EFFECTS OF HALOTHANE ON SURFACTANT BIOSYNTHESIS BY RAT ALVEOLAR TYPE-II CELLS IN PRIMARY CULTURE

Background: Pulmonary surfactant, which is synthesized by alveolar typ e II cells (ATII cells) almost exclusively, plays a major role in main taining alveolar homeostasis by reducing surface tension at the fluid- gas interface. Phosphatidylcholine (PC), the main surfactant lipid com ponent, is largely responsible for this surface activity. The effects of halothane on the phospholipid metabolism of the pulmonary surfactan t by ATII cells are unknown, even though these cells are exposed direc tly to volatile anesthetics during anesthesia and even though any alte ration in surfactant biosynthesis by anesthetics may have deleterious effects on lung function and thereby facilitate postoperative pulmonar y complications. In the current study, the effects of halothane exposu re on surfactant synthesis by rat ATII cells in primary culture were i nvestigated. Methods: ATII cells were isolated from adult rat lungs an d used for the experiments after 24 h in primary culture, The ability of ATII cells to synthesize surfactant was assessed by the incorporati on of radioactive precursors in PC. Cytotoxicity was measured by the r ate of lactate dehydrogenase release into the culture medium, and the lactate metabolism was taken as an index of glycolytic metabolism. All metabolic measurements were made after 24 h in primary culture. Effec ts of various halothane concentrations (1, 2, 4, and 8%) exposure for 4 h were studied, as were the effects of 2% halothane for various dura tions of exposure (2, 4, 8, and 12 h). The reversibility of halothane effects on PC synthesis was assessed after a 2% halothane exposure for 4 h. PC secretion and adenosine triphosphate cellular content were al so measured for 4 h exposure at the various halothane concentrations. Results: During a 4-h exposure, PC synthesis was reduced by 10, 24, 29 and 36% for 1, 2, 4, and 8% halothane respectively when compared with control values. At 2% halothane concentration, the observed decreases in PC synthesis were 12, 24, 31 and 34% for 2, 4, 8, and 12 h exposur e, respectively. The inhibitory effect of halothane was completely rev ersed 2 h after the end of exposure. PC secretion was unaffected by in creasing halothane concentrations during a 4-h exposure. Halothane did not produce cell damage except for the longest exposure durations (8 and 12 h) at 2% vapor concentration. Whatever the exposure conditions, lactate production by ATII cells exposed to halothane was greater than production by unexposed cells. Conclusions: These results indicate th at halothane decreases the biosynthesis of pulmonary surfactant by ATI I cells in primary culture and alters the high energy phosphate metabo lism of these cells.