Electrocortical concomitants of neuroprotection and ischemic damage following cerebral circulatory arrest.

摘要

The aim of this dissertation was to analyze the relationships between cortical DC potential depolarization, neurophysiological reversibility and histologic damage following transient, complete cerebral ischemia, employing membrane stabilizing agents to alter the depolarization. Angiographic characterization of a subclavian collateral network, previously undescribed in the rabbit, permitted development of a method for rapid and reversible cessation of blood flow to the brain. Cerebrocirculatory arrest was produced by basilar artery and collateral ligation followed by snare occlusion of the brachiocephalic trunk. The experimental results indicate that the amplitude and integral of the ischemic depolarization shift (IDS) in DC potential but not the latency were predictive for the rate of recovery of electrocortical activity and neuropathological outcome from complete ischemia. This conclusion was drawn from the following observations. Lidocaine (0.2 mg/kg/min i.v. infusion) delayed the IDS, but only attenuated its amplitude during 3-min and not 5-min ischemia compared to control rabbits. The isoelectric EEG duration and recovery of auditory evoked potentials (AEP) were also enhanced by lidocaine during 3-min but not 5-min ischemia, nor was histologic damage diminished following the latter duration after 24 hrs reperfusion. 3-min ischemia was below the threshold for producing detectable neuronal damage. Phenytoin (25 mg/kg) both delayed and diminished the IDS during 5-min ischemia. This was associated with significantly faster recovery of both spontaneous and evoked electrocortical activity, and markedly diminished neuronal vacuolation, status spongiosus and perivascular glial swelling. Regression analysis revealed significant correlations between electro-physiological parameters and grades of cortical injury. Minimal cortical damage, irrespective of treatment, occurred in animals exhibiting an IDS amplitude {dollar}<{dollar}11 mV, IDS integral {dollar}<{dollar}80 mV-min, isoelectric EEG duration {dollar}<{dollar}18 min, or AEP recovery {dollar}>{dollar}35% of baseline during the first 90 min of reperfusion. The results suggest that cortical damage incurred in this preparation could be accounted for primarily by mechanisms linked to ischemic depolarization. Moreover, the brink of cortical ischemic irreversibility appears to result from a critical level of ionic derangement which can be pharmacologically altered with phenytoin but not lidocaine in the dosages employed.