Halothane potentiates the alcohol-adduct induced TNF-alpha release in heart endothelial cells

Geoffrey M Thiele,Gary E Hill,Dean J Tuma,Thomas L Freeman,Lynell W Klassen,Jacqueline A Pavlik,Michael J Duryee

doi:10.1186/1471-2253-5-3

Abstract

BackgroundThe 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.MethodsWe have recently demonstrated that the MAA-adduct induces tumor necrosis factor-α (TNF-α) 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-α were measured by ELISA.ResultsHalothane pre-treated rat HECs released significantly greater TNF-α 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.ConclusionThese results demonstrate that halothane and MAA-adduct pre-treatment increases the inflammatory response (TNF-α 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-α release measured following both MAA-Alb and LPS stimulation.

Highlights

The possibility exists for major complications to occur when individuals are intoxicated with alcohol prior to anesthetization
Percentage necrosis of the heart endothelial cells (HECs) was determined by the following formula: % Necrosis = (E-S)/(M-S) × 100 [19], where E is the optical density (OD) of the experimentally induced release of LDH activity from the HECs incubated in the presence of the various concentrations of MAA-Alb, S is the spontaneous release of LDH activity (OD) from HECs incubated with media only, and M is the maximal release of LDH activity (OD) determined by total HEC necrosis induced by exposure to 10% Triton X100 (Fisher Scientific, Fair Lawn, NJ) [19]
Effects of increasing concentrations of MAA-Alb on in vitro HEC cell death In order to determine what concentrations of MAA-Alb would result in cell death of HECs, cells were isolated from chow-fed rats and stimulated with increasing doses of the antigen

Summary

Introduction

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. Trifluoroacetyl chloride (TFA) will react with amine groups to form a distinctive protein termed the TFA-adduct [8]

Methods

Results

Discussion

Conclusion