NDLI: Ischemic modulation of vulnerable period and the effects of pharmacological treatment of ischemia-induced arrhythmias: a simulation study

Content Provider	IEEE Xplore Digital Library
Author	Cimponeriu, A. Starmer, C.F. Bezerianos, A.
Copyright Year	1964
Abstract	First identified in the 1930s (Ferris et al., 1936 and Wiggers and Wegria, 1939), the concept of vulnerability applies perfectly to biological oscillators. We can safely say that vulnerability is an inherent property of any excitable media. The duration of vulnerable period (VP) (the time interval during which single stimuli can initiate self-sustaining propagation) is sensitive to medium properties and stimulus parameters (stimulus field, timing behind the conditioning wave, and stimulus amplitude). Apart from medium properties and stimulus characteristics, heart vulnerability is affected by any intervention targeting the excitatory and recovery process. Therefore, we can expect that any pathological condition disturbing heart excitation or tissue recovery will most probably alter the duration of VP. In this paper, we shall explore the implications of ischemia and one of the arrhythmia counteracting methods widely used in clinical practice-antiarrhythmic drugs-in changing the boundaries of VP. The Cardiac Arrhythmia Suppression Trial (CAST) studies, as well as classification based on functional characteristics, revealed the arrhythmogenic potential of both Class I and Class III agents, but failed to identify the proarrhythmic mechanisms. This study presents results from a mathematical model (Cimponeriu et al., 2001) of the ventricle based on Luo-Rudy cellular formulation (Luo and Rudy, 1991) modified for studying the ischemic modulation of VP and the effects of pharmacological treatment of ischemia-induced arrhythmia. Simulations revealed the link between the cellular antiarrhythmic properties and the proarrhythmic effect at the multicellular level in the case of Na/sup +/ channel blockade. Na/sup +/ channel blockade delayed recovery of cellular excitability, but also introduced a nonuniform dispersion of refractoriness along the cardiac fiber that can serve as a substrate for initiating a new arrhythmia. Our initial analysis proved that fast unbinding rates are essential in reducing the proarrhythmic potential of Class I drugs. However, further investigations led us to believe that binding properties are equally important. An antiarrhythmic drug with high affinity for drug-channel complex formation elicits a higher level of blockade per time unit. Under this light, we hypothesize that even the modern, fast unbinding drugs are not necessarily safe.
Sponsorship	IEEE Engineering in Medicine and Biology Society
Page Count	10
File Size	600123
Starting Page	168
Ending Page	177
File Format	PDF
ISSN	00189294
Volume Number	50
Issue Number	2
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2003-02-01
Publisher Place	U.S.A.
Access Restriction	One Nation One Subscription (ONOS)
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	Drugs Biological system modeling Heart Ischemic pain Physics Displays Oscillators Timing Pathology Mathematical model
Content Type	Text
Resource Type	Article
Subject	Biomedical Engineering

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