Reentry has been recognized as the major mechanism responsible for ventricular arrhythmias. Because reentrant tachycardias can lead to ventricular fibrillation and sudden death, it is important to understand their pathophysiology. Reentrant arrhythmias may occur in the absence of an anatomically predetermined circuit. Mechanisms proposed by experimental electrophysiologists to explain functionally determined reentry are based on the concept of circulation of propagation around a functional """"""""hole"""""""". On the other hand, theoretical and experimental studies based on wave propagation in other types of excitable media, such as the Belousov-Zhabotinsky reaction, show that self-sustained rotating activity, in the form of spiral waves, is demonstrable in homogeneous systems. The overall objective of this study is to use newly developed concepts derived from theoretical studies on the dynamics of spiral waves in excitable media to provide insight into the electrophysiological bases of ventricular reentrant arrhythmias. The applicability of such concepts to the understanding of mechanisms of arrhythmias has been recently supported by experimental studies reported from our laboratory (1-3).
The specific aims are: 1) To develop an optical mapping system with optimal spatio-temporal resolution for the direct observation of spiral waves in isolated ventricular muscle. 2) To determine the mechanisms of stationary and non-stationary spiral waves; and 3) To determine the dynamics of spiral waves during perturbations in the form of propagating waves initiated by electrical stimulation. The following hypotheses will be tested: 1) Spiral waves may exhibit either stationary or non- stationary states depending on: a) electrophysiological parameters: characteristics of phase 0 and action potential duration; b) interaction of the rotating waves with the boundaries of the excitable medium; 2) A non-stationary spiral wave drift (it may change in position). However, the presence of small heterogeneities may serve to anchor the rotating activity and convert a non-stationary spiral wave into a stationary one; 3) The core of a spiral wave may be shifted in place as a result of just- threshold stimulation. The direction and velocity of the drift will depend on the phase of the spiral wave and the rate of stimulation. However, stimulation applied directly at the core may produce drift or termination in a phase-independent manner. Our preliminary results strongly suggest that high resolution optical mapping should allow a detailed quantitative study of spiral waves in isolated ventricular myocardium. The proposed experiments will give direct and accurate answers about the cellular basis of sustained reentry in isolated two- dimensional cardiac muscle and nay provide insight into the pathophysiology of ventricular tachycardia.
| Beaumont, J; Davidenko, N; Davidenko, J M et al. (1998) Spiral waves in two-dimensional models of ventricular muscle: formation of a stationary core. Biophys J 75:1-14 |
| Gray, R A; Jalife, J; Panfilov, A et al. (1995) Nonstationary vortexlike reentrant activity as a mechanism of polymorphic ventricular tachycardia in the isolated rabbit heart. Circulation 91:2454-69 |
| Gray, R A; Jalife, J; Panfilov, A V et al. (1995) Mechanisms of cardiac fibrillation. Science 270:1222-3;author reply 1224-5 |
| Davidenko, J M; Delmar, M; Beaumont, J et al. (1994) Electrotonic inhibition and active facilitation of excitability in ventricular muscle. J Cardiovasc Electrophysiol 5:945-60 |
| Davidenko, J M (1993) Spiral wave activity: a possible common mechanism for polymorphic and monomorphic ventricular tachycardias. J Cardiovasc Electrophysiol 4:730-46 |
