Cardiac fibrillation: from ion channels to rotors in the human heart

Abstract

Recent new information on the dynamics and molecular mechanisms of electrical rotors and spiral waves has increased our understanding of both atrial fibrillation and ventricular fibrillation. In this brief review, we evaluate the available evidence for the separate roles played by individual sarcolemmal ion channels in atrial fibrillation and ventricular fibrillation, assessing the clinical relevance of such findings. Importantly, although human data support the idea that rotors are a crucial mechanism for fibrillation maintenance in both atria and ventricles, there are clear inherent differences between the 2 chamber types, particularly in regard to the role of specific ion channels in fibrillation. But there also are similarities. This knowledge, together with new information on the changes that take place during disease evolution and between structurally normal and diseased hearts, may enhance our understanding of fibrillatory processes pointing to new approaches to improve disease outcomes.

Figure 1

Wavebreak formation. A. An electrical wavefront moves toward an anatomical obstacle. B. The wavefront attaches to the obstacle and begins to circumnavigate it. C. Under appropriate conditions of excitability, the wavefront breaks into two daughter wavelets that detach from the obstacle, with the consequent formation of a phase singularity (PS) at each broken end. D. The two wavelets curl around their respective PSs and begin to rotate inscribing a figure-8 pattern.

Figure 2

Rotors and fibrillatory conduction. Waves emanating from a high-frequency rotor undergo fibrillatory conduction in a computer model of cardiac ventricular myocytes. Numbers under each frame are milliseconds.

Figure 3

Electrotonic effects of the center of rotation (core) on conduction velocity (CV) action potential duration (APD) and wavelength (WL). During reentry the wavefront adopts a spiral shape with increasing curvature toward the core. A. During sustained reentry, the CV of the wave front slows gradually toward the center (solid arrows), reaching a critical value at the immediate perimeter of the core. As a result, the core remains unexcited. Consequently, a voltage gradient develops between the unexcited core and the neighboring active cells. B. Electrotonic currents between the core and its immediate neighbors shorten APD near the core (broken trace and horizontal arrow). Hence, wavelength (WL= CV × APD) near the core is much shorter than WL far away from the core.

Figure 4

Consequences of transgenic overexpression of I_K1 on action potential characteristics and reentry wavelength and frequency. Top; Left, simulated action potential of wildtype (WT) mouse ventricular myocyte; right, simulated action potential of transgenic (TG) myocyte (grey) superimposed on WT (black). Note significant acceleration of phase-3 repolarization in TG with respect to WT. Bottom, simulation of reentry in WT and TG sheets of ventricular myocytes. Overexpression of I_K1 reduces the spatial extension of the excited state (wavelength) and increases the rotation frequency (WT, 13 Hz; TG, 40 Hz). Curved arrow shows rotation direction; white dot indicates position of the core. Modified from Noujaim et al with permission.