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Fedorov VV, Li L, Glukhov A, Shishkina I, Aliev RR, Mikheeva T, Nikolski VP, Rosenshtraukh LV, Efimov IR: Hibernator Citellus undulatus maintains safe cardiac conduction and is protected against tachyarrhythmias during extreme hypothermia: possible role of Cx43 and Cx45 up-regulation. Heart Rhythm. 2005 Sep;2(9):966-75.
BACKGROUND: Most mammals experience cardiac arrest during hypothermia. In contrast, hibernators remain in sinus rhythm even at body temperatures of 0 degrees C. OBJECTIVES: The purpose of this study was to quantify electrical activity and connexin expression in the heart of hibernating Siberian ground squirrel Citellus undulatus. METHODS: Optical imaging and microelectrode recordings were conducted in Langendorff-perfused hearts and isolated papillary muscles of summer active (SA, n = 19), winter hibernating (WH, n = 21), interbout arousal (IBA, n = 12), and winter active (WA, n = 3) ground squirrels and rabbits (n = 14) at temperatures from +37 degrees C to +3 degrees C. RESULTS: All studied SA and WH hearts maintained spontaneous sinus rhythm, safe propagation through the entire conduction system, and normal pattern of ventricular excitation at all temperatures. However, three of the seven IBA and all rabbit hearts lost excitability at 10 degrees C +/- 1 degrees C and 12 degrees C +/- 1 degrees C, respectively. In WH, SA, and IBA ground squirrels, temperature reduction from 37 degrees C to 3 degrees C resulted in a 10-fold slowing of ventricular conduction velocity and increased excitation threshold. At any temperature, WH ventricles had faster conduction velocity and lower excitation threshold compared with SA and IBA. Immunolabeling demonstrated that connexin43 (Cx43) was significantly up-regulated in WH and WA compared with SA myocardium: Cx43 area density was 12.4 +/- 1.3, 15.0 +/- 3.0 and 8.6 +/- 1.1 microm (2)/1,000 microm (2), respectively. Moreover, Cx45 was expressed in the WH but not in the SA or WA ventricles. CONCLUSION: Hibernator Citellus undulatus has evolved to maintain safe conduction at extreme hypothermia via up-regulation of Cx43 and Cx45 in order to protect the heart against arrhythmia associated with hypothermia. |
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