This proposal has three goals: 1) to define the molecular mechanism whereby the halogenated volatile anesthetics, halothane and isoflurane, decrease beta-adrenergic responsiveness; 2) to define the mechanism whereby alpha2-adrenergic agonists decrease anesthetic requirements for the halogenated volatile anesthetics, halothane and isoflurane; and 3) to determine the clinical efficacy of perioperative treatment with an alpha2-adrenergic agonist in reducing anesthetic and analgetic requirements while maintaining a stable cardiorespiratory state. The tendency of halogenated volatile anesthetic agents to decrease adrenergic responsiveness can be used to clinical advantage when anesthesia is required for the """"""""hyperadrenergic"""""""" patient, or when a sympatholytic effect is desired for a narcotic-based anesthetic technique. Alpha2-adrenergic agonists, which also have sympatholytic properties, have recently been used to supplement anesthesia and analgesia in surgical patients. This proposal will determine the mechanisms for these actions. Our methodology involves three objects of study. First, we will use isolated fat cells to examine the effects of halothane and isoflurane on each step in the biochemical cascade of isoproterenol-stimulated lipolysis, a beta-adrenergic response. Second, we will study rats to define the individual contributions of the pre- and postsynaptic effects of alpha2-adrenergic agonists to the decrease in anesthetic requirements. Third, we will investigate the anesthetic, analgesic, and cardiorespiratory effects of continuous therapy with alpha2-adrenergic agonists in surgical patients. The resulting data will describe how volatile anesthetic agents act as sympatholytic agents and how alpha2-adrenergic agonists modulate the anesthetic response. Also we will establish the clinical utility of therapy with alpha2-adrenergic agonists in surgical patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM030232-04A2
Application #
3277877
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1983-03-01
Project End
1993-02-28
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
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