Event
Special Bioengineering Seminar: Alena Talkachova
Thursday, March 27, 2008
11:00 a.m.-12:00 p.m.
Kay Boardrooms, Kim Engineering Building
Professor Yang Tao
(301) 405-1189
ytao@umd.edu
Short Term Memory and Nonlinear Dynamics of the Heart
Presented by Alena Talkachova
Department of Pharmacology
Institute for Cardiovascular Research
SUNY Upstate Medical University
Sudden cardiac death caused primarily by ventricular fibrillation (VF) is a major public health problem being one of the leading causes of mortality in the Western world. It is believed that under conditions of high-frequency excitation, the beat-to-beat alternation in the action potential duration (APD) of the ventricular myocytes may be a precursor of VF. It has been proposed that APD dynamics in general and the onset of alternans and other complex rhythms in particular, could be understood by analyzing the restitution properties of periodically paced cardiac cells. However, the APD restitution hypothesis is incomplete in its current form partially because it does not account for the presence of short-term memory, which reflects the influence of entire pacing history on the APD.
Although it is recognized that short term memory affects the dynamics of cardiac myocytes in general and the onset of irregular cardiac rhythm in particular, it has never been adequately quantified or measured directly in experiments or numerical simulations, mainly due to the absence of the appropriate techniques. As a result, very little is known about the rate- and species-dependent behavior of short term memory. I will present a new approach that allows one to estimate how much short term memory is present in the cardiac myocytes at different pacing rates. Using patch clamp technique and numerical simulations, I measured short term memory restitution in isolated rabbit and guinea pig ventricular myocytes. In both species short term memory is rate- and species dependent, displaying a biphasic behavior as a function of cycle length. In addition, I will provide some ionic insights into the mechanisms underlying short term memory.
Our recent studies suggest that short term memory also play crucial role in the formation of the spatially discordant alternans (SDA), a dangerous cardiac rhythm that has been linked to VF. To access mechanisms underlying SDA formation, we used high-resolution optical mapping of the epicardial surface of Langendorff-perfused rabbit hearts and tracked the evolution of nodal lines that separate out-of-phase regions of SDA. We found that two mechanisms underlie the development of SDA in the heart, leading to two distinct behaviors of nodal lines. The first mechanism is based on steep conduction velocity (CV) restitution and is associated with small amount of short term memory and stable nodal lines. The second mechanism is associated with large amount of short term memory and characterized by shallow CV restitution and unstable behavior of nodal lines. Our results provide new insight into the mechanisms underlying SDA formation in the rabbit heart and can potentially lead to better therapeutic treatments of VF.
