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Original communication| Volume 87, ISSUE 5, P573-580, May 1980

Alteration of lymphocyte function due to anesthesia: In vivo and in vitro suppression of mitogen-induced blastogenesis by sodium pentobarbital

  • Joseph F. Formeister
    Footnotes
    Affiliations
    From the Divisions of Surgery, Immunology and Gastroenterology, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D.C., USA

    From the Howard Hughes Medical Research Institute and Division of Gastroenterology, Washington University Medical Center, St. Louis, Mo, USA

    From the Department of Microbiology, University of Maryland, College Park, Md., USA
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  • Richard P. MacDermott
    Correspondence
    Reprint requests: Richard P. MacDermott, M.D., Division of Gastroenterology, Box 8124, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110.
    Affiliations
    From the Divisions of Surgery, Immunology and Gastroenterology, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D.C., USA

    From the Howard Hughes Medical Research Institute and Division of Gastroenterology, Washington University Medical Center, St. Louis, Mo, USA

    From the Department of Microbiology, University of Maryland, College Park, Md., USA
    Search for articles by this author
  • Dennis Wickline
    Affiliations
    From the Divisions of Surgery, Immunology and Gastroenterology, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D.C., USA

    From the Howard Hughes Medical Research Institute and Division of Gastroenterology, Washington University Medical Center, St. Louis, Mo, USA

    From the Department of Microbiology, University of Maryland, College Park, Md., USA
    Search for articles by this author
  • Diana Locke
    Affiliations
    From the Divisions of Surgery, Immunology and Gastroenterology, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D.C., USA

    From the Howard Hughes Medical Research Institute and Division of Gastroenterology, Washington University Medical Center, St. Louis, Mo, USA

    From the Department of Microbiology, University of Maryland, College Park, Md., USA
    Search for articles by this author
  • Geoffrey S. Nash
    Affiliations
    From the Divisions of Surgery, Immunology and Gastroenterology, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D.C., USA

    From the Howard Hughes Medical Research Institute and Division of Gastroenterology, Washington University Medical Center, St. Louis, Mo, USA

    From the Department of Microbiology, University of Maryland, College Park, Md., USA
    Search for articles by this author
  • David G. Reynolds
    Footnotes
    Affiliations
    From the Divisions of Surgery, Immunology and Gastroenterology, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D.C., USA

    From the Howard Hughes Medical Research Institute and Division of Gastroenterology, Washington University Medical Center, St. Louis, Mo, USA

    From the Department of Microbiology, University of Maryland, College Park, Md., USA
    Search for articles by this author
  • Bob S. Roberson
    Affiliations
    From the Divisions of Surgery, Immunology and Gastroenterology, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D.C., USA

    From the Howard Hughes Medical Research Institute and Division of Gastroenterology, Washington University Medical Center, St. Louis, Mo, USA

    From the Department of Microbiology, University of Maryland, College Park, Md., USA
    Search for articles by this author
  • Author Footnotes
    † The authors deeply regret the death of Dr. Joseph F. Formeister on Feb. 7, 1979. His untimely passing was a personal and scientific loss deeply felt by the authors, Dr. Formeister's surgical colleagues, and all who knew him as a dedicated physician and researcher.
    ∗ Present address: Department of Surgery, University of Iowa, Iowa City, IA 52242.
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      Abstract

      The mechanism of decreased lymphocyte responsiveness after major surgery is unclear. Because sodium pentobarbital, an intermediately long-acting barbiturate, will reproducibly induce anesthesia in experimental animals, we utilized a canine model to investigate its effect on lymphocyte proliferation induced by the mitogenic lectins erythroagglutinating phytohemagglutinin (E-PHA) and leukoagglutinating phytohemagglutinin (L-PHA). Although no effect was observed at 10 minutes or 1 hour after an anesthetic dose of sodium pentobarbital, after 2 and 3 hours of anesthesia, canine lymphocytes were significantly suppressed, as demonstrated by decreased responsiveness to E-PHA and L-PHA mitogen stimulation. After 3-hours the majority of animals had mitogenesis values of less than 50% of the preanesthetic control values. Recovery, as measured by a return to at least 70% of the preanesthetic mitogenesis value, was noted in the majority of animals at 24, 48, and 72 hours. In order to investigate the mechanisms of the in vivo capability of sodium pentobarbital to induce immunosuppression of lymphocyte transformation, in vitro studies were earned out. Sodium pentobarbital was found to significantly inhibit mitogen-induced canine mononuclear cell blastogenesis at anesthetic (1.5 to 3.0 mg%) drug concentrations in vitro. Lymphocytes pretreated with barbiturate and washed prior to plating did not show this inhibiting effect. Our findings suggest that depression of the immune response reported in patients after operation could result from short-acting barbiturates administered during the induction phase of clinical anesthesia. Furthermore, the suppression may involve in vivo metabolism of pentobarbital, hormones or other in vivo factors, since washed lymphocytes from the in vivo but not the in vitro experiments demonstrated suppression. These results indicate that anesthesia may be an important factor in the immunosuppression reported after major surgery.
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