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The temperature dependence of the calcium paradox: enzymatic, functional and morphological correlates of cellular injury. J Mol Cell Cardiol 1983 Jun;15(6):393-411



Pubmed ID




Scopus ID

2-s2.0-0020512616   29 Citations


An isolated rat heart preparation was used to characterize the temperature dependence of the calcium paradox and also to assess the validity of various indices of hypothermic protection. Hearts were subjected to 10-min periods of calcium depletion at various degrees of hypothermia followed by 20 min of normothermic calcium repletion. Using enzyme or protein leakage during calcium repletion as an index of hypothermic protection during calcium depletion, paradox injury was reduced extensively by relatively moderate hypothermia. Thus, depletion at 29 degrees C reduced total creatine kinase leakage by 57 +/- 4% from 1585 +/- 24 IU/g dry wt to 677 +/- 63 IU/g dry wt and at 25 degrees C leakage was reduced by 85 +/- 4% from 1585 +/- 24 IU/g dry wt to 237 +/- 71 IU/g dry wt. However, upon calcium repletion there was no recovery of contractile function. It was not until the myocardial depletion temperature was reduced to 20 degrees C that some functional recovery occurred. Under these circumstances cumulative creatine kinase leakage was reduced to below 88 IU/g dry wt, 6% of its normothermic value and protein leakage was undetectable. Functional recovery was not complete until the temperature was reduced to 15 degrees C or below. Correlation of cumulative enzyme leakage with functional recovery suggested a narrow release threshold (50 to 100 IU/g dry wt) above which no recovery occurred and below which a full recovery could be confidently predicted. Morphological assessments an all-or-none phenomenon; thus although increasingly severe hypothermia progressively reduced the percent of cells that sustained damage (as opposed to the degree of damage in all cells), it was not until 100% of cells appeared ultrastructurally undamaged that functional recovery was observed. Calcium-free perfusion at 4 degrees C protected the intercalated discs from gross lesions and prevented the separation of the external lamina from the surface coat. Our results also stress the heterogeneity of tissue injury and hypothermic protection and in addition shed further light upon the component mechanisms contributing to calcium injury.

Author List

Baker JE, Bullock GR, Hearse DJ


John E. Baker PhD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Membrane Permeability
Cold Temperature
Coronary Disease
Creatine Kinase
Microscopy, Electron
Muscle Proteins
Myocardial Contraction
Time Factors
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a