Depressed Metabolism

This is the fifth entry in a series about resuscitation of non-hibernating rodents from circulatory arrest at ultraprofound hypothermic and high subzero temperatures. As we have seen, Radoslav Andjus had determined a method for achieving excellent (75-100%) recovery rates in rats cooled to 0-2 degrees C by local cardiac heating prior to warming the whole body during resuscitation. The basic assumption was that it was necessary to keep oxygen demands in the body at a low level until the heart was able to supply oxygenated blood to the tissues.

However, in simultaneous experiments, Audrey Smith quickly found that hamsters appeared to require whole body warming for resuscitation from ultraprofound hypothermic temperatures. In fact, no hamsters were revived using the local cardiac heating technique, which prompted Smith to question whether it was really necessary for resuscitating rats and other non-hibernating mammals. As usual, the answer to this question was to be determined through experimentation, this time in collaboration with S.A. Goldzveig in 1955 (results were published in the Journal of Physiology in January 1956).

Goldzveig and Smith first replicated previous experiments by cooling 104 rats (150-190 g) to between 0.1 and 1.2 degrees C and attempting resuscitation using local cardiac heating with microwave diathermy. Of these rats, 78 were long-term survivors.

Whole body warming was initially carried out on 12 rats using three 100W bench lamps. The rat was placed supine on a wire grid and two lamps were placed as close as possible to the ventral surface and a third beneath the dorsal surface of the body. Three rats resumed breathing but died soon afterward. The authors reported that “the appearance of the skin suggested that the animals had been overheated.”

So they tried again. This time they placed the two 100 W ventral bench lamps further away, leaving an air gap 5-8 cm from the body. The third lamp was reduced to 60 W and also placed 5-8 cm from the dorsal surface of the body. All twelve of these animals recovered completely, suggesting that the position of the lamps was paramount to recovery. Thinking that intensity of illumination might also be of importance, they played with reducing illumination further: 4 of 6 rats rewarmed using one 40 W and two 100 W lamps recovered completely, but further reductions in illumination did not produce better results. In general, rats resuscitated by local cardiac heating began breathing spontaneously much earlier (within 11-15 minutes) than rats resuscitated by heating the whole body (14-23 minutes), but no other differences in rats recovered by the two methods were observed.

Mice (22-38.5 g) of two different strains (one of which was susceptible to bacterial hepatitis) were used for further cooling experiments. They were cooled in the same manner as rats, but due to having much less body mass they cooled much more rapidly. They ceased breathing between 4.5 and 5 degrees C, and the heart stopped beating between 2.5 and 3.8 degrees C. Mice were left in ice for 55-60 minutes after respiration and heartbeat had stopped.

Two methods of resuscitation of ice-cold mice were attempted. Nine of eleven mice were long-time survivors of local cardiac heating by microwave diathermy (intensity of the microwave was reduced to account for smaller body mass). The first attempt at recovering mice by whole-body illumination under a 60 W bench lamp resulted in a 100% recovery rate, but was followed by 10 delayed deaths at 3 weeks, which upon necropsy were found to be due to fulminating hepatitis. The experiment was repeated using another strain of mice, of which all recovered fully and 19 of the 21 were long-term survivors.

These experiments proved that local cardiac heating is not necessary for complete recovery of adults rats and mice from ultraprofound hypothermic temperature, and, almost as importantly, that a simple bench lamp was as effective as a microwave magnetron in recovering animals from this state of “suspended animation.” Goldzveig and Smith admitted that even these results could probably be improved upon by further manipulation of variables, but stressed that “…from a theoretical point of view, these results are of great importance and suggest that the danger of tissue anoxia has been exaggerated.”