title: Myocardial calcium overload during graded hypothermia and after rewarming in an in vivo rat model.
abstract: OBJECTIVE
  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 [Ca(2+) ](i) during graded hypothermia and after rewarming in an anesthetized, intact rat model, using the (45) Ca(2+) 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). [Ca(2+) ](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 [Ca(2+) ](i) was observed (0.55 ± 0.10 vs. 2.93 ± 0.76 μmol (g dry wt)(-1) ). Rewarming resulted in a 33% decline in [Ca(2+) ](i) , but the actual value was significantly above the value measured in control hearts.
  
  
  CONCLUSIONS
  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 [Ca(2+) ](i) during the rewarming period indicates difficulties in recovering calcium homoeostasis, which in turn may explain cardiac contractile dysfunction observed after rewarming.
authors.affiliation: Anaesthesia and Critical Care Research group, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway. ragn-hild.m.wold@uit.no
authors.forename: R M
authors.initials: RM
authors.lastname: Wold
authors.forename: T
authors.initials: T
authors.lastname: Kondratiev
authors.forename: T
authors.initials: T
authors.lastname: Tveita
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D004195:Disease Models, Animal; D007036:Hypothermia, Induced / Q000009:adverse effects*; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017694:Rewarming / Q000009:adverse effects*; D013318:Stroke Volume; D013997:Time Factors; D015854:Up-Regulation; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
chemical_list: D002132:Calcium Radioisotopes; D002118:Calcium