title: Effects of halothane on surfactant biosynthesis by rat alveolar type II cells in primary culture.
abstract: BACKGROUND
  Pulmonary surfactant, which is synthesized by alveolar type II cells (ATII cells) almost exclusively, plays a major role in maintaining alveolar homeostasis by reducing surface tension at the fluid-gas interface. Phosphatidylcholine (PC), the main surfactant lipid component, is largely responsible for this surface activity. The effects of halothane on the phospholipid metabolism of the pulmonary surfactant by ATII cells are unknown, even though these cells are exposed directly to volatile anesthetics during anesthesia and even though any alteration in surfactant biosynthesis by anesthetics may have deleterious effects on lung function and thereby facilitate postoperative pulmonary complications. In the current study, the effects of halothane exposure on surfactant synthesis by rat ATII cells in primary culture were investigated.
  
  
  METHODS
  ATII cells were isolated from adult rat lungs and used for the experiments after 24 h in primary culture. The ability of ATII cells to synthesize surfactant was assessed by the incorporation of radioactive precursors in PC. Cytotoxicity was measured by the rate 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. Effects of various halothane concentrations (1, 2, 4, and 8%) exposure for 4 h were studied, as were the effects of 2% halothane for various durations 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 also 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 exposure, respectively. The inhibitory effect of halothane was completely reversed 2 h after the end of exposure. PC secretion was unaffected by increasing 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 that halothane decreases the biosynthesis of pulmonary surfactant by ATII cells in primary culture and alters the high energy phosphate metabolism of these cells.
authors.affiliation: Département d'Anesthésie, Universitaire (CHRU) de St. Etienne, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Molliex
authors.forename: B
authors.initials: B
authors.lastname: Crestani
authors.forename: B
authors.initials: B
authors.lastname: Dureuil
authors.forename: J
authors.initials: J
authors.lastname: Bastin
authors.forename: C
authors.initials: C
authors.lastname: Rolland
authors.forename: M
authors.initials: M
authors.lastname: Aubier
authors.forename: J M
authors.initials: JM
authors.lastname: Desmonts
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006221:Halothane / Q000494:pharmacology* / Q000633:toxicity; D007773:Lactates / Q000096:biosynthesis; D008297:Male; D010713:Phosphatidylcholines / Q000096:biosynthesis / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D011663:Pulmonary Surfactants / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007773:Lactates; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D000255:Adenosine Triphosphate; D005947:Glucose; D006221:Halothane