SEA-0400 (1 microM) significantly decreased the amplitude of early (26.6 to 14.8 mV) and delayed (12.5 to 5.9 mV) afterdepolarizations in canine heart tissue (P<0.05).
Does SEA-0400 reduce early and delayed afterdepolarizations in canine heart models?
Specific inhibition of the NCX current by SEA-0400 reduces early and delayed afterdepolarizations in canine heart models without significantly altering L-type calcium current or intracellular calcium transients, suggesting potential for abolishing triggered arrhythmias.
Absolute Event Rate: 14.8% vs 26.6%
p-value: p=<0.05
The sodium-calcium exchanger (NCX) was considered to play an important role in arrhythmogenesis under certain conditions such as heart failure or calcium overload. In the present study, the effect of SEA-0400, a selective inhibitor of the NCX, was investigated on early and delayed afterdepolarizations in canine ventricular papillary muscles and Purkinje fibres by applying conventional microelectrode techniques at 37 degrees C. The amplitude of both early and delayed afterdepolarizations was markedly decreased by 1 microM SEA-0400 from 26.6+/-2.5 to 14.8+/-1.8 mV (n=9, P<0.05) and from 12.5+/-1.7 to 5.9+/-1.4 mV (n=3, P<0.05), respectively. In enzymatically isolated canine ventricular myocytes, SEA-0400 did not change significantly the L-type calcium current and the intracellular calcium transient, studied using the whole-cell configuration of the patch-clamp technique and Fura-2 ratiometric fluorometry. It is concluded that, through the reduction of calcium overload, specific inhibition of the NCX current by SEA-0400 may abolish triggered arrhythmias.
Nagy et al. (Wed,) conducted a other in Arrhythmogenesis. SEA-0400 was evaluated on Amplitude of early afterdepolarizations (p=<0.05). SEA-0400 (1 microM) significantly decreased the amplitude of early (26.6 to 14.8 mV) and delayed (12.5 to 5.9 mV) afterdepolarizations in canine heart tissue (P<0.05).