BACKGROUND: Abnormal QT intervals, long QT or short QT, have been epidemiologically linked with sudden cardiac death because of ventricular fibrillation (VF). Consequently, Food and Drug Administration recommends testing all pharmacological agents for QT toxicity as a risk factor for cardiac toxicity. Such tests assess QT/QTc interval, which represents ventricular depolarization and repolarization. However, the current QT toxicity analysis does not account for the well-known anisotropy in cardiac tissue conductivity. Mines demonstrated in 1913 that cardiac wavelength (λ) determines inducibility of reentrant arrhythmia, where both repolarization time or action potential duration and conduction velocity determine λ=action potential duration×conduction velocity. We aimed to determine the role of anisotropic wavelength in inducibility of VF in explanted human left ventricular preparations. We tested the hypothesis that 3-dimensional cardiac wavelength, which takes into account anisotropic cardiac tissue conductivity, can accurately predict VF sustainability. METHODS: We conducted panoramic optical mapping of coronary perfused human left ventricular wedge preparations subjected to pharmacologically induced shortening and prolongation of action potential duration, by IK,ATP agonist pinacidil and antagonist glybenclamide, respectively. This measured action potential duration, conduction velocity, and thus determined pacing cycle length-dependent wavelengths in longitudinal (λL), transverse (λTV), and transmural (λTM) directions using S1S1 pacing protocol, from which wavelength volume (Vλ) was determined, as Vλ=λL×λTV×λTM, and compared with tissue volume. We tested a hypothesis that tissue volume/Vλ ratio can predict VF sustainability. RESULTS: At baseline, at pacing rate of 240 beats per minute, the wavelengths were λL=9.6±0.6 cm, λTV=4.2±0.3 cm, and λTM=5.8±0.2 cm, respectively (n=7), and thus Vλ=246.4±42.1 cm3. Administration of pinacidil at escalating concentrations progressively decreased Vλ, and VF became sustained, when tissue volume/Vλ was above safety factor κ=4.4±0.6 (n=9) during rapid pacing. Treatment with glybenclamide decreased VT/Vλ below κ at any pacing rate and prevented VF sustainability. CONCLUSIONS: Sustained VF was only sustained in ventricular volume exceeding critical Vλ=λL×λTV×λTM.
BACKGROUND: Abnormal QT intervals, long QT or short QT, have been epidemiologically linked with sudden cardiac death because of ventricular fibrillation (VF). Consequently, Food and Drug Administration recommends testing all pharmacological agents for QT toxicity as a risk factor for cardiac toxicity. Such tests assess QT/QTc interval, which represents ventricular depolarization and repolarization. However, the current QT toxicity analysis does not account for the well-known anisotropy in cardiac tissue conductivity. Mines demonstrated in 1913 that cardiac wavelength (λ) determines inducibility of reentrant arrhythmia, where both repolarization time or action potential duration and conduction velocity determine λ=action potential duration×conduction velocity. We aimed to determine the role of anisotropic wavelength in inducibility of VF in explanted human left ventricular preparations. We tested the hypothesis that 3-dimensional cardiac wavelength, which takes into account anisotropic cardiac tissue conductivity, can accurately predict VF sustainability. METHODS: We conducted panoramic optical mapping of coronary perfused human left ventricular wedge preparations subjected to pharmacologically induced shortening and prolongation of action potential duration, by IK,ATP agonist pinacidil and antagonist glybenclamide, respectively. This measured action potential duration, conduction velocity, and thus determined pacing cycle length-dependent wavelengths in longitudinal (λL), transverse (λTV), and transmural (λTM) directions using S1S1 pacing protocol, from which wavelength volume (Vλ) was determined, as Vλ=λL×λTV×λTM, and compared with tissue volume. We tested a hypothesis that tissue volume/Vλ ratio can predict VF sustainability. RESULTS: At baseline, at pacing rate of 240 beats per minute, the wavelengths were λL=9.6±0.6 cm, λTV=4.2±0.3 cm, and λTM=5.8±0.2 cm, respectively (n=7), and thus Vλ=246.4±42.1 cm3. Administration of pinacidil at escalating concentrations progressively decreased Vλ, and VF became sustained, when tissue volume/Vλ was above safety factor κ=4.4±0.6 (n=9) during rapid pacing. Treatment with glybenclamide decreased VT/Vλ below κ at any pacing rate and prevented VF sustainability. CONCLUSIONS:Sustained VF was only sustained in ventricular volume exceeding critical Vλ=λL×λTV×λTM.
Authors: Kedar Aras; Anna Gams; Ndeye Rokhaya Faye; Jaclyn Brennan; Katherine Goldrick; Jinghua Li; Yishan Zhong; Chia-Han Chiang; Elizabeth H Smith; Megan D Poston; Jacqueline Chivers; Peter Hanna; Shumpei Mori; Olujimi A Ajijola; Kalyanam Shivkumar; Donald B Hoover; Jonathan Viventi; John A Rogers; Olivier Bernus; Igor R Efimov Journal: Circ Arrhythm Electrophysiol Date: 2022-03-03
Authors: Dmitrii Smirnov; Andrey Pikunov; Roman Syunyaev; Ruslan Deviatiiarov; Oleg Gusev; Kedar Aras; Anna Gams; Aaron Koppel; Igor R Efimov Journal: PLoS One Date: 2020-05-11 Impact factor: 3.240
Authors: Elisa Ferraro; Lidia Pozhidaeva; David S Pitcher; Catherine Mansfield; Jia Han Benjamin Koh; Catherine Williamson; Oleg Aslanidi; Julia Gorelik; Fu Siong Ng Journal: Sci Rep Date: 2020-09-17 Impact factor: 4.379
Authors: Balvinder S Handa; Xinyang Li; Kedar K Aras; Norman A Qureshi; Ian Mann; Rasheda A Chowdhury; Zachary I Whinnett; Nick W F Linton; Phang Boon Lim; Prapa Kanagaratnam; Igor R Efimov; Nicholas S Peters; Fu Siong Ng Journal: Circ Arrhythm Electrophysiol Date: 2020-02-16