ibernator Citellus undulatus maintains safe cardiac onduction and is protected against tachyarrhythmias uring extreme hypothermia: Possible role of Cx43 and x45 up-regulation

BACKGROUND Most mammals experience cardiac arrest during hypothermia. In contrast, hibernators remain in sinus rhythm even at body temperatures of 0°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 ϭ 19), winter hibernating (WH, n ϭ 21), interbout arousal (IBA, n ϭ 12), and winter active (WA, n ϭ 3) ground squirrels and rabbits (n ϭ 14) at temperatures from ϩ37°C to ϩ3°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°C Ϯ 1°C and 12°C Ϯ 1°C, respectively. In WH, SA, and IBA ground squirrels, temperature reduction from 37°C to 3°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 Ϯ 1.3, 15.0 Ϯ 3.0 and 8.6 Ϯ 1.1 ␮m 2 /1,000 ␮m 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.