The principal investigator of this mentored clinical science award is an anesthesiologist who is seeking advanced training in the physiology and pharmacology of general anesthetic action in native neurons. The long-term objectives of this proposal are two-fold. The first objective is to provide the principal investigator with the training that will allow her to become an independent medical scientist. The second objective is to understand the mechanism by which two general anesthetics cause clinically relevant changes in the sympathetic nervous system. The first objective will be obtained through mentored research and non-research activity including graduate classes in physiology and pharmacology. Training will be enhanced with weekly journal club, data review sessions departmental lecture series and interaction with colleagues. The second objective will be pursued with studies of general anesthetic activity at multiple levels of the sympathetic nervous system. General anesthetic modulation of the sympathetic nervous system allows the patient to undergo surgery without hemodynamic changes that would otherwise be detrimental. Modulation of postsynaptic sympathetic nAChRs will be studied using patch clamp recording of dispersed sympathetic ganglia neurons. General anesthetic activity at presynaptic nAChRs will be studied by monitoring the frequency of spontaneous synaptic transmission between dispersed sympathetic ganglia neurons and visceral motor neuron explants. The effects of anesthetics on excitatory input from the hypothalamus will be studied using patch clamp recording from dispersed hypothalamic neurons. The resulting information will provide understanding of the molecular mechanism underlying one of the anesthetic effects that limit anesthetic safety.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08GM000695-02
Application #
6384938
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Cole, Alison E
Project Start
2000-05-01
Project End
2004-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
2
Fiscal Year
2001
Total Cost
$126,294
Indirect Cost
Name
Columbia University (N.Y.)
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Scott, Jason A; Wood, Margaret; Flood, Pamela (2006) The pronociceptive effect of ondansetron in the setting of P-glycoprotein inhibition. Anesth Analg 103:742-6
Rowley, Thomas J; Daniel, Danette; Flood, Pamela (2005) The role of adrenergic and cholinergic transmission in volatile anesthetic-induced pain enhancement. Anesth Analg 100:991-5
Ho, Kenny K; Flood, Pamela (2004) Single amino acid residue in the extracellular portion of transmembrane segment 2 in the nicotinic alpha7 acetylcholine receptor modulates sensitivity to ketamine. Anesthesiology 100:657-62
Flood, Pamela; Daniel, Danette (2004) Intranasal nicotine for postoperative pain treatment. Anesthesiology 101:1417-21
Rada, Erin M; Tharakan, Elizabeth C; Flood, Pamela (2003) Volatile anesthetics reduce agonist affinity at nicotinic acetylcholine receptors in the brain. Anesth Analg 96:108-11, table of contents
Flood, Pamela; Daniel, Danette (2003) Pronociceptive actions of isoflurane: a protective role for estrogen. Anesthesiology 99:476-9
Flood, Pamela; Sonner, James M; Gong, Diane et al. (2002) Isoflurane hyperalgesia is modulated by nicotinic inhibition. Anesthesiology 97:192-8
Flood, Pamela; Coates, Kristen M (2002) Droperidol inhibits GABA(A) and neuronal nicotinic receptor activation. Anesthesiology 96:987-93
Flood, Pamela; Sonner, James M; Gong, Diane et al. (2002) Heteromeric nicotinic inhibition by isoflurane does not mediate MAC or loss of righting reflex. Anesthesiology 97:902-5
Naguib, Mohamed; Flood, Pamela; McArdle, Joseph J et al. (2002) Advances in neurobiology of the neuromuscular junction: implications for the anesthesiologist. Anesthesiology 96:202-31

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