Short-Long Heart Rate Variation Increases Dispersion of Action Potential Duration in Long QT Type 2 Transgenic Rabbit Model

Tae Yun Kim, Paul Jeng, Jung Min Hwang, Zachary Pfeiffer, Divyang Patel, Leroy L. Cooper, Konstantinos Kossidas, Jason Centracchio, Xuwen Peng, Gideon Koren, Zhilin Qu, Bum Rak Choi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number14849
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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pamidronate
Long QT Syndrome
Action Potentials
Heart Rate
Rabbits
Short-Term Memory
Cardiac Arrhythmias

All Science Journal Classification (ASJC) codes

  • General

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Kim, Tae Yun ; Jeng, Paul ; Hwang, Jung Min ; Pfeiffer, Zachary ; Patel, Divyang ; Cooper, Leroy L. ; Kossidas, Konstantinos ; Centracchio, Jason ; Peng, Xuwen ; Koren, Gideon ; Qu, Zhilin ; Choi, Bum Rak. / Short-Long Heart Rate Variation Increases Dispersion of Action Potential Duration in Long QT Type 2 Transgenic Rabbit Model. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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title = "Short-Long Heart Rate Variation Increases Dispersion of Action Potential Duration in Long QT Type 2 Transgenic Rabbit Model",
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.",
author = "Kim, {Tae Yun} and Paul Jeng and Hwang, {Jung Min} and Zachary Pfeiffer and Divyang Patel and Cooper, {Leroy L.} and Konstantinos Kossidas and Jason Centracchio and Xuwen Peng and Gideon Koren and Zhilin Qu and Choi, {Bum Rak}",
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Kim, TY, Jeng, P, Hwang, JM, Pfeiffer, Z, Patel, D, Cooper, LL, Kossidas, K, Centracchio, J, Peng, X, Koren, G, Qu, Z & Choi, BR 2019, 'Short-Long Heart Rate Variation Increases Dispersion of Action Potential Duration in Long QT Type 2 Transgenic Rabbit Model', Scientific reports, vol. 9, no. 1, 14849. https://doi.org/10.1038/s41598-019-51230-9

Short-Long Heart Rate Variation Increases Dispersion of Action Potential Duration in Long QT Type 2 Transgenic Rabbit Model. / Kim, Tae Yun; Jeng, Paul; Hwang, Jung Min; Pfeiffer, Zachary; Patel, Divyang; Cooper, Leroy L.; Kossidas, Konstantinos; Centracchio, Jason; Peng, Xuwen; Koren, Gideon; Qu, Zhilin; Choi, Bum Rak.

In: Scientific reports, Vol. 9, No. 1, 14849, 01.12.2019.

Research output: Contribution to journalArticle

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T1 - Short-Long Heart Rate Variation Increases Dispersion of Action Potential Duration in Long QT Type 2 Transgenic Rabbit Model

AU - Kim, Tae Yun

AU - Jeng, Paul

AU - Hwang, Jung Min

AU - Pfeiffer, Zachary

AU - Patel, Divyang

AU - Cooper, Leroy L.

AU - Kossidas, Konstantinos

AU - Centracchio, Jason

AU - Peng, Xuwen

AU - Koren, Gideon

AU - Qu, Zhilin

AU - Choi, Bum Rak

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

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