MECHANISMS OF ANTIARRHYTHMIC DRUG-INDUCED CHANGES IN DEFIBRILLATION THRESHOLD - ROLE OF POTASSIUM AND SODIUM-CHANNEL CONDUCTANCE

Objectives. We sought to determine which ion current predominantly aff ects defibrillation outcomes by using specific pharmacologic probes (l idocaine [a sodium channel blocking agent] and cesium [an outward pota ssium channel blocking agent]) in 26 swine. Background. The effect of a drug on sodium or potassium channel conductance, or both, may affect defibrillation threshold values. However, it is unknown which ion cha nnel predominates. Methods. Each pig was randomly assigned to one of f our treatment groups with two treatment phases: group 1 = placebo (D5W ) in treatment phase I followed by placebo plus cesium in treatment ph ase II (n = 6); group 2 = lidocaine followed by lidocaine plus placebo (n = 7); group 3 = lidocaine followed by lidocaine plus cesium (n = 7 ); group 4 = placebo followed by placebo plus placebo (n = 6). Defibri llation threshold values and electrocardiographic measurements were ob tained at baseline and at treatment phases I and II. Results. Lidocain e increased defibrillation threshold values from baseline by 71% in gr oup 2 (p = 0.02) and by 92% in group 3 (p < 0.01). There were no chang es in defibrillation threshold values from baseline to D5W in groups 1 and 4. When D5W was added to lidocaine in group 2 and D5W in group 4, there were no significant changes in defibrillation threshold values. However, when cesium was added to lidocaine in group 3, the elevated defibrillation threshold values (mean +/- SD) returned to baseline val ues (from 15.7 +/- 3.46 to 7.55 +/- 3.19 J, p < 0.01). Cesium added to D5W in group 1 also significantly reduced defibrillation threshold va lues from 7.10 +/- 1.27 to 4.14 +/- 1.75 J (p < 0.01). The effect of c esium on defibrillation threshold values was similar between groups 1 and 3, regardless of lidocaine, such that these values were reduced by 40 +/- 14% and 51 +/- 18%, respectively (p = 0.28). Conclusions. Cesi um, through potassium blockade, reverses lidocaine-induced elevation i n defibrillation threshold values, The magnitude of defibrillation thr eshold reduction when cesium was added to lidocaine was similar to the defibrillation threshold reduction when cesium was added to placebo. Thus, inhibiting outward potassium conductance and prolonging repolari zation decreases defibrillation threshold values independent of sodium channel blockade.