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Myocardial calcium overload during graded hypothermia and after rewarming in an in vivo rat model

Aim Mechanisms underlying cardiac contractile dysfunction during and after rewarming from hypothermia remain largely unknown. We have previously reported myocardial post‐hypothermic calcium overload to be the culprit. The aim of the present study was to measure changes in myocardial [Ca2+]i during g...

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Published in:Acta Physiologica 2013-03, Vol.207 (3), p.460-469
Main Authors: Wold, R. M., Kondratiev, T., Tveita, T.
Format: Article
Language:English
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Summary:Aim Mechanisms underlying cardiac contractile dysfunction during and after rewarming from hypothermia remain largely unknown. We have previously reported myocardial post‐hypothermic calcium overload to be the culprit. The aim of the present study was to measure changes in myocardial [Ca2+]i during graded hypothermia and after rewarming in an anesthetized, intact rat model, using the 45Ca2+ technique. Methods Rats were randomized and cooled to 15 °C. Hearts were excised and perfusion‐washed to remove extracellular calcium after 0.5 h of hypothermia (n = 9), 4 h of hypothermia (n = 8), and after 4 h of hypothermia and 2 h rewarming (n = 9). A normothermic group, kept at 37 °C for 5 h, served as control (n = 6). [Ca2+]i was determined in perchloric acid extracts of heart tissue. Spontaneous cardiac electromechanic work was maintained during hypothermia without cardiac arrest or ischaemia. Results Between 0.5 and 4 h at 15 °C, a six‐fold increase in cardiac [Ca2+]i was observed (0.55 ± 0.10 vs. 2.93 ± 0.76 μmol (g dry wt)−1). Rewarming resulted in a 33% decline in [Ca2+]i, but the actual value was significantly above the value measured in control hearts. Conclusion We show that calcium overload is a characteristic feature of the beating heart during deep hypothermia, which aggravates by increasing duration of exposure. The relatively low decline in [Ca2+]i during the rewarming period indicates difficulties in recovering calcium homoeostasis, which in turn may explain cardiac contractile dysfunction observed after rewarming.
ISSN:1748-1708
1748-1716
DOI:10.1111/apha.12003