Transmural Ultrasound-based Visualization of Patterns of Action Potential Wave Propagation in Cardiac Tissue

The pattern of action potential propagation during various tachyarrhythmias is strongly suspected to be composed of multiple re-entrant waves, but has never been imaged in detail deep within myocardial tissue. An understanding of the nature and dynamics of these waves is important in the development of appropriate electrical or pharmacological treatments for these pathological conditions. We propose a new imaging modality that uses ultrasound to visualize the patterns of propagation of these waves through the mechanical deformations they induce. The new method would have the distinct advantage of being able to visualize these waves deep within cardiac tissue. In this article, we describe one step that would be necessary in this imaging process—the conversion of these deformations into the action potential induced active stresses that produced them. We demonstrate that, because the active stress induced by an action potential is, to a good approximation, only nonzero along the local fiber direction, the problem in our case is actually overdetermined, allowing us to obtain a complete solution. Use of two- rather than three-dimensional displacement data, noise in these displacements, and/or errors in the measurements of the fiber orientations all produce substantial but acceptable errors in the solution. We conclude that the reconstruction of action potential-induced active stress from the deformation it causes appears possible, and that, therefore, the path is open to the development of the new imaging modality

Heterogeneity of ventricular fibrillation dominant frequency during global ischemia in isolated rabbit hearts

Introduction: Ventricular fibrillation (VF) studies show that ECG-dominant frequency (DF) decreases as ischernia develops. This study investigates the contribution of the principle ischernic metabolic components to this decline. Methods and Results: Rabbit hearts were Langendorff-perfused at 40 mL/min with Tyrode's solution and loaded with RH237. Epicardial optical action potentials were recorded with a photodiode array (256 sites, 15 x 15 mm). After 60 seconds of VF (induced by burst pacing), global ischernia was produced by low flow (6 mL/min), or the solution changed to impose hypoxia (95 % N-2/5% CO2), low pH(o) (6.7, 80 % O-2/20% CO2), or raised [K+](o) (8 mM). DF of the optical signals was determined at each site. Conduction velocity (CV), action potential duration (APD90), effective refractory period (ERP), activation threshold, dV/dt(max) and membrane potential were measured in separate experiments during ventricular pacing. During VF, ischernia decreased DF in the left ventricle (LV) (to [58 6] %, P < 0.001), but not the right (RV) ([93 5]%). Raised [K+]o reproduced this DF pattern (LV: [67 +/- 12]%, P < 0.001; RV: [95 91%). LV DF remained elevated in hypoxia or low pH,,. During ventricular pacing, ischernia decreased CV in LV but not RV. Raised [K+](o) did not change CV in either ventricle. Ischernia and raised [K+](o) shortened APD90 without altering ERP. LV activation threshold increased in both ischernia and raised [K+](o) and was associated with diastolic depolarization and decreased dV/dt(max),Conclusions: These results suggest that during VF, decreased ECG DF in global ischemia is largely due to elevated [K+](o) affecting the activation thresholds in the LV rather than RV

Optogenetics design of mechanistically-based stimulation patterns for cardiac defibrillation

Current rescue therapies for life-threatening arrhythmias ignore the pathological electro-anatomical substrate and base their efficacy on a generalized electrical discharge. Here, we developed an all-optical platform to examine less invasive defibrillation strategies. An ultrafast wide-field macroscope was developed to optically map action potential propagation with a red-shifted voltage sensitive dye in whole mouse hearts. The macroscope was implemented with a random-access scanning head capable of drawing arbitrarily-chosen stimulation patterns with sub-millisecond temporal resolution allowing precise epicardial activation of Channelrhodopsin2 (ChR2). We employed this optical system in the setting of ventricular tachycardia to optimize mechanistic, multi-barrier cardioversion/defibrillation patterns. Multiple regions of conduction block were created with a very high cardioversion efficiency but with lower energy requirements as compared to whole ventricle interventions to interrupt arrhythmias. This work demonstrates that defibrillation energies can be substantially reduced by applying discrete stimulation patterns and promotes the progress of current anti-arrhythmic strategies