Role of sodium channels in ventricular fibrillation: A study in nonischemic isolated hearts

Because the role of sodium channels in the initiation and maintenance of VF is not fully elucidated, we studied the significance of sodium channel act ivity in VF using sodium channel blockers. In nonischemic isolated feline h earts, the following electrophysiologic parameters were measured before and after application of tetrodotoxin (5 x 10(-7) M, n = 6) or lidocaine (1 x 10(-5) M, n = 8): (a) during pacing, epicardial conduction time; refractori ness; the fastest rate for 1:1 pacing/ response capture, and all tissue res istivity, indirectly reflecting intercellular electrical resistance; (b) du ring 8 min of electrically induced tachyarrhythmias, all tissue resistivity ; peak frequency (to measure average frequency based on fast-Fourier transf ormation analysis); and normalized entropy (to measure the degree of arrhyt hmia organization). In nonischemic isolated rabbit hearts (n = 4), three-di mensional mapping was performed before and after application of lidocaine ( 1 x 10-5 M). In feline hearts, lidocaine and tetrodotoxin application resul ted in: (a) more spontaneous arrhythmia termination (63-67%) than in nontre ated hearts (7%); (b) transformation from mainly VF into ventricular tachyc ardia with increased organization; and (c) prolongation of conduction time (155-248%) (p < 0.01 for all parameters). The ventricular refractory period was slightly prolonged by tetrodotoxin in the right ventricle and exhibite d rate-dependent shortening in control and with lidocaine. Tetrodotoxin and lidocaine reduced the pacing rate for 1:1 pacing/response capture, and all tissue resistivity was not significantly affected. Peak frequency was decr eased by tetrodotoxin and lidocaine mainly in the left ventricle (p < 0.01) . In nontreated left ventricles, peak frequency was increased over time but was attenuated by lidocaine. In isolated rabbit hearts, several simultaneo us wave fronts were detected during VF in nontreated hearts and were reduce d to only one or two major wavefronts after application of lidocaine. Suppr ession of sodium channel activity that primarily slowed conduction time and had little or no effect on ventricular refractory period and all tissue re sistivity resulted in less stable and more organized arrhythmias and reduce d tachyarrhythmia rate compared with nontreated hearts. These results sugge st an active role for sodium channels in the maintenance of ventricular fib rillation.