JAMES A. MILLER, JR. 233 



upon adult organisms. These are reviewed perennially in the Annual Review 

 of Physiology. For many aspects of the subject not covered here the 

 interested reader is directed to chapters entitled 'Temperature Regulation' 

 or 'Heat and Cold' in the following volumes: 1 (1939), 3 (1941), 5 (1943), 

 6 (1944), 7 (1945), 10 (1948), 12 (1950), 13 (1951), 14 (1952), 17 (1955). 

 A more extended discussion of many aspects of the applications of hypo- 

 thermic physiology to surgery may be found in Virtue's book (182). 



The sharp distincion between the primary and secondary effects of 

 hypothermia must be emphasized. That temperature elevation increases 

 and depression decreases rates of activity has long been recognized for 

 poikilothermic animals, plants, unicellular organisms, and for chemical and 

 physical phenomena in general. This primary effect has sometimes been 

 overlooked in studies on adult mammals, in which the secondary effects 

 resulting from homeostatic mechanisms are so prominent. However, these 

 phenomena are not involved in the case of isolated mammalian organs or 

 tissues. Very small fragments of organs can be cultured in suitable 

 nutrient medium at normal body temperature, but the only method of 

 maintaining the vitality of relatively large masses of tissues or organs is 

 by the use of hypothermia to reduce metabolic requirements. In recent 

 years it has been found that the vitality of tissues and even organs can 

 be preserved for long periods at the temperature of carbon dioxide ice 

 (see below). Since, however, it appears unlikely that intact higher 

 organisms can be so preserved, our present interest is limited to tem- 

 peratures above the freezing point of water. For all adult organs studied 

 the optimal temperature for maintenance of viable tissues has been found 

 to be between 5° and 0°C. Examples of organs which have been kept 

 viable for long periods at these temperatures include skin (42, 19, 143 et al.) , 

 blood vessels (145), corneas (28, 160, and others), and entire frog eyes 

 (174). 



Certain pertinent aspects of the responses of intact animals to low 

 temperature are discussed below. 



Metabolism. The fundamental and most important effect of hypothermia 

 is its influence ui:)on metabolism. In mammals as well as in poikilothermic 

 organisms cooling produces a progressive reduction in rate of vital proc- 

 esses in accordance with van't Hoff's law. In the conscious adult mammal 

 reduction of core temperature is resisted by homeostatic mechanisms which 

 raise metabolism about 200-400% (32). Likewise, in newborn guinea pigs 

 we have found increases up to 241% during shivering. When homeostatic 

 mechanisms are blocked by narcosis, and/or ganglioplegic drugs, or by 

 asphyxia, a smooth fall in body temperature with corresponding fall 

 in overall metabolism can be achieved even in adults (32, 59). Bigelow 

 found the metabolism of a dog reduced to 55% at 28°C, 39% at 25°C and 



