Heart Care Info - Heart Disease Prevention & Treatment

The role of dynamic instability and wavelength in arrhythmia maintenance as revealed by panoramic imaging with blebbistatin versus 2, 3-butanedione monoxime

Q Lou, W Li... - American Journal of Physiology- ..., 2011 - Am Physiological Soc Abstract Introduction: Unlike other excitation-contraction uncouplers, blebbistatin has few electrophysiological side effects, and has gained increasing acceptance as an excitation-contraction uncoupler in optical mapping experiments. However, the possible role of ...

Introduction: Unlike other excitation-contraction uncouplers, blebbistatin has few electrophysiological side effects, and has gained increasing acceptance as an excitation-contraction uncoupler in optical mapping experiments. However, the possible role of blebbistatin in ventricular arrhythmia has hitherto been unknown. Furthermore, experiments with blebbistatin and 2,3-butanedione monoxime (BDM) offer an opportunity to assess the contribution of dynamic instability and wavelength of impulse propagation to the induction and maintenance of ventricular arrhythmia. Methods and Results: Recordings of monophasic action potentials were used to assess effects of blebbistatin in Langendorff-perfused rabbit hearts (n = 5). Additionally, panoramic optical mapping experiments were conducted in rabbit hearts (n = 7) which were sequentially perfused with BDM, then washed out, and subsequently perfused with blebbistatin. The susceptibility to arrhythmia was investigated using shock-on-T protocol. We found that (1) application of blebbistatin did not change action potential duration (APD) restitution; (2) BDM flattened APD restitution curve, and reduced the wavelength; (3) incidence of sustained arrhythmia was much lower under blebbistatin than under BDM (2/123 vs. 23/99). Arrhythmia under BDM was mostly stable reentry, while the arrhythmia under blebbistatin was unstable and terminated spontaneously. Conclusions: The lower susceptibility to arrhythmia under blebbistatin than under BDM indicates blebbistatin has less effects on the arrhythmia dynamics. A steep restitution slope under blebbistatin is associated with higher dynamic instability, manifested by the higher incidence of not only wave breaks but also wave extinctions. This relatively high dynamic instability leads to the self-termination of arrhythmia, because of the sufficiently long wavelength under blebbistatin.