Metabolism, we know, is the basis of all the organism’s vital activity. The gravity of its disorders during terminal states determines, in the long run, both the degree and the reversibility of the functional and morphological changes taking place in the organism.
One of the main pathogenetic factors in terminal states is hypoxia, which disturbs metabolism in all tissues and has a particularly severe effect on the central nervous system, the organ most sensitive to oxygen starvation. The subsequent possibility of restoring it, and also the organism as a whole, depends on the severity of this damage.
As noted above, oxygen starvation during the extinction of vital functions causes the organism to gradually shift from oxidative to the glycolytic way of utilizing carbohydrates. The latter method of obtaining energy is not economic, the same quantity of substrate yielding 15 to 20 times less energy. The shift to glycolysis during terminal states rapidly exhausts the glucose, glycogen, and other sources of energy in the tissues.
Laboratory experiments have shown that even before the approach of agony, but especially during it, the glucose, ATP, and phosphocreatine content of the brain tissue drops considerably, whereas inorganic phosphorus and lactic acid contents increase. The deep changes of phospho-carbohydrate metabolism in the brain disturb metabolism of protein and of other compounds linked with the structural elements of nerve tissue. Determination of nitrogen-containing compounds shows that the amount of easily hydrolysed amino groups of protein and bound amino groups in brain tissue drops during dying, while the ammonia content increases.
The anaerobic glycolytic path of utilizing carbohydrates, typical of terminal states, and especially of clinical death, causes acid metabolites to accumulate in the organism, and brings on the development of uncompensated metabolic acidosis. Toward the beginning of agony the total content of organic acids in the blood rises approximately 50 per cent.
In carrying out reanimation measures, in particular artificial respiration and restoration of circulation, arterial blood is rapidly oxygenated. Within a minute of the beginning of artificial ventilation the oxygen saturation of blood is already in most cases close to its original value. It must be noted, however, that the oxygen utilization by the whole organism differs considerably during this period from that of the brain tissue.
Whereas the ability of most tissues to utilize oxygen is rapidly restored, and total oxygen utilization is even increased against the initial level 5 to 25 minutes after the beginning of reanimation, it is lowered in the brain right after resuscitation, despite abundant perfusion of the brain. An increase of cardiac minute volume, high saturation of the blood with oxygen, and easier transfer of oxygen to tissues owing to a favourable change in oxyhaemoglobin dissociation promote the considerable increase in the organism’s total oxygen consumption.
In spite of the factors mentioned above, however, which tend to eliminate the results of the extremely severe anoxia, sustained by the organism, the disturbances of metabolism are observed after reanimation for many hours, or even days. After cardiac activity has been restored as a result of washing incompletely oxidized metabolites out of the tissues into the blood, metabolic acidosis increases, reaching a maximum five or ten minutes after the beginning of reanimation, which coincides in time with the restoration of respiration.
The total content of organic acids is two or three times higher than the initial, and the lactic acid content four times higher, while the lactate/pyruvate ratio increases to 45. Compensation of metabolic acidosis begins 90 minutes to three hours after the commencement of resuscitation measures independently of the cause of circulatory arrest. Compensated or subcompensated changes in acid-base equilibrium last much longer.
Experimental study of changes in acid-base equilibrium during terminal states of various origin has shown that they take place in two phases. The first phase is specific and depends on the cause of the given terminal state. It begins during dying and ends in the first two or twelve minutes of the postreanimation period. The disturbances of acid-base equilibrium during it vary in nature, and mainly depend on the character of respiration during dying. During dying from asphyxia, mixed acidosis (gaseous and metabolic) is observed. In cases of blood loss, electric shock and heart tamponade metabolic acidosis is combined with gaseous alkalosis in arterial blood owing to the development of compensatory panting.
In the second phase the changes become of the same type for all forms of dying and are due to the results of the extremely severe hypoxia. Three or four hours after the beginning of resuscitation after compensation of metabolic acidosis, gaseous alkalosis gradually develops; blood pH rises above the original figure and blood pCO2 drops. At the same time several metabolic indices, while not reaching normal values, come close to them than those observed during the first hour after reanimation.
There is a considerable fall in the blood content of incompletely oxidized products; oxidative metabolism is completely restored in the brain tissue, and the phosphocreatine content is not only restored to the initial level, but even exceeds it, while the content of inorganic phosphorus is sharply lowered. This relative normalization of metabolism, however, is temporary and disturbances subsequently reappear.
In the late restorative period gaseous alkalosis is accompanied with other disturbances of metabolism. Secondary hypoxia often develops nine to twelve hours after reanimation and the content of organic acids in the blood increases again and not only exceeds the initial level, but even that of the period between three and six hours after reanimation. The content of lactic and pyruvic acids, on the other hand, drops below the original value.
Whereas the lactic acid content in the initial state was around 20 per cent of the total amount of organic acids, from three hours after reanimation up to the end of the first 24 hours it drops to 10 per cent. Even when restoration of functions begins rapidly in animals after clinical death, as judged by their appearance and behaviour, disorders of metabolism are still observed several days after resuscitation. The presence of incompletely oxidized metabolites and the resultant decrease in the blood’s capacity to bind carbon dioxide apparently induce loss of CO2 from the blood and consequently the development of gaseous alkalosis.
Evidence that gaseous alkalosis develops in the postreanimation period as a compensatory reaction to metabolic acidosis was obtained from experiments on healthy dogs, in which acidosis was induced by injecting lactic acid. Compensation of the acidosis sets in these animals at approximately the same time as for the dogs that had survived clinical death, and with them, too, blood pH considerably exceeded the original level for several hours.
The sharp fluctuations of acid-base equilibrium and a rapid shift from normal to acidosis and from acidosis to alkalosis during dying and in the postreanimation period create highly unfavourable conditions for restoring functions. The experimental data indicate that prompt elimination of acidosis by injecting base — (sodium bicarbonate) or a buffer gives statistically reliable improvement of the outcome of resuscitation.