Fedorov Vadim V, Glukhov Alexey V, Sudharshan Sangita, Egorov Yuri, Rosenshtraukh Leonid V, Efimov Igor R
Department of Biomedical Engineering, Washington University, St. Louis, Missouri 63130-4899, USA.
Heart Rhythm. 2008 Nov;5(11):1587-96. doi: 10.1016/j.hrthm.2008.08.030. Epub 2008 Aug 31.
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.
We hypothesized that this protection strategy involves a dynamic maintenance of conduction and repolarization patterns through the improvement of gap junction functions.
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 degrees C to +37 degrees C).
Midhypothermia (+17 degrees 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 degrees 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.
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.
强大的细胞间偶联对于心脏传导安全及预防心室颤动（VF）至关重要。冬眠哺乳动物已进化出针对低温及再灌注损伤诱导的VF的天然保护机制。
我们推测这种保护策略涉及通过改善缝隙连接功能动态维持传导和复极模式。
我们在不同温度（+3℃至+37℃）下对来自西伯利亚的夏季活跃（SA）和冬季冬眠（WH）的草原土拨鼠（黄鼠属）以及非冬眠兔子的心脏进行光学标测。
中度低温（+17℃）导致SA草原土拨鼠和兔子的传导不均匀减慢、复极离散增加、波长缩短，进而增强VF诱导。相比之下，低温期间WH心脏的波长增加，在任何温度下均未诱发VF。在SA和兔子心脏中，但不是在WH心脏中，起搏加速会显著增加传导各向异性，从而在低温期间促进VF诱导。即使在3℃时，WH心脏也保持相同的速率无关各向异性传播模式。与SA相比，连接蛋白43（Cx43）在WH心室中的跨壁分布更均匀。此外，与SA心外膜相比，WH心外膜中Cx43和N-钙黏蛋白（N-cad）的密度以及它们共定位的百分比显著更高。
速率无关的传导各向异性比率、低复极离散和长波长——这些是冬眠哺乳动物在低温期间抗心律失常保护的主要电生理机制。这种策略包括改善缝隙连接功能，这是由于Cx43和N-cad的过表达和增强的共定位所致。
