July 1997
Volume 61 |
Number 7
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FAER REPORT
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| FAER Announces
1997 New Investigator Award Recipients |
The Board of Directors of the Foundation for Anesthesia Education
and Research (FAER) is pleased to announce the recipients of the
1997 New Investigator Awards. The ASA Committee on Research reviewed
28 applications and identified many projects worthy of funding.
FAER was able to fund eight of these projects thanks to the generous
contributions of FAER's corporate and society sponsors. The descriptions
of five of the eight projects are outlined below:
Joseph F. Antognini, M.D., FAER/Abbott Laboratories New Investigator,
University of California, Davis School of Medicine, Davis, California:
"The Effect of Differential Isoflurane Delivery to Brain
and Spinal Cord on Inhibitory and Excitatory Output from the Brain"
The mechanisms and sites of anesthetic action are unknown.
Recent studies suggest that anesthetics acts in the spinal cord
to suppress movement in response to noxious stimuli, although
the brain can influence anesthetic requirements. We hypothesize
that isoflurane has differential effects on the inhibitory/excitatory
balance within the brain (midbrain reticular formation) and
spinal cord (dorsal horn, motor neurons). In goats, we will
selectively perfuse and anesthetize the brain, thereby permitting
administration of a different anesthetic concentration to the
brain than to the spinal cord. Concurrently, we will determine
the inhibitory/excitatory balance within the spinal cord and
brain using microelectrodes placed in the dorsal horn, MRF neurons
and by measuring spontaneous and evoked motor activity. Understanding
the relationship between the brain and spinal cord vis-á-vis
anesthetic action might explain certain clinical phenomena (stage
two excitement, emergence delirium), will guide further research,
and eventually will lead to more site-specific anesthetics.
Helene Benveniste, M.D., Ph.D., FAER/The American Society
of Regional Anesthesia New Investigator, Duke University Medical
Center, Durham, North Carolina: "In vivo Magnetic
Resonance Microscopy of Continuous Spinal Anesthesia: Mechanisms
of Local Anesthesia Neurotoxicity"
Persistent neurologic deficits after continuous spinal anesthesia
in patients using hyperbaric 5 percent lidocaine have been reported.
As a consequence, the FDA withdrew manufacturers' marketing
approvals for small-bore catheters for intrathecal use. The
pathophysiological mechanisms underlying the neurologic complications
are not clear but might be related to use of higher than normal
doses of hyperbaric 5 percent lidocaine and spinal microcatheters
directed sacrally. Today patients are increasingly exposed to
local anesthetics when peripheral-or central nervous blockade
is used during surgery or post-operatively for analgesia. To
avoid future complications it is important to determine the
etiology of local anesthetic-induced neurotoxicity and to determine
how to control its occurrence. We will pioneer the use of diffusion-weighted
magnetic resonance microscopy in the study of local anesthesia
neurotoxicity in vivo. It is our long-term goal that data derived
from this research will help guide future clinical use of existing
and new local anesthetics.
Pamela Flood, M.D., FAER/Ohmeda, Inc. New Investigator,
College of Physicians & Surgeons of Columbia University,
New York, New York: "General Anesthetic Activity at Neuronal
Nicotinic Acetylcholine Receptors"
The objective of this project is to investigate the activity
of general anesthetics on neuronal type nicotinic acetylcholine
receptors (nAChRs), a family of ligand gated ion channels important
in the function and regulation of the central and autonomic
nervous systems. The activity of general anesthetics at members
of the nAChR family is the most potent demonstrated. This work
will add to our knowledge of the activity of general anesthetic
mechanism. Through the study of the modulation of chimeric nAChRs
by general anesthetics, we hope to understand the molecular
nature of general anesthetic-nAChR interaction. The combination
of knowledge of the receptor specific activity of general anesthetics
and the molecular nature of anesthetic-receptor interaction
will allow for both the development of more specific anesthetic
agents and more refined application of those currently in use.
Ferenc E. Gyulai, M.D., FAER/Mallinckrodt Medical, Inc. New
Investigator, University of Pittsburgh, Pittsburgh, Pennsylvania:
"Quantitative Tests of the GABAA-Receptor Hypothesis
of Volatile General Anesthetic Action Using In Vivo Human
Brain Imaging"
Abundant in vitro studies suggest that one of the targets
for volatile anesthetics is the gamma-aminobutyric acidergic
(GABA) receptor in the brain. The clinical relevance of these
findings, however, remains unclear. Our laboratory has recently
provided the first in vivo human evidence that the volatile
anesthetic, isoflurane, evokes dose-dependent conformational
changes of the GABAA-receptor using positron emission
tomography (PET). This noninvasive technique measures receptor-specific
radiolabeled ligand binding as a reflection of its affinity
and consequently, receptor macromolecule conformation. Using
PET, the current experiments will test the specificity of isoflurane's
effect in the living human brain by measuring GABAA-receptor
conformational changes in the presence of equipotent doses of
anesthetics of significantly different potency and agents known
to have insignificant effects on this receptor. Furthermore,
the receptor-specificity of isoflurane will also be tested by
measuring its effect on the conformation of the G protein-coupled
5HT2A-receptor known to be insensitive to anesthetics.
The proposed studies represent the validation of a methodology
that could significantly contribute to the development of clinically
safer anesthetic agents.
Keith A. Hunter, M.D., FAER/Arrow International New
Investigator, Howard University Hospital, Washington, D.C.:
"Regulation of Heme Oxygenase in Response to Acute Lung Injury
and Sepsis"
The goal of this research project is to learn more about
the function of a stress-related enzyme called Heme oxygenase.
This enzyme becomes more active when animals or cells are exposed
to excessive heat and abnormal concentrations of oxygen. The
substance that causes animals and cells to become sick during
an infection also increases the activity of heme oxygenase and
we believe that this has a protective effect. One of our goals
is to determine the mechanism involved in this protection. A
second goal is to elucidate whether infection increases the
enzyme activity directly or whether there are intermediary substances
known as cytokines that serve as messengers. The third area
of study will be in the regulation and control of the enzyme.
By understanding this enzyme, we hope to find more ways to decrease
injury to cells and ultimately people.
Because of space restrictions, other recipients of 1997 New Investigator
Awards will be featured in upcoming issues of the "FAER Report."
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