48 PHYSIOLOGY OF INDUCED HYPOTHERMIA 



dioxide and water may be considered. Is it blocked by low temperatures to an extent 

 one would not expect from the decreased velocities of chemical reactions? 



Though slices of isolated tissues consume less oxygen with lower temperatures, 

 they do not suddenly cease consumption at any one low temperature. I interpret this 

 to mean there is no "physiological zero" above freezing at which rat tissues cease 

 to carry on oxidations. 



Some tissue homogenates and semi-purified oxidizing enzyme systems have been 

 studied at low temperatures. These also show no evidence of irreversible damage 

 within a few hours at 0° C. in their capacities to transfer oxygen (F. A. Fuhrman 

 et al, 1944). Cytochrome oxidases in particular take up oxygen with ease near 0° C. 

 While it is possible that another reaction, such as phosphorylation, will limit oxygen 

 or electron transfer at low temperature, I conclude that none has been found to do 

 so by the methods so far tried. 



Note. Two special processes cease before others when mammals are cooled, 

 namely, breathing and heart4)eating. All processes, including these, may recover 

 after an hour or two at 0° ( Andjus, Gollan, 1955 ) whether or not oxygenated blood 

 is being pumped through the tissues concerned. Are these two processes suspended 

 through failure of oxidations? For breathing, no direct answer is available; pre- 

 sumably we should ascertain whetlier oxygen is still being consumed as demanded 

 in every minute part of the reflex arcs that act in breathing. For cardiac activity 

 the evidence is decisive : oxygen is available and utilized by hearts that have reached 

 standstill or ventricular fibrillation (Hegnauer, Badeer). I conclude that synaptic 

 transmission, breathing, and pumping, the known ^•ital processes that stop at body 

 temperatures above 5° C, probably do not lack oxidative energy. My general expe- 

 rience also suggests that we rarely find under natural conditions a single limiting 

 factor, such as oxygen supply or use. controlling any process, and we would be well 

 advised to study the whole system of equilibria that shift with diminishing 

 temperature. 



SUMMARY. We have considered five stages in the delivery of oxygen to the energy- 

 yielding processes upon which cells depend for continuance of their work. In all of 

 these stages, as in oxygen consumption of the whole body, we find evidence of 

 oxygen sufficiency. Reduction of oxygen consumption in deep hypothermia is itself 

 dictated by the lessened demand for oxygen in every metabolizing cell. Cessation 

 of breathing and of heartbeats, u])on which oxygen delivery ordinarily depends, 

 itself does not arise from inability of the medulla or the heart to metabolize oxida- 

 tive energy. I conclude that cold death results from changes other than failure of 

 oxidation. V'dv from producing anoxia, therefore, hypothermia prolongs the 

 endurance of it. 



REFERENCES 



1. Adolph, E. F. : Oxygen consumption of hypothermic rats and accHmatizations to cold, 



Amer. J. Physiol. 161: 359-373, 1950. 



2. Adolph, E. F. : Some differences in responses to low temperatures hetucen warm-hloodcd 



and cold-blooded vertebrates, Amer. J. Physiol. 166:92-103, 1951. 



3. Andjus, R. K.. and Smith, A. U. ; Reanimation of adult rats from body leniprraturc^ lie- 



twecn and +2° C, J. Physiol. 12S: 446-472, 1955. 



4. P>adecr, H. : Influence of oxygen on hyi>i)tlierniic cardiac staudNtill in the iK'art-hniL; i)re])a- 



ration, Circ. Res. 3: 28-31, 1955. 



