Intracellular calcium dynamics at the core of endocardial stationary spiral waves in Langendorff-perfused rabbit hearts.
ABSTRACT In vitro models of sustained monomorphic ventricular tachycardia (MVT) are rare and do not usually show spiral reentry on the epicardium. We hypothesized that MVT is associated with the spiral wave in the endocardium and that this stable reentrant propagation is supported by a persistently elevated intracellular calcium (Ca(i)) transient at the core of the spiral wave. We performed dual optical mapping of transmembrane potential (V(m)) and Ca(i) dynamics of the right ventricular (RV) endocardium in Langendorff-perfused rabbit hearts (n = 12). Among 64 induced arrhythmias, 55% were sustained MVT (>10 min). Eighty percent of MVT showed stationary spiral waves (>10 cycles, cycle length: 128 +/- 14.6 ms) in the endocardial mapped region, anchoring to the anatomic discontinuities. No reentry activity was observed in the epicardium. During reentry, the amplitudes of V(m) and Ca(i) signals were higher in the periphery and gradually decreased toward the core. At the core, maximal V(m) and Ca(i) amplitudes were 42.95 +/- 5.89% and 43.95 +/- 9.46%, respectively, of the control (P < 0.001). However, the trough of the V(m) and Ca(i) signals at the core were higher than those in the periphery, indicating persistent V(m) and Ca(i) elevations during reentry. BAPTA-AM, a calcium chelator, significantly reduced the maximal Ca(i) transient amplitude and prevented sustained MVT and spiral wave formation in the mapped region. These findings indicate that endocardial spiral waves often anchor to anatomic discontinuities causing stable MVT in normal rabbit ventricles. The spiral core is characterized by diminished V(m) and Ca(i) amplitudes and persistent V(m) and Ca(i) elevations during reentry.
Article: Nonstationary vortexlike reentrant activity as a mechanism of polymorphic ventricular tachycardia in the isolated rabbit heart.[show abstract] [hide abstract]
ABSTRACT: Ventricular tachycardia may result from vortexlike reentrant excitation of the myocardium. Our general hypothesis is that in the structurally normal heart, these arrhythmias are the result of one or two nonstationary three-dimensional electrical scroll waves activating the heart muscle at very high frequencies. We used a combination of high-resolution video imaging, electrocardiography, and image processing in the isolated rabbit heart, together with mathematical modeling. We characterized the dynamics of changes in transmembrane potential patterns on the epicardial surface of the ventricles using optical mapping. Image processing techniques were used to identify the surface manifestation of the reentrant organizing centers, and the location of these centers was used to determine the movement of the reentrant pathway. We also used numerical simulations incorporating Fitzhugh-Nagumo kinetics and realistic heart geometry to study how stationary and nonstationary scroll waves are manifest on the epicardial surface and in the simulated ECG. We present epicardial surface manifestations (reentrant spiral waves) and ECG patterns of nonstationary reentrant activity that are consistent with those generated by scroll waves established at the right and left ventricles. We identified the organizing centers of the reentrant circuits on the epicardial surface during polymorphic tachycardia, and these centers moved during the episodes. In addition, the arrhythmias that showed the greatest movement of the reentrant centers displayed the largest changes in QRS morphology. The numerical simulations showed that stationary scroll waves give rise to monomorphic ECG signals, but nonstationary meandering scroll waves give rise to undulating ECGs characteristic of torsade de pointes. Polymorphic ventricular tachycardia in the healthy, isolated rabbit heart is the result of either a single or paired ("figure-of-eight") nonstationary scroll waves. The extent of the scroll wave movement corresponds to the degree of polymorphism in the ECG. These results are consistent with our numerical simulations that showed monomorphic ECG patterns of activity for stationary scroll waves but polymorphic patterns for scroll waves that were nonstationary.Circulation 06/1995; 91(9):2454-69. · 14.74 Impact Factor