The proposed research will examine the action of volatile inhalational anesthetics on the biochemistry of measles virus in vitro and on the pathogenesis of virus infections in patients undergoing surgery and anesthesia. Measles virus will be grown in tissue culture and exposed to various volatile inhalational anesthetics. The mechanism by which halothane, enflurane, or isoflurane affect viral macromolecular synthesis and maturation, especially protein synthesis and processing, will be investigated and compared to cellular protein synthesis and processing in uninfected cultures exposed and not exposed to the volatile anesthetics. We will determine whether anesthetic induced inhibition of protein synthesis occurs at the transcriptional and/or translational level. Anesthetic induced perturbations in phosphorylation and glycosylation of virus proteins will be examined. Anesthetic induced alterations in the levels of cellular mediators such as those which control phosphorylation and glycosylation will be assessed and correlated to observed changes in protein processing. It is believed these studies will help to elucidate the role that anesthetics play in inducing alterations in protein synthesis and processing by altering intracellular messenger levels and/or transduction during virus replication. The clinical studies to date in a pediatric population have suggested an important clinical and economical direction in the practice of anesthesia. The studies described in this proposal will continue and extend these experiments in an adult population who have an upper respiratory tract infection and are undergoing anesthesia for gynecological surgery. By correlating these in vivo results with our in vitro results we hope to establish a firm molecular basis for our clinical findings.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028911-10
Application #
3276267
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1981-04-01
Project End
1993-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
10
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
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