The molecular effect of general anesthesia on alveolar macrophages

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HUMAN STUDY : We studied patients anesthetized with propofol (n=30) or isoflurane (n=30) during major orthopedic surgery. Alveolar macrophages were harvested by bronchoalveolar lavage immediately, and 2,4, and 6 hours after induction anesthesia and at the end of surgery. The fraction of aggregated and nonviable macrophages was determined. We then measured phagocytosis by ingestion of opsonized and unopsonized particles. Finally, microbicidal activity was determined as the ability of the macrophages to directly kill Listeria monocytogenes.The fraction of alveolar macrophages ingesting opsonized and non-opsonized particles, and the number of particles ingested, decreased significantly over time, with the decrease being slightly but significantly greater during isoflurane anesthesia. Microbicidal function progressively decreased during anesthesia and surgery, with the decrease being almost twice as great during isoflurane than propofol anesthesia. The fraction of aggregated macrophages and recovered neutrophils increased over time in the patients given each anesthetic.ANIMAL STUDY : Rats received a tracheostomy followed by mechanical ventilation. We performed bronchoalveolar lavage to harvest AMs at the following time points : after two-hour mechanical ventilation without inhaled anesthetics, after two-hour mechanical ventilation with 1-MAC isoflurane, and after two-hour mechanical ventilation with 1-MAC halothane. We extracted RNAs and cDNA was synthesized with reverse transcriptase. We used specific 3'- and 5'-primers for four cytokines : IL-1alpha and beta, IL-6, IFN and TNF-alpha and macrophage inflammatory protein-2 (MIP-2). Before the experiment, we established the PCR condition that resulted in exponential amplification. For all cytokines, gene expression of all cytokines was minimal after two-hour mechanical ventilation without anesthetics. We found gene expression of IL-1, IFN,and TNF two hours after mechanical ventilation with isoflurane.