Chih Tai Ting

Two Types of Ventricular Fibrillation in Isolated Rabbit Hearts. Importance of Excitability and Action Potential Duration Restitution

Background—The combined effects of excitability and action potential duration (APD) restitution on wavefront dynamics remain unclear. Methods and Results—We used optical mapping techniques to study Langendorff-perfused rabbit hearts. In protocol IA (n=10), D600 at increasing concentrations was infused during ventricular fibrillation (VF). With concentration increased to 0.5 mg/L, fast VF (dominant frequency, 19.1±1.8 Hz) was consistently converted to ventricular tachycardia (VT). However, increasing D600 further to 2.5 or 5.0 mg/L converted VT to slow VF (11.9±2.3 Hz, P =0.0011). In an additional 4 hearts (protocol IB), tetrodotoxin converted a preexisting VT to slow VF (11.0±1.4 Hz). Optical maps show wandering wavelets in fast VF, organized reentry in VT, and spatiotemporal periodicity in slow VF. In protocol II, we determined APD and conduction time−1 (CT−1) restitutions during D600 infusion. CT−1 was used as an estimate of excitability. At 0.1 mg/L, APD and CT−1 restitutions were steep and flat, respectively. APD restitution became flattened when D600 increased to 0.5 mg/L, converting fast VF to VT. Further increasing D600 to 2.5 or 5.0 mg/L steepened CT−1 restitution and widened the range of S1 pacing cycle lengths over which CT−1 decreased, converting VT to slow VF. Conclusions—Two types of VF exist in isolated rabbit hearts. Fast (type I) VF is associated with a steep APD restitution, a flat CT−1 restitution, and wandering wavelets. Slow (type II) VF is associated with a flat APD restitution, a steep CT−1 restitution, and spatiotemporal periodicity. Both excitability and APD restitution are important in VF maintenance.

Pulmonary Veins and Ligament of Marshall as Sources of Rapid Activations in a Canine Model of Sustained Atrial Fibrillation

Background —In dogs, chronic rapid pacing may result in sustained atrial fibrillation (AF). However, activation patterns in pacing-induced sustained AF are unclear. Methods and Results —We induced sustained AF (>48 hours) in 6 dogs by rapid pacing for 139±84 days. We then performed computerized atrial epicardial mappings and recorded the activations in the ligament of Marshall (LOM) and the pulmonary veins (PVs). During AF, mean activation cycle length in the right atrial free wall (126±17 ms) was significantly longer than that in the left atrial free wall (96±5 ms, P =0.006). In addition, mean activation cycle length in the left atrial free wall was significantly longer than that in the LOM (84±5 ms, P <0.001), the left inferior PV (81±4 ms, P =0.001), and the left superior PV (85±7 ms, P =0.003). Similarly, the dominant frequency was highest in the LOM and the PVs (range 11.2 to 13.3 Hz), followed by the left and right atria (P <0.001). In all dogs studied, rapid and complicated electrograms were consistently observed at the LOM and the PVs. During AF, both wandering wavelets and organized reentry were present. There were more wave fronts in the left atrium than in the right atrium (P <0.001). Conclusions —In chronic pacing-induced sustained AF, the LOM and the PVs are the sources of rapid activations. The mechanism by which the left atrium activates faster and has more wave fronts than the right atrium may relate to the fact that the left atrium is closer to the sources of rapid activations.

A Tale of Two Fibrillations

Sudden cardiac death remains a major public health problem in the United States. Ventricular fibrillation (VF) is the most common arrhythmia that directly leads to sudden cardiac death. However, the mechanisms of VF are unclear. Recently,1 2 different types of VF have been demonstrated in isolated, perfused rabbit hearts linked to the electrical restitution properties of the heart (ie, the dynamic dependence of action potential duration [APD] or conduction velocity [CV] on the previous diastolic interval). Type I (fast) VF is associated with a steep APD restitution, flat CV restitution, and multiple wandering wavelets. Type II (slow) VF is associated with flat APD restitution, broad CV restitution, decreased excitability, and spatiotemporal periodicity in activation maps. Our goal in this article is to explain how this new knowledge about the 2 types of VF can account for seemingly contradictory experimental findings by different investigators, and to speculate on the relevance to patient care. In normal hearts, physiological triggers such as premature ventricular contractions (PVCs) usually do not have the ability to generate an initial wavebreak causing sustained ventricular reentry. If such an event occurs, however, practically all normal hearts can fibrillate.2 In contrast, physiological triggers can sometimes induce wavebreak, initiating reentry in diseased hearts, as a result of increased structural and electrophysiological heterogeneity caused by the disease. Wiggers et al2 reported that VF occurred in 4 distinct stages visible by cinematography. The first (tachysystolic) stage lasts no more than a few seconds, characterized by either a single spiral wave or a figure-of-eight reentry.3 A second premature stimulus given during the protective zone can terminate this reentry and prevent the induction of VF.4 The second (convulsive incoordination) stage lasts for 15 to 40 seconds. Multiple wavelets and organized reentry coexist.5,6 The third (tremulous incoordination) stage lasts …

Mother rotors and the mechanisms of D600-induced type 2 ventricular fibrillation

Background—Two types of ventricular fibrillation (VF) have been demonstrated in isolated rabbit hearts during D600 infusion. Type 1 VF is characterized by the presence of multiple, wandering wavelets, whereas type 2 VF shows local spatiotemporal periodicity. We hypothesized that a single mother rotor underlies type 2 VF. Methods and Results—One (protocol I) or 2 (protocol II) cameras were used to map the epicardial ventricular activations in Langendorff-perfused rabbit hearts. Multiple episodes of type 2 VF were induced in 22 hearts by high-concentration (≥2.5 mg/L) D600 (protocol I). During type 2 VF, a single spiral wave (n=19) and/or an epicardial breakthrough pattern (n=11) was present in 14 hearts. These spiral waves either slowly drifted or intermittently anchored on the papillary muscle (PM) of the left ventricle. Dominant-frequency (DF) analyses showed that the highest local DF was near the PM (12.5±1.1 Hz). There was an excellent correlation between the highest local DF of these spiral waves and breakthroughs (11.8±1.7 Hz) and the DF of simultaneously obtained global pseudo-ECG (11.2±1.8 Hz, r=0.97, P<0.0001) during type 2 VF. We also successfully reproduced the major features of type 2 VF by using the Luo-Rudy action-potential model in a simulated, 3-dimensional tissue slab, under conditions of reduced excitability and flat action-potential duration restitution. Conclusions—Either a stationary or a slowly drifting mother rotor can result in type 2 VF. Colocalization of the stationary mother rotors with the PM suggests the importance of underlying anatomic structures in mother rotor formation.

Progressive action potential duration shortening and the conversion from atrial flutter to atrial fibrillation in the isolated canine right atrium

OBJECTIVES We sought to evaluate the effects of progressive shortening of the action potential duration (APD) on atrial wave front stability. BACKGROUND The mechanisms of conversion from atrial flutter to atrial fibrillation (AF) are unclear. METHODS Isolated canine right atria were perfused with 1 to 5 micromol/l of acetylcholine (ACh). We mapped the endocardium by using 477 bipolar electrodes and simultaneously recorded transmembrane potentials from the epicardium. The APD(90) was measured during regular pacing (S(1)) with cycle lengths of 300 ms. Atrial arrhythmia was induced by a premature stimulus (S(2)). RESULTS At baseline, only short runs of repetitive beats (<10 cycles) were induced. After shortening the APD(90) from 124 +/- 15 ms to 72 +/- 9 ms (p < 0.01) with 1 to 2.5 micromol/l of ACh, S(2) pacing induced single, stable and stationary re-entrant wave fronts (307 +/- 277 cycles). They either anchored to pectinate muscles (5 tissues) or used pectinate muscles as part of the re-entry (4 tissues). When ACh was raised to 2.5 to 5 micromol/l, the APD(90) was further shortened to 40 +/- 12 ms (p < 0.01); S(2) pacing induced in vitro AF by two different mechanisms. In most episodes (n = 13), AF was characterized by rapid, nonstationary re-entry and multiple wave breaks. In three episodes with APD(90) <30 ms, AF was characterized by rapid, multiple, asynchronous, but stationary wave fronts. CONCLUSIONS Progressive APD shortening modulates atrial wave front stability and converts atrial flutter to AF by two mechanisms: 1) detachment of stationary re-entry from the pectinate muscle and the generation of multiple wave breaks; and 2) formation of multiple, isolated, stationary wave fronts with different activation cycle lengths.