The present results show a close relation between changes in SEF and TCD blood flow velocity during acute hemorrhagic hypotension. SEF and TCD velocity were constant during the decrease of MAP to a level of 55% from baseline. This is consistent with preserved CBF autoregulation [6,8]. Further decreases in MAP produced a shift of the EEG to lower frequencies parallel to decreases in Vmean and Vdiast. At MAP levels of 31 +/- 7 mm Hg, EEG burst suppression occurred. Concurrently, a loss of the diastolic flow velocity pattern was seen. This shows that the diastolic TCD blood flow velocity and neuronal function are closely correlated. Although CBF was not measured during the present study these results suggest that the diastolic flow pattern is an indicator of severe cerebral ischemia as a function of CPP.
Previous studies have shown that arterial hypotension beyond the lower limit of CBF autoregulation produces typical changes in the EEG pattern that are related to progressive cerebral ischemia and concurrent neuronal dysfunction. Stockard et al.  studied the relation between different arterial blood pressure levels during cardiopulmonary bypass and postoperative neurologic status. They found that EEG slowing or isoelectricity and postoperative neurologic deficits were correlated in a time-dependent fashion. This is consistent with an investigation in patients undergoing carotid endarterectomy where 50% decreases in SEF for a period of 10 min were correlated with the development of postoperative neurologic deficits . Based on these investigations, the SEF was used here to measure the effects of progressive systemic hypotension on neuronal function in comparison to cerebral hemodynamics assessed by the TCD technique although the time frame of the present experiment may differ from previous studies.
The induction of ischemic EEG changes may occur at different levels of MAP. Kovach and Sandor  found EEG impairment at MAP levels of 50-60 mm Hg with subsequent isoelectricity at MAP levels of 30-40 mm Hg in unanesthetized cats and dogs. In contrast, Gregory et al.  have shown that brain electrical activity did not change over a MAP range of 120-40 mm Hg when chloralose-anesthetized cats were subjected to graded hypotension. Below this pressure the EEG became slower and isoelectricity occurred within a MAP range of 15-30 mm Hg. This is consistent with the present data showing EEG slowing at MAP of less than 49 +/- 9 mm Hg and EEG burst suppression at MAP of 31 +/- 7 mm Hg. Yashon et al.  have shown that neuronal activity may be preserved in barbiturate-anesthetized dogs despite rapid reduction of MAP as low as 30 mm Hg. The differences in the cerebral ischemic threshold seen in these studies may be a function of rapid versus graded induction of systemic hypotension with recruitment of collateral perfusion with graded hypotension. Cerebral metabolic suppression using barbiturates and reduction of sympathetic tone with the use of ganglionic blockade may additionally increase the neuronal tolerance during hypotensive challenges [12,13].
Several studies have evaluated the changes of the TCD blood flow velocity pattern during various ischemic challenges. Clinical investigations by Padayachee et al.  and Naylor et al.  suggest a linear correlation between carotid stump pressure and decreases in Vmean during internal carotid cross-clamping. This supports results by Jorgensen et al.  who found stump pressure values of <40 mm Hg together with Vmean of less than 30 cm/s as an accurate indicator of cross-clamp CBF values of less than 20 mL centered dot 100 g-1 centered dot min-1. Halsey et al.  compared TCD, EEG, and CBF measurements in patients undergoing carotid endarterectomy. Their results suggest a threshold of <15 cm/s of the MCA mean blood flow velocity to indicate focal cerebral ischemia produced by internal carotid cross-clamping. However, this threshold for blood flow velocity was not always paralleled by either low CBF or ischemic EEG changes, indicating a low specificity and sensitivity. Giller et al.  and Spencer et al.  found a close correlation between decreases in average MCA blood flow velocity (>65%) and changes in CBF, stump pressure as well as clinical symptoms of cerebral ischemia in awake patients undergoing balloon occlusion tests of the internal carotid artery. Although these studies show that monitoring of relative or absolute changes in mean blood flow velocity may be inadequate to reproducibly detect focal or hemispheric ischemia, the present experiments show a close relation between changes in SEF and the diastolic blood flow velocity during incomplete global ischemia.
With progressive hemorrhagic hypotension, the induction of EEG burst suppression was paralleled by decreases of the diastolic MCA blood flow velocity to zero. This is consistent with TCD flow patterns observed in laboratory animals and patients with head injury or after subarachnoid hemorrhage, where decreases in Vdiast and a reduction of the cerebral arteriographic filling occurred parallel to increases in ICP [5,6,21-25]. Loss of the diastolic flow velocity pattern may be due to collapse of downstream vessels as diastolic arterial blood pressure decreases below the critical closing pressure . It is also possible that diastolic circulatory arrest is a function of CPP reduction along the still patent vascular bed . Studies in patients have shown that transient cessation of diastolic TCD flow may occur in the early stages of subarachnoid hemorrhage , cerebral anoxia , or with acute intracranial hematoma . This early diastolic cerebral circulatory arrest is potentially reversible. The interval between loss of diastolic flow and irreversible neuronal injury may last as long as 150 min . This suggests that loss of the diastolic flow pattern represents a level of CBF at which neuronal function is deteriorated while structural neuronal metabolism may be still maintained. However, it is possible that a combination of hypoxemia and hypoperfusion may lead to EEG burst suppression before loss of diastolic blood flow velocity occurs (i.e., TCD blood flow velocity is nonquantitative with respect to defining outcome).
In conclusion, the present results show that SEF and TCD blood flow velocity remain constant during acute hemorrhagic hypotension to a level of 55% from baseline. This indicates maintained cerebral autoregulation with preserved neuronal function. MAP levels sufficient to produce EEG burst suppression were paralleled by loss of the diastolic flow velocity pattern. This shows that the diastolic TCD blood flow velocity and neuronal function are closely correlated.
The authors wish to thank Richard Ripper and George Dominguez for their excellent technical assistance.
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