The antimicrobial and proinflammatory functions of alveolar macrophages are altered during anesthesia and surgery. Kotani et al. evaluated how previous long-term exposure to cigarette smoke might further affect these functions during halothane and isoflurane anesthesia in rats. Sixty rats were exposed to filter-tipped cigarettes for 30 min/day during a 60-day period using a Hamburg II smoking machine. Sixty additional rats were sham exposed and served as controls during the experiments.
Thirty control and 30 smoke-exposed rats were mechanically ventilated with 1.5 MAC halothane and isoflurane. Ten smoke-exposed and control animals were assigned to one of three different anesthetic durations. Immediately after induction of anesthesia, 10 smoke-exposed and control rats were killed for whole pulmonary lavage. Another 10 others from each group were killed at 2 and 6 h after onset of anesthesia. The lavage fluid was evaluated for total cell count, viability and cell differentiation, and aggregation. Alveolar macrophages were separated from bronchoalveolar lavage fluid by centrifugation, then resuspended in a saline–dextrose solution to determine phagocytosis. Antimicrobial activity of the macrophages was determined by the number of Listeria monocytogenes remaining after a 48-h culturing period. The rate at which the macrophages killed Listeria was determined by comparing bacteria surviving in control (cell-free) tubes with those combined with separated macrophages.
Overall, the concentration and total number of alveolar cells in the lavage fluid were five times greater in the smoke-exposed rats than in the control rats during halothane anesthesia. In rats exposed to smoke and in controls, macrophage aggregation and neutrophil influx increased over the 6-h course of halothane anesthesia, but the aggregation in smoke-exposed rats was twice that of non–smoke-exposed rats. Gene expression and production of proinflammatory cytokines (except for IL-6) increased 2- to 20-fold during anesthesia. The increases in IL-1β, IFN-γ and TNF-α in the control rats were 1.5–8 times greater than those in the smoke-exposed rats.
Extrapolation of the results to humans must be done cautiously, and surgical stress cannot be discounted as a contributor to the augmentation of leukocyte adhesion molecules and activation of neutrophil function. However, even 6 weeks of exposure to cigarette smoke impairs antimicrobial and proinflammatory functions of alveolar macrophages.