A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation

Gary E Hill; Irina Gasanova; Geoffrey M Thiele

doi:doi:10.11648/j.ja.20140201.11

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A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation

Gary E Hill, Irina Gasanova, Geoffrey M Thiele

Received: 28 November 2013 Accepted: Published: 20 December 2013

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Abstract

Background: Inhaled anesthetics, including halothane, iso- and sevoflurane induce proinflammatory cytokine release. Halothane is an inhaled anesthetic agent that is metabolized by the liver into a highly reactive product, trifluoroacetyl chloride, which can react endogenously to form a trifluoroacetyl-adduct (TFA-adduct). The MAA-adduct is formed by acetaldehyde and malondialdehyde reacting with endogenous proteins and is found in both patients and animals post-consumption of alcohol. These TFA and MAA-adducts have been shown to cause the release of proinflammatory cytokines by endogenous inflammatory cells. If both adducts share a similar mechanism of cell activation, receiving general anesthesia following alcohol ingestion could exacerbate the inflammatory response caused by the inhaled general anesthetic halothane and lead to solid organ (including liver and brain) injury. Methods: Control diet and alcohol-fed rats were randomized to receive halothane pretreatments by intraperitoneal injection mixed in sesame oil. Following the intraperitoneal injections, 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 determined. Results: Halothane pre-treated rat HECs demonstrated 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 groups. Conclusion: These results demonstrate that halothane and MAA-adduct pre-treatment will increase the inflammatory response (TNF-α release) in rat HECs following LPS and MAA stimulation in vitro. Also, these results suggest that halothane exposure may increase the risk of alcohol-induced solid organ injury secondary to TNF-induced inflammation. Other investigators have reported similar proinflammatory cytokine release with other (isoflurane and sevoflurane) inhaled anesthetic exposure, suggesting inhaled anesthetics should be used with caution in alcohol consuming humans.

DOI	10.11648/j.ja.20140201.11
Published in	Journal of Anesthesiology (Volume 2, Issue 1, January 2014)
Page(s)	1-7
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Inflammation, Tumor Necrosis Factor, Inhaled Anesthetics, Halothane, Solid Organ Injury, Alcohol

References

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Gary E Hill, Irina Gasanova, Geoffrey M Thiele. (2013). A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation. International Journal of Anesthesia and Clinical Medicine, 2(1), 1-7. https://doi.org/10.11648/j.ja.20140201.11

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Gary E Hill; Irina Gasanova; Geoffrey M Thiele. A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation. Int. J. Anesth. Clin. Med. 2013, 2(1), 1-7. doi: 10.11648/j.ja.20140201.11

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AMA Style

Gary E Hill, Irina Gasanova, Geoffrey M Thiele. A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation. Int J Anesth Clin Med. 2013;2(1):1-7. doi: 10.11648/j.ja.20140201.11

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@article{10.11648/j.ja.20140201.11,
  author = {Gary E Hill and Irina Gasanova and Geoffrey M Thiele},
  title = {A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation},
  journal = {International Journal of Anesthesia and Clinical Medicine},
  volume = {2},
  number = {1},
  pages = {1-7},
  doi = {10.11648/j.ja.20140201.11},
  url = {https://doi.org/10.11648/j.ja.20140201.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ja.20140201.11},
  abstract = {Background: Inhaled anesthetics, including halothane, iso- and sevoflurane induce proinflammatory cytokine release. Halothane is an inhaled anesthetic agent that is metabolized by the liver into a highly reactive product, trifluoroacetyl chloride, which can react endogenously to form a trifluoroacetyl-adduct (TFA-adduct). The MAA-adduct is formed by acetaldehyde and malondialdehyde reacting with endogenous proteins and is  found in both patients and animals post-consumption of alcohol. These TFA and MAA-adducts have been shown to cause the release of proinflammatory cytokines by endogenous inflammatory cells. If both adducts share a similar mechanism of cell activation, receiving general anesthesia following alcohol ingestion could exacerbate the inflammatory response caused by the inhaled general anesthetic halothane and lead to solid organ (including liver and brain) injury. Methods: Control diet and alcohol-fed rats were randomized to receive halothane pretreatments by intraperitoneal injection mixed in sesame oil. Following the intraperitoneal injections, 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 determined. Results: Halothane pre-treated rat HECs demonstrated 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 groups. Conclusion: These results demonstrate that halothane and MAA-adduct pre-treatment will increase the inflammatory response (TNF-α release) in rat HECs following LPS and MAA stimulation in vitro. Also, these results suggest that halothane exposure may increase the risk of alcohol-induced solid organ injury secondary to TNF-induced inflammation. Other investigators have reported similar proinflammatory cytokine release with other (isoflurane and sevoflurane) inhaled anesthetic exposure, suggesting inhaled anesthetics should be used with caution in alcohol consuming humans.},
 year = {2013}
}

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TY  - JOUR
T1  - A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation
AU  - Gary E Hill
AU  - Irina Gasanova
AU  - Geoffrey M Thiele
Y1  - 2013/12/20
PY  - 2013
N1  - https://doi.org/10.11648/j.ja.20140201.11
DO  - 10.11648/j.ja.20140201.11
T2  - International Journal of Anesthesia and Clinical Medicine
JF  - International Journal of Anesthesia and Clinical Medicine
JO  - International Journal of Anesthesia and Clinical Medicine
SP  - 1
EP  - 7
PB  - Science Publishing Group
SN  - 2997-2698
UR  - https://doi.org/10.11648/j.ja.20140201.11
AB  - Background: Inhaled anesthetics, including halothane, iso- and sevoflurane induce proinflammatory cytokine release. Halothane is an inhaled anesthetic agent that is metabolized by the liver into a highly reactive product, trifluoroacetyl chloride, which can react endogenously to form a trifluoroacetyl-adduct (TFA-adduct). The MAA-adduct is formed by acetaldehyde and malondialdehyde reacting with endogenous proteins and is  found in both patients and animals post-consumption of alcohol. These TFA and MAA-adducts have been shown to cause the release of proinflammatory cytokines by endogenous inflammatory cells. If both adducts share a similar mechanism of cell activation, receiving general anesthesia following alcohol ingestion could exacerbate the inflammatory response caused by the inhaled general anesthetic halothane and lead to solid organ (including liver and brain) injury. Methods: Control diet and alcohol-fed rats were randomized to receive halothane pretreatments by intraperitoneal injection mixed in sesame oil. Following the intraperitoneal injections, 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 determined. Results: Halothane pre-treated rat HECs demonstrated 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 groups. Conclusion: These results demonstrate that halothane and MAA-adduct pre-treatment will increase the inflammatory response (TNF-α release) in rat HECs following LPS and MAA stimulation in vitro. Also, these results suggest that halothane exposure may increase the risk of alcohol-induced solid organ injury secondary to TNF-induced inflammation. Other investigators have reported similar proinflammatory cytokine release with other (isoflurane and sevoflurane) inhaled anesthetic exposure, suggesting inhaled anesthetics should be used with caution in alcohol consuming humans.
VL  - 2
IS  - 1
ER  -

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Author Information

Gary E Hill

Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, TX, USA
Irina Gasanova

Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, TX, USA
Geoffrey M Thiele

Veterans Administration Alcohol Research Center, Omaha Veterans Administration Medical Center, Woolworth Avenue, Omaha, NE

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Gary E Hill, Irina Gasanova, Geoffrey M Thiele. (2013). A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation. International Journal of Anesthesia and Clinical Medicine, 2(1), 1-7. https://doi.org/10.11648/j.ja.20140201.11

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Gary E Hill; Irina Gasanova; Geoffrey M Thiele. A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation. Int. J. Anesth. Clin. Med. 2013, 2(1), 1-7. doi: 10.11648/j.ja.20140201.11

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AMA Style

Gary E Hill, Irina Gasanova, Geoffrey M Thiele. A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation. Int J Anesth Clin Med. 2013;2(1):1-7. doi: 10.11648/j.ja.20140201.11

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@article{10.11648/j.ja.20140201.11,
  author = {Gary E Hill and Irina Gasanova and Geoffrey M Thiele},
  title = {A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation},
  journal = {International Journal of Anesthesia and Clinical Medicine},
  volume = {2},
  number = {1},
  pages = {1-7},
  doi = {10.11648/j.ja.20140201.11},
  url = {https://doi.org/10.11648/j.ja.20140201.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ja.20140201.11},
  abstract = {Background: Inhaled anesthetics, including halothane, iso- and sevoflurane induce proinflammatory cytokine release. Halothane is an inhaled anesthetic agent that is metabolized by the liver into a highly reactive product, trifluoroacetyl chloride, which can react endogenously to form a trifluoroacetyl-adduct (TFA-adduct). The MAA-adduct is formed by acetaldehyde and malondialdehyde reacting with endogenous proteins and is  found in both patients and animals post-consumption of alcohol. These TFA and MAA-adducts have been shown to cause the release of proinflammatory cytokines by endogenous inflammatory cells. If both adducts share a similar mechanism of cell activation, receiving general anesthesia following alcohol ingestion could exacerbate the inflammatory response caused by the inhaled general anesthetic halothane and lead to solid organ (including liver and brain) injury. Methods: Control diet and alcohol-fed rats were randomized to receive halothane pretreatments by intraperitoneal injection mixed in sesame oil. Following the intraperitoneal injections, 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 determined. Results: Halothane pre-treated rat HECs demonstrated 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 groups. Conclusion: These results demonstrate that halothane and MAA-adduct pre-treatment will increase the inflammatory response (TNF-α release) in rat HECs following LPS and MAA stimulation in vitro. Also, these results suggest that halothane exposure may increase the risk of alcohol-induced solid organ injury secondary to TNF-induced inflammation. Other investigators have reported similar proinflammatory cytokine release with other (isoflurane and sevoflurane) inhaled anesthetic exposure, suggesting inhaled anesthetics should be used with caution in alcohol consuming humans.},
 year = {2013}
}

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TY  - JOUR
T1  - A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation
AU  - Gary E Hill
AU  - Irina Gasanova
AU  - Geoffrey M Thiele
Y1  - 2013/12/20
PY  - 2013
N1  - https://doi.org/10.11648/j.ja.20140201.11
DO  - 10.11648/j.ja.20140201.11
T2  - International Journal of Anesthesia and Clinical Medicine
JF  - International Journal of Anesthesia and Clinical Medicine
JO  - International Journal of Anesthesia and Clinical Medicine
SP  - 1
EP  - 7
PB  - Science Publishing Group
SN  - 2997-2698
UR  - https://doi.org/10.11648/j.ja.20140201.11
AB  - Background: Inhaled anesthetics, including halothane, iso- and sevoflurane induce proinflammatory cytokine release. Halothane is an inhaled anesthetic agent that is metabolized by the liver into a highly reactive product, trifluoroacetyl chloride, which can react endogenously to form a trifluoroacetyl-adduct (TFA-adduct). The MAA-adduct is formed by acetaldehyde and malondialdehyde reacting with endogenous proteins and is  found in both patients and animals post-consumption of alcohol. These TFA and MAA-adducts have been shown to cause the release of proinflammatory cytokines by endogenous inflammatory cells. If both adducts share a similar mechanism of cell activation, receiving general anesthesia following alcohol ingestion could exacerbate the inflammatory response caused by the inhaled general anesthetic halothane and lead to solid organ (including liver and brain) injury. Methods: Control diet and alcohol-fed rats were randomized to receive halothane pretreatments by intraperitoneal injection mixed in sesame oil. Following the intraperitoneal injections, 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 determined. Results: Halothane pre-treated rat HECs demonstrated 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 groups. Conclusion: These results demonstrate that halothane and MAA-adduct pre-treatment will increase the inflammatory response (TNF-α release) in rat HECs following LPS and MAA stimulation in vitro. Also, these results suggest that halothane exposure may increase the risk of alcohol-induced solid organ injury secondary to TNF-induced inflammation. Other investigators have reported similar proinflammatory cytokine release with other (isoflurane and sevoflurane) inhaled anesthetic exposure, suggesting inhaled anesthetics should be used with caution in alcohol consuming humans.
VL  - 2
IS  - 1
ER  -

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