150,000 Americans/yr suffer severe head injuries; 1/3 require anesthesia and surgery. Another 25-30,000 undergo anesthesia/surgery for intracranial tumors or vascular disorders. Such patients often need large amounts of intravenous fluid, either for resuscitation, replacement of intraoperative blood/fluid losses, or as therapy for ischemia. For the last 2+yrs, we have tried to examine the impact of these fluids on the brain, particularly the role of colloid oncotic pressure (COP), but experiments have demonstrated few differences between isotonic fluids and no effects of reducing COP on brain edema, intracranial pressure, EEG, or cerebral blood flow. This directly contradicts a widely held belief in the adverse effects of crystalloid solutions (e.g. lactated Ringer's). However, our work has focused on the period just after brain damage (<3 hrs), and delayed effects are possible (likely?). If continuation of support is awarded, we will try to determine if such delayed differences between crystalloids and colloids (e.g. hetastarch) exist, both when fluids are given acutely after injury (and brains examined 8 hrs later), and when administration is instituted approximately 24 hrs later, as occurs when patients are brought to the OR after a long delay. In addition, our attention has been drawn to a closely related area. The patients noted above also require anesthesia but while data exists the on effects of anesthetics on normal brain, our understanding of their effects on damaged brain is virtually nonexistent. We believe that anesthetics may act differently in the presence of brain injuries and that some anesthetics may alter the pathophysiologic progression of brain injury. We thus intend to ask 2 questions (which are reflected in the minor title change of this proposal): How does brain injury alter the cerebrovascular, metabolic, and electrophysiologic responses to anesthetics (compared with normal brain)? and Can anesthesia change the development of injury-induced changes in brain edema, ICP, etc.? It is hoped that all of these studies will improve our understanding of brain injury and anesthetic action, permit a more rational practice of neurosurgical anesthesia, and improve perioperative care of neurosurgical patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024517-05
Application #
3409177
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1986-06-01
Project End
1993-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Tomiyama, Y; Jansen, K; Brian Jr, J E et al. (1999) Hemodilution, cerebral O2 delivery, and cerebral blood flow: a study using hyperbaric oxygenation. Am J Physiol 276:H1190-6
Perkins, K L (1999) Cl- accumulation does not account for the depolarizing phase of the synaptic GABA response in hippocampal pyramidal cells. J Neurophysiol 82:768-77
Hansen, T D; Warner, D S; Traynelis, V C et al. (1994) Plasma osmolality and brain water content in a rat glioma model. Neurosurgery 34:505-11;discussion 511
Todd, M M; Wu, B; Warner, D S et al. (1994) The dose-related effects of nitric oxide synthase inhibition on cerebral blood flow during isoflurane and pentobarbital anesthesia. Anesthesiology 80:1128-36
Todd, M M; Wu, B; Warner, D S (1994) The hemispheric cerebrovascular response to hemodilution is attenuated by a focal cryogenic brain injury. J Neurotrauma 11:149-60
Todd, M M; Wu, B; Maktabi, M et al. (1994) Cerebral blood flow and oxygen delivery during hypoxemia and hemodilution: role of arterial oxygen content. Am J Physiol 267:H2025-31
Todd, M M; Weeks, J B; Warner, D S (1993) Microwave fixation for the determination of cerebral blood volume in rats. J Cereb Blood Flow Metab 13:328-36
Verhaegen, M J; Todd, M M; Hindman, B J et al. (1993) Cerebral autoregulation during moderate hypothermia in rats. Stroke 24:407-14
Warner, D S; McFarlane, C; Todd, M M et al. (1993) Sevoflurane and halothane reduce focal ischemic brain damage in the rat. Possible influence on thermoregulation. Anesthesiology 79:985-92
Todd, M M; Weeks, J B; Warner, D S (1993) The influence of intravascular volume expansion on cerebral blood flow and blood volume in normal rats. Anesthesiology 78:945-53

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