title: Hypothermia-induced spatially discordant action potential duration alternans and arrhythmogenesis in nonhibernating versus hibernating mammals.
abstract: The heart of hibernating species is resistant to lethal ventricular fibrillation (VF) induced by hypothermia. Spatially discordant (SDA) cardiac alternans is a promising predictor of VF, yet its role in the mechanism of hypothermic arrhythmogenesis in both nonhibernating and hibernating mammals remains unclear. We optically mapped the posterior epicardial surface of Langendorff-perfused hearts of winter hibernating (WH, n = 13), interbout arousal (IBA; n = 4), and summer active (SA, n = 6) ground squirrels (GSs; Spermophilus undulatus) and rabbits (n = 10). Action potential duration (APD) and conduction velocity (CV) dynamic restitution and alternans were determined at 37 to 17°C. In all animals, hypothermia induced heterogeneous APD prolongation, enhanced APD dispersion, and slowed CV. In all groups, hypothermia promoted the formation of APD alternans, which was predominantly spatially concordant in GSs and SDA in rabbits (SD of APD dispersion: 4.2 ± 0.4% vs. 2.0 ± 0.3% at 37°C and 7.5 ± 1.1% vs. 3.4 ± 0.5% at 17°C, P < 0.001 for rabbits vs. the WH group, respectively). In rabbits, hypothermia significantly increased the magnitude of SDA, which enhanced the ventricular repolarization gradient, caused conduction delays (CV: 3.2 vs. 8.2 cm/s at 17°C in rabbits vs. the WH group), conduction block, and the onset of VF (0% at 37°C vs. 60% at 17°C, P < 0.01). In contrast, no arrhythmia was observed in GS hearts at any temperature. The amplitude of CV alternans was greater in rabbits (5.2 ± 0.4% versus 4.5 ± 0.3% at 37°C and 35.3 ± 4.2% vs. 14.9 ± 1.5% at 17°C in rabbits vs. the WH group, P < 0.001 at 17°C) and correlated with the amplitude of SDA. In conclusion, the mechanism underlying SDA formation during hypothermia is likely associated with CV alternans conditioned by an enhanced dispersion of repolarization. The factors of hibernating species resistance to SDA and VF seem to be the safe and dynamically stable conduction and the low dispersion of repolarization.
authors.affiliation: Laboratory of Heart Electrophysiology, Cardiology Research Center, Moscow 121552, Russia.
authors.forename: Yuriy V
authors.initials: YV
authors.lastname: Egorov
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Glukhov
authors.forename: Igor R
authors.initials: IR
authors.lastname: Efimov
authors.forename: Leonid V
authors.initials: LV
authors.lastname: Rosenshtraukh
mesh_terms: D000064:Acclimatization / Q000502:physiology; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006329:Heart Conduction System / Q000502:physiology; D006605:Hibernation / Q000502:physiology*; D007035:Hypothermia / Q000503:physiopathology*; D009200:Myocardial Contraction / Q000502:physiology*; D010210:Papillary Muscles / Q000502:physiology; D010496:Pericardium / Q000502:physiology; D011817:Rabbits / Q000502:physiology*; D012589:Sciuridae / Q000502:physiology*; D012621:Seasons; D014693:Ventricular Fibrillation / Q000503:physiopathology*; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D002118:Calcium