The long-term objective of the proposed research is to learn more about: 1) the effects of anesthetic agents on cerebral blood flow (CBF) and metabolism (CMR); 2) the relationships of these effects to basic pathomechanisms of focal ischemia; and 3) ways of modifying outcome from such ischemia insults occurring during anesthesia and surgery.
Our specific aims are to test the hypotheses that: 1) the extent of permanent injury resulting from focal ischemia is related to the anesthetic present during the insult; 2) acute anesthetic- induced changes in CBF and CMR can be related to outcome: 3) the volume of brain tissue at risk for infarction is related to the manner in which different anesthetics preserve or alter the matching of CBF and CMR; 4) anesthetic effects on CBF and CMR relationships vary with time; and 5) the duration of anesthetic exposure prior to the ischemic insult will influence the volume of tissue """"""""at risk"""""""" and this may vary with anesthetic agent. The following methodology will be used to test our hypotheses. Physiologically stable rats will be anesthetized with specific doses of isoflurane, halothane, or pentobarbital with duration of anesthetic exposure carefully controlled. Anesthetic effects on regional CBF and CMR will be simultaneously quantitated by 14C- iodoantipyrine and 14C-deoxglucose autoradiography respectively. Volume of ischemic tissue at risk for infarction as a result of middle cerebral artery occlusion will be determined by computer- assisted image analysis. This volume will then be related to anesthetic dose/response effects on CBF/CMR ratios. Outcome will be evaluated by: 1) computed quantitative 3-dimensional reconstruction of infarct volumes; 2) behavioral patterns; and 3) densitometric determination of brain water content. The health relatedness of this proposal derives from the fact that numerous conditions requiring surgery predispose patients to potentially disastrous cerebral ischemic insults while receiving anesthesia (e.g. carotid endarterectomy, cardiopulmonary bypass). Significant advances have been made in understanding basic pathomechanisms of cerebral ischemia and anesthetic effects on cerebral physiology, yet indications for application or avoidance of various anesthetic techniques during potentially ischemic clinical situations remain poorly defined. The proposed studies will contribute to our understanding of these problems.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
First Independent Research Support & Transition (FIRST) Awards (R29)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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University of Iowa
Schools of Medicine
Iowa City
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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; 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
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
Todd, M M; Weeks, J B; Warner, D S (1993) A focal cryogenic brain lesion does not reduce the minimum alveolar concentration for halothane in rats. Anesthesiology 79:139-43
Verhaegen, M J; Todd, M M; Warner, D S (1992) A comparison of cerebral ischemic flow thresholds during halothane/N2O and isoflurane/N2O anesthesia in rats. Anesthesiology 76:743-54
Warner, D S; Gionet, T X; Todd, M M et al. (1992) Insulin-induced normoglycemia improves ischemic outcome in hyperglycemic rats. Stroke 23:1775-80;discussion 1781
Verhaegen, M; Todd, M M; Warner, D S (1992) The influence of different concentrations of volatile anesthetics on the threshold for cortical spreading depression in rats. Brain Res 581:153-5
Ridenour, T R; Warner, D S; Todd, M M et al. (1992) Comparative effects of propofol and halothane on outcome from temporary middle cerebral artery occlusion in the rat. Anesthesiology 76:807-12
Verhaegen, M J; Todd, M M; Warner, D S et al. (1992) The role of electrode size on the incidence of spreading depression and on cortical cerebral blood flow as measured by H2 clearance. J Cereb Blood Flow Metab 12:230-7

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