780 15. EFFECTS OF VARIOUS FACTORS ON INHIBITION 



When a function is not directly or immediately dependent on the ATP 

 concentration, as conduction in a nerve axon, the effects of temperature 

 changes will be mainly on the functional system; in the case of the nerve 

 axon, on the rates of movements of ions across the membrane. However, 

 if one is determining the length of time required for the function to fail, 

 this will be dependent to some extent on the rates of formation and utili- 

 zation of ATP. If the temperature is raised so that the level of ATP is 

 slowly falling, the addition of an inhibitor that depresses ATP formation 

 will accelerate the decline of the function and shorten the interval before 

 the eventual failure. An inhibitor like this will thus be more effective under 

 conditions in which there is an imbalance in the high-energy metabolism, 

 and such imbalances frequently occur at abnormal temperatures. 



These miscellaneous remarks about functional inhibition are meant only 

 to supplement the more detailed discussion in Chapter 9 and to provide 

 some basis for the actual examples to be presented shortly. 



Dependence of Anoxic Effects on the Temperature 



The changes produced by hypoxia or complete anoxia of cells are basically 

 very much like those brought about by certain inhibitors that depress 

 oxidations. A good deal of study has been devoted recently to the effects 

 of anoxia at subnormal temperatures because of the use of hypothermic 

 procedures in cardiac surgery. The primary object in hypothermia is to 

 reduce the functional activities of certain tissues in order that short per- 

 iods of anoxia will not be permanently damaging. If the circulation to 

 the brain is interrupted for a period, it is postulated that the brain will 

 survive this period of anoxia better when the tissue is cooled, and the suc- 

 cess of such procedures is good evidence that this can be achieved. It has 

 also been demonstrated in animals that hypothermia reduces the central 

 nervous system damage brought about by periods of ischemia. These 

 studies have bearing on the effects of inhibition at reduced temperatures 

 and a brief discussion of some of the principles involved may not be out 

 of place. 



Actually a clear distinction must be made between the functional acti- 

 vities of a tissue and the processes that are responsible for the maintenance 

 of the integrity. In practical hypothermia the effects on brain or other 

 tissue function are not important; it is primarily a matter of the pro- 

 tection against irreversible damage to the tissue. The time element is 

 thus of major importance. When a tissue is deprived of oxygen, a sequence 

 of events occurs that is initiated by the depression of oxidative metabolism. 

 This sequence undoubtedly involves progressively a larger and larger num- 

 ber of cellular events, including electrolyte shifts, destruction of certain 

 coenzymes, changes in permeability, and dissolution of cell structure and 

 organization. At some point these processes begin to be irreversible and, 



