HYPOTHERMIA AND BACTERIAL TOXINS 



The first experiment indicated a significantly prolonged survival 

 time and milder tetanic manifestations in hypothermic mice. These 

 mice, however, got more pronounced tetanus and died at or very 

 soon after rewarming. To this result, which may mean simply that 

 a postponement of the toxic effect has come to an end, may be con- 

 tributed the trauma induced by the rewarming process itself. The 

 possibility also remains that warming up effects a compensatory 

 overnormal metabolism, thus giving the toxin an especially good 

 access to susceptible cells. 



If the protective effect of hypothermia is due to a retarded 

 fixation of the toxin to its receptor cells, hypothermia should pro- 

 long the period during which the toxin may be neutralized by anti- 

 toxin before its entry into these cells. Too few experiments have 

 been made to allow a safe verification of this assumption, but it is 

 interesting to note that with a toxin- antitoxin interval of four hours, 

 a two hour period of hypothermia increased the average survival 

 to not less than 37 hours. Further experiments are planned to in- 

 vestigate whether this increase may be converted to a lasting sur- 

 vival if an adequate toxin- antitoxin interval is chosen. 



The evaluation of these results with tetanus toxin must be made 

 with great caution. The injection of toxin was made subcutaneously 

 and though hypothermia did not start until about 2 hours after the 

 injection, part of the toxin may have been more slowly absorbed in 

 hypothermic animals. Furthermore, narcotics, as a rule, have an 

 attenuating effect on tetanic manifestations. There are good reasons 

 to believe that the drugs given as pretreatment are more slowly 

 eliminated in hypothermic animals, and this may account for at 

 least part of the protective effect of hypothermia. Therefore, 

 staphylococcal toxin was chosen for the subsequent tests. In this 

 case the situation is apparently reversed, in that the effect of this 

 toxin seems to be enhanced by the narcotics used for pretreatment. 



Hypothermia was also found to prolong the survival time after 

 the injection of staphylococcal toxin. On the basis of the same con- 

 siderations as for tetanus toxin, a series of neutralization tests have 

 been begun which have already indicated a fairly good correlation 

 between the time allowed to pass between the injections of toxin and 

 antitoxin, and the ability of antitoxin to prolong the survival time in 



145 



