TY - JOUR
T1 - Electrophysiological mechanisms of antiarrhythmic protection during hypothermia in winter hibernating versus nonhibernating mammals
AU - Fedorov, Vadim V.
AU - Glukhov, Alexey V.
AU - Sudharshan, Sangita
AU - Egorov, Yuri
AU - Rosenshtraukh, Leonid V.
AU - Efimov, Igor R.
N1 - Funding Information:
This work was supported by the Stanley and Lucy Lopata Endowment (Dr. Efimov), the Russian Foundation for Basic Research (grant 05-04-48311), and the Russian President Foundation for Scientific School (grant SS-6211.2006.7, Dr. Rosenshtraukh). Drs. Fedorov and Glukhov contributed equally to this work.
PY - 2008/11
Y1 - 2008/11
N2 - Background: Robust cell-to-cell coupling is critically important in the safety of cardiac conduction and protection against ventricular fibrillation (VF). Hibernating mammals have evolved naturally protective mechanisms against VF induced by hypothermia and reperfusion injury. Objective: We hypothesized that this protection strategy involves a dynamic maintenance of conduction and repolarization patterns through the improvement of gap junction functions. Methods: We optically mapped the hearts of summer-active (SA) and winter-hibernating (WH) ground squirrels Spermophilus undulatus from Siberia and nonhibernating rabbits during different temperatures (+3°C to +37°C). Results: Midhypothermia (+17°C) resulted in nonuniform conduction slowing, increased dispersion of repolarization, shortened wavelength, and consequently enhanced VF induction in SA ground squirrels and rabbits. In contrast, wavelength was increased during hypothermia in WH hearts in which VF was not inducible at any temperature. In SA and rabbit hearts, but not in WH, conduction anisotropy was significantly increased by pacing acceleration, thus promoting VF induction during hypothermia. WH hearts maintained the same rate-independent anisotropic propagation pattern even at 3°C. connexin 43 (Cx43) had more homogenous transmural distribution in WH ventricles as compared to SA. Moreover, Cx43 and N-cadherins (N-cad) densities as well as the percentage of their colocalization were significantly higher in WH compared to SA epicardium. Conclusion: Rate-independent conduction anisotropy ratio, low dispersion of repolarization, and long wavelength-these are the main electrophysiological mechanisms of antiarrhythmic protection in hibernating mammalian species during hypothermia. This strategy includes the improved gap junction function, which is due to overexpression and enhanced colocalization of Cx43 and N-cad.
AB - Background: Robust cell-to-cell coupling is critically important in the safety of cardiac conduction and protection against ventricular fibrillation (VF). Hibernating mammals have evolved naturally protective mechanisms against VF induced by hypothermia and reperfusion injury. Objective: We hypothesized that this protection strategy involves a dynamic maintenance of conduction and repolarization patterns through the improvement of gap junction functions. Methods: We optically mapped the hearts of summer-active (SA) and winter-hibernating (WH) ground squirrels Spermophilus undulatus from Siberia and nonhibernating rabbits during different temperatures (+3°C to +37°C). Results: Midhypothermia (+17°C) resulted in nonuniform conduction slowing, increased dispersion of repolarization, shortened wavelength, and consequently enhanced VF induction in SA ground squirrels and rabbits. In contrast, wavelength was increased during hypothermia in WH hearts in which VF was not inducible at any temperature. In SA and rabbit hearts, but not in WH, conduction anisotropy was significantly increased by pacing acceleration, thus promoting VF induction during hypothermia. WH hearts maintained the same rate-independent anisotropic propagation pattern even at 3°C. connexin 43 (Cx43) had more homogenous transmural distribution in WH ventricles as compared to SA. Moreover, Cx43 and N-cadherins (N-cad) densities as well as the percentage of their colocalization were significantly higher in WH compared to SA epicardium. Conclusion: Rate-independent conduction anisotropy ratio, low dispersion of repolarization, and long wavelength-these are the main electrophysiological mechanisms of antiarrhythmic protection in hibernating mammalian species during hypothermia. This strategy includes the improved gap junction function, which is due to overexpression and enhanced colocalization of Cx43 and N-cad.
KW - Conduction anisotropy
KW - Hibernation
KW - Hypothermia
KW - Optical mapping
KW - Ventricular fibrillation
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U2 - 10.1016/j.hrthm.2008.08.030
DO - 10.1016/j.hrthm.2008.08.030
M3 - Article
C2 - 18984537
AN - SCOPUS:57149147298
SN - 1547-5271
VL - 5
SP - 1587
EP - 1596
JO - Heart rhythm
JF - Heart rhythm
IS - 11
ER -