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depolarization, which occurs when a cell cannot maintain its normal ionic gradients. This occurs when the normal adenosine triphosphate (ATP) supply has been depleted to approximately 15% of its baseline value. This value is relatively independent of the nature of the ischemic environment, whether it is normothermic awake, normothermic with a particular anesthetic, or hypothermic. However, the length of the window will vary from roughly 2 to 5 min, depending on the environment. Clinically, we detect depolarization when the EEG becomes isoelectric, although the correlation is not perfect. Different environments can result in similar times to EEG isoelectricity, but substantially different times to depolarization. This discrepancy results from the fact that the brain has two major activities that require energy, that of normal cellular maintenance and that of synaptic transmission. The EEG monitors synaptic activity, but the largest use of energy is for cellular maintenance, and is not readily monitored. Factors that affect the ratio between these two energy expenditures will affect the length of the "window of opportunity." Fortunately, the EEG changes dramatically long before isoelectricity occurs, and is still the earliest warning monitor of ischemia. Near infrared spectroscopy is another monitor that shows significant change during this time and if allowed by the surgical procedure, monitoring the brain while awake is another technique that detects ischemia during this time.
Once this rather brief window of opportunity of approximately 5 min has passed, other more permanent and devastating changes occur. After isoelectricity occurs on the EEG, DC potential shifts can occur, and tissue surrounding the central, most ischemic area demonstrates transient or sustained depolarizations. These processes consume energy and spread through peri-ischemic regions, increasing the area of ischemic damage. Other changes during this time period include declining intracellular pH, release of excitatory neurotransmitters, activation of calcium channels, severe imbalance between metabolism/blood flow, and induction of genes expressing mediators of this process. The largest release of excitatory neurotransmitters occurs late in the ischemic process and is associated with sustained depolaritations.
MRI signals then change, and can detect ischemic change at approximately 15 min. Although these changes occur, they do not necessarily result in permanent neurological damage, and during general anesthesia, the time period before permanent damage occurs varies from 14 to 31 min. The actual times will vary greatly, depending on the nature of the ischemic insult, collateral flow, brain temperature, and other environmental factors.
If ischemia is transient, much damage can occur during reperfusion. Metabolism is severely disturbed in ischemic areas, and (Continued on page 104)
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