title: Halothane potentiates the alcohol-adduct induced TNF-alpha release in heart endothelial cells.
abstract: BACKGROUND: The possibility exists for major complications to occur when individuals are intoxicated with alcohol prior to anesthetization. Halothane is an anesthetic that can be metabolized by the liver into a highly reactive product, trifluoroacetyl chloride, which reacts with endogenous proteins to form a trifluoroacetyl-adduct (TFA-adduct). The MAA-adduct which is formed by acetaldehyde (AA) and malondialdehyde reacting with endogenous proteins, has been found in both patients and animals chronically consuming alcohol. These TFA and MAA-adducts have been shown to cause the release of inflammatory products by various cell types. If both adducts share a similar mechanism of cell activation, receiving halothane anesthesia while intoxicated with alcohol could exacerbate the inflammatory response and lead to cardiovascular injury. METHODS: We have recently demonstrated that the MAA-adduct induces tumor necrosis factor-alpha (TNF-alpha) release by heart endothelial cells (HECs). In this study, pair and alcohol-fed rats were randomized to receive halothane pretreatments intra peritoneal. Following the pretreatments, the intact heart was removed, HECs were isolated and stimulated with unmodified bovine serum albumin (Alb), MAA-modified Alb (MAA-Alb), Hexyl-MAA, or lipopolysaccharide (LPS), and supernatant concentrations of TNF-alpha were measured by ELISA. RESULTS: Halothane pre-treated rat HECs released significantly greater TNF-alpha concentration following MAA-adduct and LPS stimulation than the non-halothane pre-treated in both pair and alcohol-fed rats, but was significantly greater in the alcohol-fed rats. CONCLUSION: These results demonstrate that halothane and MAA-adduct pre-treatment increases the inflammatory response (TNF-alpha release). Also, these results suggest that halothane exposure may increase the risk of alcohol-induced heart injury, since halothane pre-treatment potentiates the HEC TNF-alpha release measured following both MAA-Alb and LPS stimulation.
authors.affiliation: University of Nebraska Medical Center, Department of Internal Medicine, 988090 Nebraska Medical Center, Omaha, NE, 68198-3025, USA. gthiele@unmc.edu.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Thiele
authors.forename: Gary E
authors.initials: GE
authors.lastname: Hill
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Pavlik
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Freeman
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Tuma
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Duryee
authors.forename: Lynell W
authors.initials: LW
authors.lastname: Klassen