 2007. (abstract)
D.G. Schaeffer, J.W. Cain, D.J. Gauthier, S.S. Kalb, R.A. Oliver, E.G. Tolkacheva, W. Ying, W. Krassowska, "An ionically based mapping model with memory for cardiac restitution" Bull Math Bio, 69:459-82, 2007. (abstract)
E.G. Tolkacheva, J.M.B. Anumonwo, J.J. Jalife "Action potential duration restitution portraits of mammalian ventricular myocytes: role of calcium current", Biophys J. 91(7):2735, 2006. (abstract)
V. Muñoz, R. Vaidyanathan, E.G. Tolkacheva, A. Dhamoon, S. Taffet, J.M.B. Anumonwo "Kir2.3 Isoform Confers pH Sensitivity to Kir2.1-Kir2.3 Heteromeric Channels, Heart Rhythm, 4:487-496, 2007. (abstract)
S.S. Kalb, E.G. Tolkacheva, D.G. Schaeffer, D.J. Gauthier, W. Krassowska "Restitution in mapping models with an arbitrary amount of memory", Chaos v. 15, p. 023701, 2005. (abstract)
J.W. Cain, E.G. Tolkacheva, D.G. Schaeffer, D.J. Gauthier "Rate-dependent waveback velocity of cardiac action potentials in a one-dimensional cable", Phys. Rev. E. v.70, p.061906, 2004. (abstract)
E.G. Tolkacheva, M.M. Romeo, M. Guerraty, D.J. Gauthier "Condition for alternans and its control in two-dimensional mapping model of paced cardiac tissue", Phys. Rev. E. v.69, p. 031904, 2004. (abstract)
S.S. Kalb, H. Dobrovolny, E.G. Tolkacheva, S.F. Idriss, W. Krassowska, D.J. Gauthier "The restitution portrait: a new method for investigating rate-dependence restitution", J. Cardiovasc. Electrophysiol., v.15, N6, p.698, 2004. (abstract)
E.G. Tolkacheva, M.M. Romeo, and D.J. Gauthier "Control of cardiac alternans in a mapping model with memory", Physica D, v.194, p.385, 2004.
E.G. Tolkacheva, D.G. Schaeffer, D.J. Gauthier, and W. Krassowska, "Condition for alternans and stability of the 1:1 response pattern in a memory model of paced cardiac dynamics", Phys. Rev. E. v.67, p.031904, 2003. (abstract)