TY - JOUR
T1 - Hibernator Citellus undulatus maintains safe cardiac conduction and is protected against tachyarrhythmias during extreme hypothermia
T2 - Possible role of Cx43 and Cx45 up-regulation
AU - Fedorov, Vadim V.
AU - Li, Li
AU - Glukhov, Alexey
AU - Shishkina, Irina
AU - Aliev, Rubin R.
AU - Mikheeva, Tatiana
AU - Nikolski, Vladimir P.
AU - Rosenshtraukh, Leonid V.
AU - Efimov, Igor R.
N1 - Funding Information:
The project was supported by the Elmer L. Lindseth Endowment (Case Western Reserve University), the Stanley and Lucy Lopata Endowment (Washington University), Russian Foundation for Basic Research Grant 05-04-48311, and Russian President Foundation for Scientific School Grant SS-1535.2003.4 (Cardiology Research Center).
PY - 2005/9
Y1 - 2005/9
N2 - 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 = 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°C to + 3°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 ± 1°C and 12°C ± 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 ± 1.3, 15.0 ± 3.0 and 8.6 ± 1.1 μm2/1,000 μm2, 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.
AB - 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 = 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°C to + 3°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 ± 1°C and 12°C ± 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 ± 1.3, 15.0 ± 3.0 and 8.6 ± 1.1 μm2/1,000 μm2, 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.
KW - Conduction velocity
KW - Connexin
KW - Hibernation
KW - Hypothermia
KW - Immunohistochemistry
KW - Optical mapping
KW - Ventricular fibrillation
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U2 - 10.1016/j.hrthm.2005.06.012
DO - 10.1016/j.hrthm.2005.06.012
M3 - Article
C2 - 16171752
AN - SCOPUS:25444501499
SN - 1547-5271
VL - 2
SP - 966
EP - 975
JO - Heart rhythm
JF - Heart rhythm
IS - 9
ER -