The proposed research will examine the actions of inhalational anesthetics on the biology and biochemistry on viruses both in vivo and in vitro. Measles virus, herpes simplex virus, and poliovirus will be grown in tissue culture and exposed to various inhalational anesthetics. The mechanism by which the anesthetics affect virus replication will be investigated. This will be done by analyzing virus nucleic acid and protein synthesis as well as virus assembly during exposure of the infected cultures to anesthetics. Since clinical anesthesia is reversed by hyperbaric pressure in vivo, any proposed theory of anesthesia at the molecular level must take into account this observation. We have identified a system using measles virus membrane proteins which are inhibited by inhalational anesthetic exposure. This inhibition is reversed under hyperbaric conditions, therefore, these studies will help gain knowledge into the molecular mechanism of action of anesthetic agents. The results obtained in vitro will be correlated with the in vivo study and involve the examination of patients who have upper respiratory tract infections and are undergoing anesthesia and surgery for myringotomy and tympanostomy tube placement.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028911-06
Application #
3276264
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1981-04-01
Project End
1988-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Public Health
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Markovic, S N; Knight, P R; Murasko, D M (1993) Inhibition of interferon stimulation of natural killer cell activity in mice anesthetized with halothane or isoflurane. Anesthesiology 78:700-6
Bedows, E; Davidson, B A; Williams, B A et al. (1989) Characterization of a halothane-resistant strain of measles virus. Antimicrob Agents Chemother 33:400-3
Tait, A R; Du Boulay, P M; Knight, P R (1988) Alterations in the course of and histopathologic response to influenza virus infections produced by enflurane, halothane, and diethyl ether anesthesia in ferrets. Anesth Analg 67:671-6
Tait, A R; Knight, P R (1987) The effects of general anesthesia on upper respiratory tract infections in children. Anesthesiology 67:930-5
Tait, A R; Knight, P R (1987) Intraoperative respiratory complications in patients with upper respiratory tract infections. Can J Anaesth 34:300-3
Bedows, E; Holland, T C; Knight, P R (1986) Inhibition of herpes simplex virus type 1 replication by halothane. Antimicrob Agents Chemother 29:941-4
Cohen, P J; Bedows, E; Brabec, M J et al. (1985) Hyperbaric pressure of 51 atmospheres is without effect on the depression of oxygen uptake in kidney tissue culture produced by halothane. Life Sci 37:1221-4