Abstract
The initiation of polymorphic ventricular tachycardia in long QT syndrome type 2 (LQT2) has been associated with a characteristic ECG pattern of short-long RR intervals. We hypothesize that this characteristic pattern increases APD dispersion in LQT2, thereby promoting arrhythmia. We investigated APD dispersion and its dependence on two previous cycle lengths (CLs) in transgenic rabbit models of LQT2, LQT1, and their littermate controls (LMC) using random stimulation protocols. The results show that the short-long RR pattern was associated with a larger APD dispersion in LQT2 but not in LQT1 rabbits. The multivariate analyses of APD as a function of two previous CLs (APDn = C + α1CLn−1 + α2CLn−2) showed that α1 (APD restitution slope) is largest and heterogeneous in LQT2 but uniform in LQT1, enhancing APD dispersion under long CLn−1 in LQT2. The α2 (short-term memory) was negative in LQT2 while positive in LQT1, and the spatial pattern of α1 was inversely correlated to α2 in LQT2, which explains why a short-long combination causes a larger APD dispersion in LQT2 but not in LQT1 rabbits. In conclusion, short-long RR pattern increased APD dispersion only in LQT2 rabbits through heterogeneous APD restitution and the short-term memory, underscoring the genotype-specific triggering of arrhythmias in LQT syndrome.
Highlights
Despite the importance of APD dispersion in LQT-related arrhythmias, it is not clear whether the short-long cycle length (CL) pattern increases APD dispersion as well as how varied cycle lengths (CLs) can effect on behavior of APD dispersion
APD dispersion dynamics from littermate control (LMC), LQT1 and long QT syndrome type 2 (LQT2) rabbits were studied using randomly varying CLs and short-long CL pacing protocol and we found that APD dispersion in LQT2 rabbits is highly dependent on a previous history of heart rate variation due to heterogeneous restitution and short-term cardiac memory
When CLn−2 is larger, APD dispersion can be reduced by short-term memory effect and short CLn-2 eliminates the dampening effect by short-term memory to increase APD dispersion. These results indicate that APD dispersion is enhanced under short-long alternating cycles in LQT2 because of small short-term cardiac memory effect caused by short CLn−2
Summary
Despite the importance of APD dispersion in LQT-related arrhythmias, it is not clear whether the short-long cycle length (CL) pattern increases APD dispersion as well as how varied CL can effect on behavior of APD dispersion. Ion channel kinetics most likely underlies short-term cardiac memory and it is possible that prior heart rate variations such as short-long CL may greatly influence APD dynamics in LQTS lacking IKs or IK r and is probably an important factor in determining APD dispersion under characteristic short-long RR intervals as seen in LQT2 but not in LQT1 patients. Telemetry recordings from LQT2 rabbits showed characteristic short-long CL variation before the onset of pVT and sudden cardiac death[23,24] similar to LQT2 patients[2,3] We used these transgenic rabbits to investigate the mechanisms underlying CL–dependent APD dispersion in LQTS. APD dispersion dynamics from littermate control (LMC), LQT1 and LQT2 rabbits were studied using randomly varying CLs and short-long CL pacing protocol and we found that APD dispersion in LQT2 rabbits is highly dependent on a previous history of heart rate variation due to heterogeneous restitution and short-term cardiac memory
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
