Library

Notes: Unique Properties of Optical Action Potentials. Introduction: Optical mapping with voltage-sensitive dyes has made it possible to record cardiac action potentials with high spatial resolution that is unattainable by conventional techniques. Optically recorded signals possess distinct properties that differ importantly from electrograms recorded with extracellular electrodes or action potentials recorded with microelectrode techniques. Despite the growing application of optical mapping to cardiac electrophysiology, relatively little quantitative information is available regarding the characteristics of optical action potentials recorded from cardiac tissue. Methods and Results: A high-resolution optical mapping system and microelectrode techniques were used to determine the characteristics of guinea pig ventricular action potentials recorded with the voltage-sensitive dye di-4-ANEPPS. The effects of optical magnification, tissue-light interaction, sampling rate, voltage resolution, spatial resolution, and cardiac motion on action potential signal characteristics were determined. The optical action potential signal represents the relative change in transmembrance potential arising from a volume of cells, where the area of a recording site is determined by optical magnification and detector area, and the depth of recording is determined by system optics and the visible light transmission characteristics of cardiac muscle. Using photographic lenses, the depth of tissue contributing to the signal is 〈 250 μm. The action potential plateau and final repolarization can be accurately reconstructed from data digitized at modest sampling rates (450 to 750 Hz), since the frequency content of optical action potentials is band-limited to approximately 150 Hz. However, faster sampling rates are needed to depict the subtle details of the action potential upstroke. In addition to temporal resolution, it is essential to achieve sufficient dynamic range and voltage resolution to accurately represent the time course of membrane potential change. Voltage resolution is inversely related to the square of spatial resolution, hence, there exists an inherent trade-off between increased spatial resolution and diminished voltage resolution. Cardiac motion, which can otherwise limit spatial resolution as well as signal fidelity, can be effectively reduced using mechanical stabilization of the heart without distorting action potential characteristics. Conclusions: Optical mapping with voltage-sensitive dyes provides high-fidelity multisite action potential recording with flexible spatial resolution. When recording cardiac action potentials with voltage-sensitive dyes, the Interdependence of temporal, spatial, and voltage resolutions must be carefully considered.

Notes: Spatial Autocorrelation of APDs During Arrhythmogenic Insults. Introduction: Regional dispersions of repolarization (DOR) are arrhythmogenic perturbations that are closely associated with reentry. However, the characteristics of DOR have not been well defined or adequately analyzed because previous algorithms did not take into account spatial heterogeneities of action potential durations (APDs). Earlier simulations proposed that pathologic conditions enhance DOR by decreasing electrical coupling between cells, thereby unmasking differences in cellular repolarization between neighboring cells. Optical mapping indicated that gradients of APD and DOR are associated with fiber structure and are largely independent of activation. We developed an approach to quantitatively characterize APD gradients and DOR to determine how they are influenced by tissue anisotropy and cell coupling during diverse arrhythmogenic insults such as hypoxia and hypothermia. Methods and Results: Voltage-sensitive dyes were used to map APs from 124 sites on the epicardium of Langendorff-perfused guinea pig hearts during (1) cycles of hypoxia and reoxygenation and (2) after 30 minutes of hypothermia (32° to 25°C). We introduce an approach to quantitate DOR by analyzing two-dimensional spatial autocorrelation of APDs along directions perpendicular and parallel to the longitudinal axis of epicardial fibers. A spatial correlation length l was derived as a statistical measure of DOR. It corresponds to the distance over which APDs had comparable values, where l is inversely related to DOR. Hypoxia (30 min) caused a negligible decrease in longitudinal θL (from 0.530 ± 0.138 to 0.478 ± 0.052 m/sec) and transverse θT (from 0.225 ± 0.034 to 0.204 ± 0.021 m/sec) conduction velocities and did not alter θL/θT or activation patterns. In paced hearts (cycle length [CL] = 300 msec), hypoxia decreased APDs (123 ± 18.2 to 46 ± 0.6 msec; P 〈 0.001) within 10 to 15 minutes and enhanced DOR, as indicated by reductions of l from 1.8 ± 0.9 to 1.1 ± 0.5 mm (P 〈 0.005). Hypothermia caused marked reductions of θL, (0.53 ± 0.138 to 0.298 ± 0.104 m/sec) and θT (0.225 ± 0.034 to 0.138 ± 0.027 m/sec), increased APDs (128 ± 4.4 to 148 ± 14.5 msec), and reduced l from 2.0 ± 0.3 to 1.3 ± 0.6 mm (P 〈 0.05). l decreased with increased time of hypoxia and recovered upon reoxygenation. Hypoxia and hypothermia reduced l measured along the longitudinal (l1) and transverse (lT) axes of cardiac fibers while the ratio lL/lT remained constant.

Notes: Wavelength Adaptation and Reentry. Introduction: The stability of reentry is thought to depend on a critical balance between the spatial extent of refractory tissue in a reentrant wave (i.e., wavelength λ) and the reentrant path length. Because considerable evidence suggests that λ changes continuously in space and time during abrupt rate changes associated with the onset of tachycardia, we hypothesized that beat-by-beat adaptation of λ to the dimensions of the reentrant path plays a central role in the mechanism of initiation of reentry. Methods and Results: To investigate the dynamic relationship between λ and path length during initiation of reentry, optical mapping with voltage-sensitive dyes was used in a guinea pig model of reentrant ventricular tachycardia (VT). In this model, a computer-guided laser obstacle precisely controlled the position and dimensions of the reentrant path. Under control perfusion and after addition of 15 μ M d-sotalol, λ was monitored during steady-state pacing, premature stimulation, and the initiating beats leading to nonsustained and sustained VT. During control perfusion, reentrant VT was reproducibly induced in 8 of 8 hearts, whereas in the presence of d-sotalol, reentry could only be initiated in 1 of 8 hearts due primarily to the failure of λ to adapt to the reentrant path length. During successful initiation of VT, a consistent sequence was observed. The sequence was characterized by antidromic and orthodromic propagation around both sides of the anatomic obstacle, followed by unidirectional block of the antidromic impulse and persistence of reentry only if the λ of the orthodromic impulse adapted to the reentrant path (λ 〈 path length). d-Sotalol prevented initiation of VT by altering λ adaptation of the orthodromic wave; however, it failed to terminate ongoing VT because reverse use-dependence developed after several beats of tachycardia. Conclusion: In an experimental model where λ, path length, and cellular action potentials were monitored during initiation of reentry, we found that, in contrast to termination, the initiation of reentry and the transition from nonsustained to sustained VT is strongly dependent on beat-to-beat adaptation of λ to the dimensions of the reentrant path.

Notes: Atrial Defibrillation Thresholds. Introduction: Little investigation has been conducted to assess the atrial defibrillation thresholds of electrode configurations using electrodes designed for internal ventricular defibrillation (right ventricle [RV], superior vena cava [SVC], and pulse generator housing [Can]) combined with coronary sinus (CS) electrodes. We hypothesized that a CS → SVC+Can electrode configuration would have a lower atrial defibrillation threshold than a standard configuration for defibrillation, RV → SVC+Can. We also tested the atrial defibrillation thresholds of five other configurations. Methods and Results: In 12 closed chest sheep, we situated a two-coil (RV, SVC) defibrillation catheter, a left-pectoral subcutaneous Can, and a CS lead. Atrial fibrillation was burst induced and maintained with continuous infusion of intrapericardial acetyl-β-methylcholine chloride. Using fixed-tilt biphasic shocks, we determined the atrial defibrillation thresholds of seven test configurations in random order according to a multiple-reversal protocol. The peak voltage and delivered energy atrial defibrillation thresholds of CS → SVC+Can (168 ± 67 V, 2.68 ± 2.40 J) were significantly lower than those of RV → SVC+Can (215 ± 88 V, 4.46 ± 3.40 J). The atrial defibrillation thresholds of the other test configurations were RV+CS → SVC+Can 146 ± 59V, 1.92 ± 1.45 J; RV 
→ CS+SVC+Can:191 ± 89V, 3.53 ± 3.19 J; CS →
SVC: 188 ± 98V, 3.77 ± 4.14 J; SVC → CS+Can: 265 ±
145 V, 7.37 ± 9.12 J; and SVC → Can: 516 ± 209 V, 
24.5 ± 15.0 J. Conclusions: The atrial defibrillation threshold of CS → RV SVC+Can. In addition, the low atrial defibrillation threshold of RV+CS → SVC+Can merits further investigation. Based on corroboration of low atrial defibrillation thresholds of CS-based configurations in humans, physicians might consider using CS leads with atrioventricular defibrillators.