Effects of the chromanol 293B, a selective blocker of the slow, component of the delayed rectifier K+ current, on repolarization in human and guinea pig ventricular myocytes

Density and Kinetics of I Kr and I Ks in Guinea Pig and Rabbit Ventricular Myocytes Explain Different Efficacy of I Ks Blockade at High Heart Rate in Guinea Pig and Rabbit

“…18,19 As with chromanol 293B in guinea pig, considerable prolongation of APD remains at short cycle length. 20 The extent of APD prolongation by chromanol 293B (23% to 31%) is comparable to that reported in single ventricular myocytes of guinea pig and humans 6 but much greater than that observed in multicellular ventricular tissue preparations of guinea pig, 21 rabbit, 22 and dog. 23 Different intracellular milieus might be involved in the discrepancy.…”

“…The concentrations of chromanol 293B (10 and 30 mol/L) were comparable to that used by Bosch et al 6 Chromanol 293B blocked I Ks by 70% at 10 mol/L and by 100% at 30 mol/L, at which concentration it also blocks Ͼ50% of I to . Therefore, we used 10 mol/L chromanol 293B to assess the effects of I Ks blockade on APD.…”

“…14,[25][26][27] The evidence for the relevance of its blockade by chromanol 293B is indirect and based on the similarity of action potential prolongation in guinea pig and human ventricular myocytes at high heart rate. 6 In right ventricular myocytes isolated from explanted human hearts with primarily left heart failure, Li et al 14 demonstrated the presence of I Ks with relatively slow activation kinetics ( f of 360 ms and s of 8.5 seconds at ϩ50 mV). Recently, Virág et al 27 showed I Ks in undiseased human left ventricular myocytes with slow activation ( of 903 ms at ϩ50 mV) and relatively rapid deactivation ( of 122 ms at Ϫ40 mV).…”

“…Moreover, it prolonged APD in a frequency-independent manner in guinea pig and human ventricular myocytes. 6 This favorable characteristic of chromanol 293B may potentially have an antiarrhythmic effect on ventricular tachyarrhythmias without the harmful effect at low heart rate.…”

“…This difference is consistent with (1) the higher density of I Ks in the guinea pig and (2) its slow deactivation, which allows little time for decrease of the current during diastole. Because I Ks blocker produces APD prolongation at short cycle length in humans as in guinea pig, 6 it is suggested that I Ks is relevant in human ventricle. 14 …”