Background: Acute cardiac ischemia induces conduction velocity (CV) slowing and conduction block, promoting reentrant arrhythmias leading to sudden cardiac arrest (SCA). 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 GJ protein connexin 43 (Cx43). We hypothesized that MH prevented ischemia-induced conduction block and CV slowing by preserving GJ expression and localization. Methods and Results: Canine left ventricle preparations at control (CT, 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 sodium channel (NaCh) remodeling was assessed using both confocal immunofluorescence (IF) and/or western blot. Cellular excitability was determined by microelectrode recordings of action potential upstroke velocity (dV/dTmax), and resting membrane potential (RMP). INa was measured in isolated canine myocytes at 36°C and 32°C. As expected, MH prevented conduction block and mitigated ischemia-induced CV slowing during 30 minutes of ischemia. MH maintained Cx43 at the intercalated disk (ID) and attenuated ischemia-induced Cx43 degradation by both IF and western blot. MH also preserved dV/dTmax and NaCh function without affecting RMP. No difference in NaCh expression was seen at the ID by Western blot or IF. Conclusions: 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.
- ventricular fibrillation
- connexin 43
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology