What is respiratory hypothermia?
Respiratory hypothermia — by slowly lowering the body temperature by asphyxia in a tightly sealed vessel (hypercapnic hypoxia) at a low ambient temperature, a physiological state resembling lethargy can be induced 1.
Previous attempts to rewarm deeply cooled rats were regularly unsuccessful, and it was concluded by the German physiologists that below 15°C, non-hibernating animals could not be successfully reanimated. Giaja’s Ph.D. student, Radoslav Andjus (1926-2003), was the first to reanimate a rat that was in deep hypothermia, with a colonic temperature of 0 to 2°C (Andjus, 1953). The closed vessel method of cooling animals, in which hypoxia and hypercapnia are combined, initiated an anecdote about this method introduced by Giaja 2.
This method is comprised of primary hypothermia which lowers thermogenesis (contrary to secondary, thermolytic hypothermia), along with gradual oxygen deprivation and CO2 accumulation.
In 1940, Giaja began to focus on hypothermia as a particular physiological state as his main research topic. In studying the means of inducing hypothermia, he showed that preventing (bio)chemical thermoregulation with barometric depression and low ambient temperature can cause a rat with a 15°C body temperature to exhibit a lethargic state, similar to the sleep of hibernators: slower respiration, extremely low oxygen consumption and a very slow heart rate. When the animal is rewarmed, it wakes and recovers fully. By slowly lowering the body temperature of a rat by asphyxia in a tightly sealed vessel (hypercapnic hypoxia) at a low ambient temperature, Giaja induced a physiological state resembling lethargy. The same state could be induced by direct cooling (a frigore).
However, a multitude of different methods were used to induce hypothermia, such as the application of the tremorgenic alkaloid harmine, chlorpromazine, and insulin at certain dosages. In a 1955 review, Giaja defines two kinds of hypothermia: 1) primary, where the thermogenesis is decreased, such as hypoxic, hypoxic-hypercapnic, hypercapnic, insulin- and harmine-induced hypothermia, as well as the natural lethargic state of hibernators, and 2) secondary, based on the rise of thermolysis, such as hypothermia a frigore or that induced by chlorpromazine. Giaja also describes three types of decelerated life stages in homeotherms: 1) experimental hypothermia of non-hibernators, 2) natural hypothermia of hibernators and 3) experimental hypothermia of hibernators.
A large body of his work in the later phase of his career was devoted to understanding the differences between these three states. He pointed to the case of a rat cooled to 15°C and a hibernating ground squirrel in winter sleep, both of which seemed to be in the same physiological state. However, a comparative study shows an apparent difference; the hibernator shows much lower oxygen consumption.
If the partial pressure of oxygen was decreased below 40 mmHg, the ground squirrel awakened and abruptly augmented its oxygen consumption while the rat died without any sign of body heating. The hibernator could stay in the lethargic state for weeks or even months while the rat cooled to 15°C died within 12 to 24 h. Notably, the lethargic hibernator reacted to a surgical intervention by heating to euthermia, while the non-hibernator stayed in a state of anesthesia (Giaja, 1953; Giaja and Popovic, 1953).
Giaja energetically pursued his research on procedures to induce hypothermia. In all of these studies, hypothermia by confinement (hypercapnic hypoxia or simply “Giaja’s method”) has a particular place. In The Destiny of Germans in St. Ivan and other Writings (Igic, 2002), Professor Kurt Weiss, a physiologist from Oklahoma City wrote an anecdote on the discovery of this method:
“Giaja was studying the phenomenon of hibernation in the rat. The animals were placed in wide-necked bottles, which had perforated stoppers to allow airflow while stored in a refrigerator. One day, a new technician helped with the experiments, and instead of using perforated stoppers, he inadvertently used non-perforated ones. Before long, someone noticed what the new technician had done. The “dead” rats were thrown into the container provided for carcasses, and the Professor (Giaja) was notified about the mistake. At the end of working hours when the laboratory cleaner arrived, he found living rats in some of these containers. He then reported the findings to the Professor. Afterwards, Giaja made similar experiments and concluded that hypoxia reduces thermal resistance, which—with other procedures—helps the non-hibernating mammals to survive in extremely low temperatures.”
- Ivan Djaja (Jean Giaja) and the Belgrade School of Physiology ↩
- Can outstanding research be done under less than ideal conditions? by Rajko Igić, Department of Anesthesiology and Pain Management, John H. Stroger, Jr. Hospital of Cook County, Chicago ↩