ryanodine receptor (RyR) dysfunction. 16-18 Given clinical observations of increased ventricular ectopy and irritability during SH, frequent triggered arrhythmias would be predicted. 10,19,20 Moreover, although repolarization abnormalities induced by hypothermia are known to promote substrates for re-entrant VF, 21 the effect of hypothermia on VF triggers is poorly understood.Despite the contrast in arrhythmia susceptibility associated with TH vs. SH, there have been very few systematic studies that have investigated the underlying arrhythmia mechanisms. Existing data on the effect of hypothermia on Ca dysregulation and triggered activity is difficult to interpret because many studies have been performed at temperatures even colder than those observed during SH (e.g., room temperature) and in varied species. 22,23 Moreover, the effect of hypothermia on cellular Ca regulation is complex, such that the net impact on susceptibility to arrhythmias is difficult to predict. Therefore, we aimed to investigate the effects of clinically relevant temperatures on Ca dysregulation and triggered arrhythmias in a single animal model at the tissue, cellular and subcellular level. We hypothesized T herapeutic hypothermia (TH) improves neurologic outcomes and survival in patients with return of spontaneous circulation (ROSC) after cardiac arrest. 1,2 Current cardiopulmonary resuscitation guidelines recommend that all comatose patients with ROSC should be cooled to have temperature maintained between 32 and 36°C for 24 h. 3-6 In addition to improving neurological outcomes, several recent experimental and clinical studies 7-9 suggest that TH decreases infarct size in acute myocardial infarction. Importantly, the incidence of lethal arrhythmias in post-resuscitated patients treated with TH is relatively low, 1,4,10 suggesting that temperatures used in clinical TH may be antiarrhythmic, although this is controversial. 11- 13 Unlike TH, severe hypothermia (SH, less than 30°C), is well known to be pro-arrhythmic. Arrhythmias in patients with accidental SH are common and include ventricular fibrillation (VF), which can be refractory to standard therapy. 14,15 Experimental studies have shown that hypothermia causes dysregulation of cellular calcium (Ca), which has been associated with intracellular Ca overload and Background: Severe hypothermia (SH) is known to be arrhythmogenic, but the effect of therapeutic hypothermia (TH) on arrhythmias is unclear. It is hypothesized that susceptibility to Ca-mediated arrhythmia triggers would be increased only by SH.