Progressive hypoxia until brain electrical silence: a useful model for studying protective interventions

Anesthetized spontaneously breathing rats, fitted with epicortical electrodes and catheters for sampling arterial, venous, and cerebral venous blood, were exposed to standardized progressive hypoxia. Three minutes of hypoxia sequentially caused hyperpnea, hypopnea, apnea, and cessation of electrocorticogram "spiking," of synchronization, and of background in electroencephalogram (EEG). Blood data and cerebral blood flow and metabolism were measured throughout and at "insults," i.e., at apnea and cessation events, to clarify their interdependence. Arterial and brain venous PO2 fell linearly with inspired oxygen (final value of 2% at 280 s). Hyperpnea induced arterial alkalosis; subsequent hypopnea led to near-normal PCO2 and pH when EEG ceased. Hypercapnia was more pronounced in cerebral than in systemic venous blood; time courses of pH changes were similar. Sagittal sinus blood pressure and outflow were linearly related and resembled the time course of local cerebral blood flow. Blood flow increased by 25% at apnea and only 60% at EEG silence. Cerebral metabolic rate of O2 rose during the hyperpnea phase and fell exponentially thereafter. Cerebral glucose uptake and lactate release increased within the first 3 min but fell abruptly when cortico-electric spiking ceased. Time courses of cerebral O2 consumption and spike rate were linearly related; both showed inverse linear relations to cerebral perfusion. The hypoxic insults were well defined by blood data; critical PO2 values were lower than previously assumed. This model is proving to be a useful, controlled method by which mechanisms of cerebral hypoxia tolerance may be studied in vivo.