{'fraction_non_alphanumeric': 0.048879837067209775, 'fraction_numerical': 0.02189409368635438, 'mean_word_length': 5.55, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Rewarming Shock Disrupts Intracellular Ca2+ Homeostasis and Contractility in Cardiomyocytes

Hypothermia/Rewarming (H/R) induces myocardial dysfunction although the underlying intracellular mechanisms remain elusive. We hypothesized that in cardiomyocytes, H/R disrupts intracellular Ca2+ ([Ca2+]cyt) homeostasis via an effect on both release and clearance of cytosolic Ca2+ leading to a prolongation of evoked [Ca2+]cyt transients associated with activation with downstream impact on contractility. To test this hypothesis, isolated rat cardiomyocytes (13–15 cells from 6 rats per group) were loaded with the Ca2+ indicator, Fura‐2AM (0.5 μM), and exposed to H/R with or without electrical pacing at 0.5 Hz. In both groups, evoked [Ca2+]cyt and contractile (sarcomere length (SL) shortening) responses were simultaneously measured at 35°C before and after hypothermia using an IonOptix system. H/R experiments were conducted as follows: experimental temperature was cooled from 35°C to 15°C in 30 min, maintained at 15°C for 2 h, and then rewarmed back to 35°C in 30 min. Time‐matched controls were implemented for 3 h at 35°C. With electrical pacing throughout hypothermia, basal [Ca2+]cyt increased and the kinetics of the evoked [Ca2+]cyt responses were prolonged. In addition, the extent and velocity of SL shortening was reduced in cardiomyocytes that were paced during hypothermia. In contrast, in cardiomyocytes that were not electrically paced during hypothermia, basal [Ca2+]cyt was maintained and the kinetics of evoked [Ca2+]cyt transients were unaffected. In addition, in the absence of pacing during hypothermia, contractility of cardiomyocytes was unaffected. These results suggest that H/R affects the release and clearance of evoked [Ca2+]cyt transients (e.g., RyR mediated Ca2+ release and SERCA mediated clearance) such that basal [Ca2+]cyt increases. This effect of H/R on [Ca2+]cyt homeostasis is associated with reduced cardiac contractility.