Different Ventricular Fibrillation (VF) Dynamics in Long QT Syndrome Type 1 vs. 2 in a Transgenic Rabbit Model

Long QT syndrome (LQTS) is a congenital disease characterized by APD prolongation and associated with sudden cardiac death. LQT1 and LQT2, the most common types of LQTS, lack delayed rectifying potassium currents, IKs and IKr, respectively. We hypothesize that the differential kinetic properties of IKs and IKr can influence vulnerability to ventricular fibrillation (VF) through genotype-specific enhancement of VF maintenance. We investigated VF dynamics in transgenic rabbit models of LQT1, LQT2, and littermate controls (LMC) with optical mapping (n=6). VF frequency (VFF) analysis showed wave propagation to be slowest in LQT2 in line with APD gradient in groups (LQT2=7.06Hz, LQT1=11.72Hz, LMC=12.14Hz). Despite low frequency in LQT2, complexity of VFs was comparable to LMC. Further pattern analysis revealed that LQT2 exhibited higher incidence of wave breaks per wave while LQT1 shows even lower than LMC (LQT2=0.374 vs. LQT1=0.234, LMC=0.320). These results highlight role of IKr vs. IKs in VF maintenance, suggesting that VFs in LQT1 and 2 are maintained by different mechanisms such as wave breaks and re-initiation of reentry vs. triggered activity.View Large Image | View Hi-Res Image | Download PowerPoint Slide