We propose to continue animal studies concerned with the effects of cerebral ischemia on cerebral blood flow (CBF), cerebral metabolism (CMR0-2), and neurologic outcome with the goal of identifying interventions (pharmacologic and otherwise) which might favorably alter the effects of ischemia. Three types of ischemia will be examined: complete ischemia (either by aortic ligation or a neck tourniquet); incomplete global ischemia (acute hemorrhagic ischemia); and incomplete focal ischemia (middle cerebral artery (MCA) occlusion). Following complete global ischemia in dogs we will determine the effectiveness of nimodipine in improving CBF when given at varying time intervals (up to 1 hour) following reperfusion. In this same model the effects of lidoflazine on CBF and neurologic outcome will be examined. Again in this model the effects of superoxide dismutase and catalase will be examined to determine if free radicals contribute to brain injury. The effect of nimodipine on incomplete focal ischemia will be examined in rabbits as determined by effects on brain metabolites, neurologic function, and brain infarction. In this same model the effects of isoflurane will be examined using similar indices for identifying any beneficial (or deleterious) effects. In the dog model of complete ischemia we will evaluate the effects of varying the volume of stagnant blood in the brain during the period of ischemia on post ischemic CBF and outcome. In the primate model of complete ischemia we will determine the impact of clinically relevant infusions of glucose on neurologic and histopathologic outcome. We will examine the dose response effects of 3 new drugs on CBF and CMR0-2 in the dog: sufentanil, triazolam and R0 15-1788 ( a benzodiazepine antagonist). In the dog we will determine the effects of succinylcholine on CBF, CMR0-2, ICP and EEG in an attempt to clarify the current confusion regarding the potential hazards of this drug. In cats we will determine whether atracurium alters seizure threshold to lidocaine. The effect of nitroprusside on cerebral vascular resistance with and without hypotension will be determined in dogs to separate autoregulatory effects from direct effects. Also in dogs the effect of halothane on autoregulation in response to changing cardiac output will be examined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS007507-20
Application #
3393586
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1978-09-01
Project End
1989-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
20
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Perkins, W J; Milde, L N; Milde, J H et al. (1991) Pretreatment with U74006F improves neurologic outcome following complete cerebral ischemia in dogs. Stroke 22:902-9
Milde, L N; Milde, J H; Gallagher, W J (1990) Effects of sufentanil on cerebral circulation and metabolism in dogs. Anesth Analg 70:138-46
Weglinski, M R; Lanier, W L (1990) The effects of transient hyperglycemia on brain glucose in rats anesthetized with halothane. Anesthesiology 73:291-6
Lanier, W L; Iaizzo, P A; Milde, J H (1990) The effects of intravenous succinylcholine on cerebral function and muscle afferent activity following complete ischemia in halothane-anesthetized dogs. Anesthesiology 73:485-90
Lanier, W L; Milde, J H; Sharbrough, F W (1990) Effects of suxamethonium on the cerebrum following disruption of the blood-brain barrier in dogs. Br J Anaesth 65:708-12
Michenfelder, J D; Milde, J H (1990) Postischemic canine cerebral blood flow appears to be determined by cerebral metabolic needs. J Cereb Blood Flow Metab 10:71-6
Lanier, W L; Perkins, W J; Karlsson, B R et al. (1990) The effects of dizocilpine maleate (MK-801), an antagonist of the N-methyl-D-aspartate receptor, on neurologic recovery and histopathology following complete cerebral ischemia in primates. J Cereb Blood Flow Metab 10:252-61
Black, S; Cucchiara, R F; Nishimura, R A et al. (1989) Parameters affecting occurrence of paradoxical air embolism. Anesthesiology 71:235-41
Mitrakou, A; Milde, J; Michenfelder, J et al. (1989) Rates of lactate appearance and disappearance and brain lactate balance after oral glucose in the dog. Horm Metab Res 21:236-9
Perkins, W J; Lanier, W L; Karlsson, B R et al. (1989) The effect of the excitatory amino acid receptor antagonist dizocilipine maleate (MK-801) on hemispheric cerebral blood flow and metabolism in dogs: modification by prior complete cerebral ischemia. Brain Res 498:34-44

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