Mitochondrial Injury in Human Acute Carbon Monoxide Poisoning: The Effect of Oxygen Treatment

Abstract

The best oxygen therapy for acute carbon monoxide poisoning (ACOP) remains unestablished. Reported mitochondrial complex IV (mtCIV) inhibition, together with carboxyhaemoglobin (COHb)-induced hypoxia, may influence acute clinical symptoms and outcome. To “mitochondrially” evaluate treatment efficacy, we correlated intoxication severity and symptoms with mitochondrial function (mtCIV activity) and oxidative stress (lipid peroxidation) in 60 poisoned patients and determined ACOP recovery depending on either normobaric or hyperbaric oxygen therapy along a 3-month follow-up. In the present article we positively evaluate mtCIV as a good marker of ACOP recovery, treatment effectiveness, and late neurological syndrome development, which advocates for hyperbaric oxygen therapy as the treatment of choice. However, we discourage its usefulness as a severity marker because of its excessive sensitivity. We additionally evaluate oxidative stress role and prognostic factors for neurological sequelae development.

Keywords:

• Mitochondrial toxicity
• carbon monoxide (CO)
• hyperbaric oxygen treatment (HBO)
• normobaric oxygen treatment (NBO)
• cytochrome c oxidase (COX) or mitochondrial complex IV (mtCIV)
• oxidative stress (lipid peroxidation)
• late neurological syndrome (LNS)

Acknowledgments

Standard and non-standard abbreviations: carbon monoxide (CO), carboxyhaemoglobin (COHb), acute carbon monoxide poisoning (ACOP), moderate and severe acute carbon monoxide poisoned patients (MCOP and SCOP), normobaric and hyperbaric oxygen (NBO and HBO), severe acute carbon monoxide intoxicated patients treated with one or two hyperbaric oxygen sessions (SHBO1 or SHBO2), moderate acute carbon monoxide poisoned patients treated with normobaric oxygen or one session of hyperbaric oxygen (MNBO or MHBO), late neurological syndrome (LNS), mitochondrial complex IV (mtCIV) or cytochrome c oxidase (COX), citrate synthase (CS), malondialdehyde (MDA) and 4-hydroxyalkenal (HAE), reactive oxygen species (ROS), peripheral blood mononuclear cells (PMBC) and standard error of the mean (SEM).This work has been supported by Fondo de Investigaciones Sanitarias [FIS 0229/08]; Suports a Grups de Recerca de la Generalitat de Catalunya [2009/SGR/1158] and the CIBER de Enfermedades Raras (CIBERER, an initiative of ISCIII).