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Multiomics analysis of canine myocardium after circumferential pulmonary vein ablation: Effect of NPY on long-term reinduction of atrial fibrillation

ABSTRACT: In this study,We established a long-term model of beagle canines after circumferential pulmonary vein ablation (CPVA). The transcriptome and proteome were obtained using high-throughput sequencing and TMT-tagged LC‒MS/LC analysis. Differentially expressed genes and proteins were screened and enriched, and the effect of fibrosis was found and verified in tissues

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE248285 | GEO | 2024/08/14

REPOSITORIES: GEO

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Project description:BackgroundAbnormal 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.MethodsWe 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.ResultsAt 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.ConclusionsSustained VF was only sustained in ventricular volume exceeding critical Vλ=λL×λTV×λTM.

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Multiomics analysis of canine myocardium after circumferential pulmonary vein ablation: Effect of NPY on long-term reinduction of atrial fibrillation

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