轻度低温通过维持缝隙连接细胞间通讯和Na+通道功能预防缺血心肌的传导障碍
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Mild hypothermia preserves myocardial conduction during ischemia by maintaining gap junction intracellular communication and Na+ channel function
背景与目的：急性心肌缺血引起的传导速度（CV）减慢和传导阻滞，触发折返性心律失常，可导致心跳骤停。我们前期在早期全心缺血的犬模型上发现轻度低温(MH,32℃）缓解了缺血导致的传导阻滞和CV减慢。假设MH可通过保存GJ表达和分布来预防缺血导致的传导阻滞和CV减慢。
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方法：将犬左心室在对照（36℃）或MH（32℃）条件下停止灌注即缺血（30min）。从透壁的左心室壁记录动作电位，并在整个缺血期间测量CV。采用共聚焦免疫荧光（IF）和/或Western blot分析检测Cx43和Na+通道（NaCh）的重塑。通过微电极记录动作电位上升速度（dV / dtmax）和静息膜电位（RMP）来分析细胞兴奋性。测量36℃和32℃时分离的犬心肌细胞的NaCh电流。
结果：MH预防了缺血30min后心肌的传导阻滞并缓解了缺血导致的CV减慢。通过IF和Western blot分析发现MH维持了闰盘（ID）处的Cx43并减弱局部缺血导致的Cx43降解。MH还保存了dV / dtmax和NaCh功能而不影响RMP。通过IF或Wb分析在ID处没有观察到NaCh表达的差异。
结论：MH通过维持ID出Cx43的表达和NaCh的功能，而预防了缺血导致的心肌传导异常。
Nassal M M, Wan X, Dale Z, et al. Mild hypothermia preserves myocardial conduction during ischemia by maintaining gap junction intracellular communication and sodium channel function.[J]. Am J Physiol Heart Circ Physiol, 2017, 312(5):H886
BACKGROUND: Acute cardiac ischemia induces conduction velocity (CV) slowing and conduction block, promoting reentrant arrhythmias leading to sudden cardiac arrest. Previously, we found that mild hypothermia (MH; 32°C) attenuates ischemia-induced conduction block and CV slowing in a canine model of early global ischemia. Acute ischemia impairs cellular excitability and the gap junction (GJ) protein connexin (Cx)43. We hypothesized that MH prevented ischemia-induced conduction block and CV slowing by preserving GJ expression and localization.
METHODS: Canine left ventricular preparations at control (36°C) or MH (32°C) were subjected to no-flow prolonged (30 min) ischemia. Optical action potentials were recorded from the transmural left ventricular wall, and CV was measured throughout ischemia. Cx43 and Na+ channel (NaCh) remodeling was assessed using both confocal immunofluorescence (IF) and/or Western blot analysis. Cellular excitability was determined by microelectrode recordings of action potential upstroke velocity (dV/dtmax) and resting membrane potential (RMP). NaCh current was measured in isolated canine myocytes at 36 and 32°C.
RESULTS:As expected, MH prevented conduction block and mitigated ischemia-induced CV slowing during 30 min of ischemia. MH maintained Cx43 at the intercalated disk (ID) and attenuated ischemia-induced Cx43 degradation by both IF and Western blot analysis. MH also preserved dV/dtmax and NaCh function without affecting RMP. No difference in NaCh expression was seen at the ID by IF or Western blot analysis.
CONCLUSIONS:In conclusion, MH preserves myocardial conduction during prolonged ischemia by maintaining Cx43 expression at the ID and maintaining NaCh function. Hypothermic preservation of GJ coupling and NaCh may be novel antiarrhythmic strategies during resuscitation.
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