Structural Heterogeneity in the Ventricular Wall Plays a Significant Role in the Initiation of Stretch-Induced Arrhythmias in Perfused Rabbit Right Ventricular Tissues and Whole Heart Preparations

Abstract

Rationale: Mechanical stress is known to alter the electrophysiological properties of the myocardium and may trigger fatal arrhythmias when an abnormal load is applied to the heart. Objective: We tested the hypothesis that the structural heterogeneity of the ventricular wall modulates globally applied stretches to create heterogeneous strain distributions that lead to the initiation of arrhythmias. Methods and Results: We applied global stretches to arterially perfused rabbit right ventricular tissue preparations.The distribution of strain (determined by marker tracking) and the transmembrane potential (measured by optical mapping) were simultaneously recorded while accounting for motion artifacts. The 3D structure of the preparations was also examined using a laser displacement meter. To examine whether such observations can be translated to the physiological condition, we performed similar measurements in whole heart preparations while applying volume pulses to the right ventricle. At the tissue level, larger stretches (>20%) caused synchronous excitation of the entire preparation, whereas medium stretches (10% and 15%) induced focal excitation. We found a significant correlation between the local strain and the local thickness, and the probability for focal excitation was highest for medium stretches. In the whole heart preparations, we observed that such focal excitations developed into reentrant arrhythmias.

Simultaneous optical mapping of transmembrane potential and wall motion in isolated, perfused whole hearts

“…Seo et al 16 recently employed a marker tracking scheme together with optical mapping to estimate strain distributions and track electrical propagation in cardiac preparations. For each video frame, they used a cross correlation technique similar to ours to find the displacements of epicardial markers relative to a reference video frame.…”

“…They used the method to relate deformation to arrhythmia initiation. 16 In our method, ring-shaped material markers are attached to the isolated heart, which is stained with voltage sensitive dye (VSD). V m signals are obtained by recording the fluorescence emitted from within each marker and using a ratiometric technique to minimize motion artifact.…”

Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

“…One concern regarding single cell experiments is that techniques for stretching isolated adult cardiomyocytes are technically quite difficult, and coupling these techniques with electrophysiological study present a difficult hurdle [110]. Depending on the scientific question, there is interest in testing isolated adult cells as singles, doublets, or as slices or strips of tissue [88,[111][112][113]] Still, precise but population-level electrophysiological studies of electrically coupled cells under precise and physiological mechanical strain conditions remains challenging.…”

Remodeling of cardiac passive electrical properties and susceptibility to ventricular and atrial arrhythmias

“…A local stretch therefore can alter the local pathways of activation (Dhein et al, 2014). On the other hand, it has been shown that structural heterogeneities can affect stretch-induced ventricular arrhythmia (Seo et al, 2010). Wall thickness can be heterogeneously distributed over the ventricle, which will result in a regional modulation of a mechanical stimulus so that regional strain varies.…”