Abstract
In order to study the problem of how fast and to what degree severe hypoxic brain tissue changes are reversed after reoxygenation, we challenged the viability of the brain by exposing experimental animals to anoxia of such a duration that cardiopulmonary resuscitation was just possible. The brain tissue concentrations of glucose, lactate, pyruvate and of ATP, ADP, AMP and phosphocreatine were determined. Two series of experiments were carried out. In the first, groups of rats deprived of oxygen for 1, 2, 4 and 6 min were studied in order to show brain tissue changes in the period of impending death as well as the changes coinciding with the onset of clinical death (blood pressure zero). In addition, one group maintained at a rectal temperature of 37 +/- 0.5 degrees C and ventilated for 60 min with an oxygen free gas mixture was included aimed at representing a state of irreversibility. In the second series, restitution after 6 min of no oxygen supply was studied 10 min, 1/2 h, 1 h, and 2 h after cardiopulmonary resuscitation. Attempts were also made to correlate biochemical changes to EEG status and to clinical recovery. The restitution study showed that oxidative phosphorylation of the brain tissue was rapidly resumed with normalization of the adenylate energy charge in all animals in which the pump function of the heart could be restored by our artificial means. However, there was a strikingly poor correlation between recovery of mitochondrial function and restitution of EEG or clinical recovery. Thus, it seems likely that a delayed functional restitution is not due to energy failure but to other biochemical changes or to biophysical alterations not revealed by the present type of study.

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