Hibernator Citellus undulatus maintains safe cardiac conduction and is protected against tachyarrhythmias during extreme hypothermia: possible role of Cx43 and Cx45 up-regulation.
BACKGROUND
Most mammals experience cardiac arrest during hypothermia. In contrast, hibernators remain in sinus rhythm even at body temperatures of 0 degrees C.


OBJECTIVE
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.


CONCLUSIONS
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.
Fedorov
Vadim V
VV
Cardiology Research Center, Moscow, Russia.
Li
Li
L
Glukhov
Alexey
A
Shishkina
Irina
I
Aliev
Rubin R
RR
Mikheeva
Tatiana
T
Nikolski
Vladimir P
VP
Rosenshtraukh
Leonid V
LV
Efimov
Igor R
IR
D000818:Animals; D001783:Blood Flow Velocity; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D005260:Female; D006324:Heart Arrest, Induced; D006327:Heart Block / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D006329:Heart Conduction System / Q000378:metabolism* / Q000503:physiopathology; D006339:Heart Rate; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D007036:Hypothermia, Induced; D007150:Immunohistochemistry; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D012589:Sciuridae; D013610:Tachycardia / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D015854:Up-Regulation
D018031:Connexin 43; D017630:Connexins; C082920:connexin 45