SHOCK-INDUCED REFRACTORY PERIOD EXTENSION AND PHARMACOLOGICAL MODULATION OF DEFIBRILLATION THRESHOLD

Shock-induced refractory period extension (RPE) has been suggested as a mechanism of electrical defibrillation. We measured RPE caused by lo calized field stimulation measured before and during infusion of disop yramide (n = 5), flecainide (n = 5), or E-4031 (n = 5) in anesthetized dogs and determined the effect of the drugs on the internal defibrill ation threshold (DFT). In the baseline state (n = 15), 16 V/cm S2 fiel d stimulation prolonged the effective RP by 36 +/- 15 ms (22 +/- 12% o f RP without S2), whereas 4 and 8 V/cm S2 stimuli did not cause marked RPE. The RPE normalized by the RP without S2 was not significantly in fluenced by any drug (16 Vicm: disopyramide 30 +/- 11 vs. 27 +/- 11, f lecainide 25 +/- 5 vs. 19 +/- 12, and E-4031 18 +/- 13 vs. 22 +/- 14%) . Disopyramide did not alter the defibrillation threshold (4.2 +/- 0.6 -4.4 +/- 0.6 J). In 2 dogs given flecainide, ventricular fibrillation became refractory to defibrillation. In contrast, E-4031 lowered the t hreshold from 4.5 +/- 2.4 to 2.2 +/- 1.2 J (p < 0.01). The results sug gest that flecainide and E-4031 do not modulate defibrillation efficie ncy through their effects on RPE.