Physiological blocking of the mechanisms of cold death: theoretical and experimental considerations

The cold inhibited functions of skin thermoreceptors, of the thermoregulation centre, and the respiration centre during deep hypothermia can be restored without rewarming the body. The methods used were developed to lest the hypothesis that during deep hypothermia calcium ion concentration [Ca2+](i) in the cytoplasm increases. This causes a perturbation of cell metabolism, the impairment of cell membrane function that cause the inhibition of cell functioning, resulting in cell death. Such an increase in [Ca2+](i) most likely would result from an energy deficit in a deeply cooled cell, which would compromise the processes that maintain the [Ca2+](i) at about 10(-7) M. These processes require large amounts of energy since they occur against a large concentration gradient. With the use of EDTA the extracellular concentration of Ca2+ has been lowered by 15-27%, so reducing the concentration gradient for Ca2+ between the cell and the medium and in consequence facilitated the process the extrusion of cell Ca2+. During a period of cooling, sufficient to impair normal functioning, the experimental lowering of blood Ca2+ allowed the restoration of normal function without the need to rewarm. In such cases the animals survived after cooling the body to temperatures at which they would normally have succumbed. The data presented support the stated hypothesis that the impairment of cellular function in mammals by low temperatures is the result of an uncorrected rise in [Ca2+](i). (C) 2000 Published by Elsevier Science Ltd.