title: Attenuation of acute lung injury with propofol in endotoxemia.
abstract: Endotoxin causes acute lung injury (ALI) through many mediators of inflammatory and immune responses. Propofol is an antiinflammatory and immunosuppressive drug. We conducted this study to evaluate whether propofol attenuates ALI associated with endotoxemia. Thirty-two anesthetized rabbits were randomly divided into four groups (n = 8 each). ALI was induced by IV endotoxin 5 mg/kg over 30 min in 3 groups. In 2 of the ALI groups, IV administration of propofol (2 or 5 mg/kg as a bolus followed by continuous infusion at 4 or 15 mg x kg(-1) x h(-1)) was started 15 min before endotoxin. The other ALI group received soybean-oil emulsion. The nonlung injury control group received infusion of both vehicles. The lungs were mechanically ventilated with 40% oxygen for 6 h after endotoxin. Hemodynamics did not differ among groups. The large dose of propofol attenuated lung leukosequestration, pulmonary edema (as assessed by lung wet/dry weight ratio), and pulmonary hyperpermeability (as assessed by albumin levels in bronchoalveolar lavage fluid) and resulted in better oxygenation, lung mechanics, and histological change. The small dose of propofol failed to do so. Our findings suggest that a large dose of propofol successfully mitigates physiological, biochemical, and histological deterioration in ALI in endotoxemia.
authors.affiliation: Department of Anesthesia & Perioperative Medicine, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Takao
authors.forename: Katsuya
authors.initials: K
authors.lastname: Mikawa
authors.forename: Kahoru
authors.initials: K
authors.lastname: Nishina
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Obara
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019446:Endotoxemia / Q000150:complications* / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics; D030421:Peroxynitrous Acid / Q000378:metabolism; D015742:Propofol / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D012333:RNA, Messenger; D030421:Peroxynitrous Acid; D019001:Nitric Oxide Synthase; D015742:Propofol
references.citation: Ghosh S, Latimer RD, Gray BM, et al. Endotoxin-induced organ injury. Crit Care Med 1993;21:S19–24.
references.citation: Brigham KL, Meyrick B. Endotoxin and lung injury. Am Rev Respir Dis 1986;133:913–27.
references.citation: Schlag G, Redl H. Mediators of injury and inflammation. World J Surg 1996;20:406–10.
references.citation: Aldridge AJ. Role of the neutrophil in septic shock and the adult respiratory distress syndrome. Eur J Surg 2002;168:204–14.
references.citation: Abraham E. Neutrophils and acute lung injury. Crit Care Med 2003;31:S195–9.
references.citation: Spragg RG. Platelets and acute lung injury. In: Artigas A, Lemaire F, Suter PM, Zapol WM, eds. Adult respiratory distress syndrome. New York: Churchill Livingstone, 1992:89–94.
references.citation: Runzer TD, Ansley DM, Godin DV, Chambers GK. Tissue antioxidant capacity during anesthesia: propofol enhances in vivo red cell and tissue antioxidant capacity in a rat model. Anesth Analg 2002;94:89–93.
references.citation: Mikawa K, Akamatsu H, Nishina K, et al. Propofol inhibits human neutrophil functions. Anesth Analg 1998;87:695–700.
references.citation: Galley HF, Dubbels AM, Webster NR. The effect of midazolam and propofol on interleukin-8 from human polymorphonuclear leukocytes. Anesth Analg 1998;86:1289–93.
references.citation: De La Cruz JP, Paez MV, Carmona JA, De La Cuesta FS. Antiplatelet effect of the anaesthetic drug propofol: influence of red blood cells and leucocytes. Br J Pharmacol 1999;128:1538–44.
references.citation: Aoki H, Mizobe T, Nozuchi S, Hiramatsu N. In vivo and in vitro studies of the inhibitory effect of propofol on human platelet aggregation. Anesthesiology 1998;88:362–70.
references.citation: Taniguchi T, Yamamoto K, Ohmoto N, et al. Effects of propofol on hemodynamic and inflammatory responses to endotoxemia in rats. Crit Care Med 2000;28:1101–6.
references.citation: Plummer GF. Improved method for the determination of propofol in blood by high-performance liquid chromatography with fluorescence detection. J Chromatogr 1987;421:171–6.
references.citation: LeSouef PN, Engl SJ, Bryan AC. Total resistance of the respiratory system in preterm infants with and without an endotracheal tube. J Pediatr 1984;104:108–11.
references.citation: Matsukawa A, Yoshimura T, Miyamoto K, et al. Analysis of the inflammatory cytokine network among TNF, IL-1 beta, IL-1 receptor antagonist, and IL-8 in LPS-induced rabbit arthritis. Lab Invest 1997;76:629–38.
references.citation: O’Grady NP, Preas HL, Pugin J, et al. Local inflammatory responses following bronchial endotoxin instillation in humans. Am J Respir Crit Care Med 2001;163:1591–8.
references.citation: Esmon CT. Why do animal models (sometimes) fail to mimic human sepsis? Crit Care Med 2004;32:S219–22.
references.citation: Flecknell PA. Anaesthesia of animals for biomedical research. Br J Anaesth 1993;71:885–94.
references.citation: Gao J, Zeng BX, Zhou LJ, Yuan SY. Protective effects of early treatment with propofol on endotoxin-induced acute lung injury in rats. Br J Anaesth 2004;92:277–9.
references.citation: Samuelsson B, Dahlen SE, Lindgren JA, et al. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 1987;237:1171–6.
references.citation: Rich GF, Roos CM, Anderson SM, et al. Direct effects of intravenous anesthetics on pulmonary vascular resistance in the isolated rat lung. Anesth Analg 1994;78:961–6.
references.citation: Kam PCA, Govender G. Nitric oxide: basic science and clinical applications. Anaesthesia 1994;49:515–21.
references.citation: Martich GD, Boujoukos AJ, Suffredini AF. Response of man to endotoxin. Immunobiology 1993;187:403–16.
references.citation: Nishina K, Mikawa K, Takao Y, et al. ONO-5046, an elastase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits. Anesth Analg 1997;84:1097–103.
references.citation: Mikawa K, Nishina K, Tamada M, et al. Aminoguanidine attenuates endotoxin-induced acute lung injury in rabbits. Crit Care Med 1998;26:905–11.