No abstract

The rat model is suitable for study of aging-related AF. Uniform partial atrial cellular uncoupling with heptanol perfusion in the young rats, although promoting inducible AT, does not mimic aging-related AF. The results suggest that heterogeneous atrial interstitial fibrosis and atrial cell hypertrophy might contribute to the aging-related increase in atrial conduction slowing, conduction block, and inducible AF in the old rat model.

Whether or not the excitation-contraction (E-C) uncoupler diacetyl monoxime (DAM) and cytochalacin D (Cyto D) alter the ventricular fibrillation (VF) activation patterns is unclear. We recorded single cell action potentials and performed optical mapping in isolated perfused swine right ventricles (RV) at different concentrations of DAM and Cyto D. Increasing the concentration of DAM results in progressively shortened action potential duration (APD) measured to 90% repolarization, reduced the slope of the APD restitition curve, decreased Kolmogorov-Sinai entropy, and reduced the number of VF wave fronts. In all RVs, 15-20 mmol/l DAM converted VF to ventricular tachycardia (VT). The VF could be reinduced after the DAM was washed out. In comparison, Cyto D (10-40 micromol/l) has no effects on APD restitution curve or the dynamics of VF. The effects of DAM on VF are associated with a reduced number of wave fronts and dynamic complexities in VF. These results are compatible with the restitution hypothesis of VF and suggest that DAM may be unsuitable as an E-C uncoupler for optical mapping studies of VF in the swine RVs.

The mechanisms are unclear. We induced sustained (Ͼ48 h) AF by rapidly pacing the left atrium (LA) in six dogs. Highdensity computerized mapping was done in the PVs and atria. Results show repetitive focal activations in all dogs and in 12 of 18 mapped PVs. Activation originated from the middle of the PV and then propagated to the LA and distal PV with conduction blocks. The right atrium (RA) was usually activated by a single large wavefront. Mean AF cycle length in the PVs (left superior, 82 Ϯ 6 ms; left inferior, 83 Ϯ 6 ms; right inferior, 83 Ϯ 4 ms) and LA posterior wall (87 Ϯ 5 ms) were significantly (P Ͻ 0.05) shorter than those in the LA anterior wall (92 Ϯ 4 ms) and RA (107 Ϯ 5 ms). PVs in normal dogs did not have focal activations during induced AF. No reentrant wavefronts were demonstrated in the PVs. We conclude that nonreentrant focal activations are present in the PVs in a canine model of pacing-induced sustained AF. arrhythmia; mapping; pacing; pathology; activation cycle length RECENT STUDIES SHOW THAT PAROXYSMAL atrial fibrillation (AF) in humans may be initiated by trains of rapid discharges from the pulmonary veins (PVs) (11) or the ligament of Marshall (LOM), which is located in the posterior wall of the left atrium (LA) (14). Our recent canine experimental study (40) demonstrated repetitive rapid activations within the LOM and the PVs in pacing-induced sustained AF, suggesting that the LOM and PVs play a role in the maintenance of this arrhythmia. However, because only a few electrodes were used to record from the PVs in that study, it was unclear if these rapid activations were due to focal discharge or microreentry. Spach et al. (33) studied human atrial tissues from patients whose ages ranged 1-70 yr. In these tissues, anisotropic propagation was necessary for a reentrant circuit to be contained within an area of 50 mm 2 . In conditions leading to obliteration of side-to-side electrical coupling between fibers (e.g., aging and chronic hypertrophy), microreentry may occur within an even smaller area (0.6 mm in width; 2.6 mm in length). These data indicate that if we were to demonstrate microreentrant circuit, a high-density electrode mapping array is necessary. Therefore, we developed a new computerized mapping system with a high-density electrode mapping array to map the detailed patterns of activation in the PVs and atria of dogs with sustained AF. The interelectrode distance was 1 mm in five dogs and 2.5 mm in one dog. Our purpose was to map PV activity during AF and relate it to possible arrhythmia mechanisms. METHODSThis research protocol was approved by the Institutional Animal Care and Use Committees and conforms to the American Heart Association Guidelines. Mongrel dogs (18-25 kg) were used in the study.Chronic pacing to induce sustained AF. Sustained AF, defined as AF that persists for 48 h off pacing, was induced by intermittent rapid pacing (40) from the LA (N ϭ 6). During the first surgery, we performed a thoracotomy via the left fourth intercostal space. A screw-in bipolar pacin...

In the heart, membrane voltage (Vm) and intracellular Ca (Cai) are bidirectionally coupled, so that ionic membrane currents regulate Cai cycling and Cai affects ionic currents regulating action potential duration (APD). Although Cai reliably and consistently tracks Vm at normal heart rates, it is possible that at very rapid rates, sarcoplasmic reticulum Cai cycling may exhibit intrinsic dynamics. Non-voltage-gated Cai release might cause local alternations in APD and refractoriness that influence wavebreak during ventricular fibrillation (VF). In this study, we tested this hypothesis by examining the extent to which Cai is associated with Vm during VF. Cai transients were mapped optically in isolated arterially perfused swine right ventricles using the fluorescent dye rhod 2 AM while intracellular membrane potential was simultaneously recorded either locally with a microelectrode (5 preparations) or globally with the voltage-sensitive dye RH-237 (5 preparations). Mutual information (MI) is a quantitative statistical measure of the extent to which knowledge of one variable (Vm) predicts the value of a second variable (Cai). MI was high during pacing and ventricular tachycardia (VT; 1.13 +/- 0.21 and 1.69 +/- 0.18, respectively) but fell dramatically during VF (0.28 +/- 0.06, P < 0.001). Cai at sites 4-6 mm apart also showed decreased MI during VF (0.63 +/- 0.13) compared with pacing (1.59 +/- 0.34, P < 0.001) or VT (2.05 +/- 0.67, P < 0.001). Spatially, Cai waves usually bore no relationship to membrane depolarization waves during nonreentrant fractionated waves typical of VF, whereas they tracked each other closely during pacing and VT. The dominant frequencies of Vm and Cai signals analyzed by fast Fourier transform were similar during VT but differed significantly during VF. Cai is closely associated with Vm closely during pacing and VT but not during VF. These findings suggest that during VF, non-voltage-gated Cai release events occur and may influence wavebreak by altering Vm and APD locally.